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8132019 Cervical Excizional Treatement of Young Women
Walter Kinney a William C Hunt b Helen Dinkelspiel c Michael Robertson b Jack Cuzick d Cosette M Wheeler be For The New Mexico HPV Pap Registry Steering Committeea Department of Womens Health and Division of Gynecologic Oncology The Permanente Medical Group Oakland CA USAb Department of Pathology University of New Mexico Health Sciences Center Albuquerque NM USAc Division of Gynecologic Oncology Columbia University College of Physicians and Surgeons New York NY USAd Wolfson Institute of Preventive Medicine Queen Mary University of London London UK e Department of Obstetrics and Gynecology University of New Mexico Health Sciences Center Albuquerque NM USA
H I G H L I G H T S
bull Biopsies of bCIN2 with HSIL cytology carried as much risk for CIN3+ on LEEP as did CIN2 with HSIL cytology
bull CIN2 and cytology bHSIL preceded more LEEPs than any other combination in every age group studied
bull The opportunity to reduce excisional harm will be lost if CIN3 and CIN2 are merged into a single histologic category
a b s t r a c ta r t i c l e i n f o
Article history
Received 1 October 2013
Accepted 26 December 2013
Available online xxxx
Keywords
Cervical screening
Colposcopy
Loop electrosurgical excision procedure (LEEP)
Cervical intraepithelial neoplasia grades 2
and 3 (CIN2 and CIN3)
Adherence to cervical treatment guidelines
Effectiveness and harms of cervical screening
Objective Assessment of cytology and biopsy results preceding cervical excisional treatment and their
association with excisional histology to evaluate compliancewith treatment recommendationsand the potential
effect of revisions in cervical histology terminology and usage
Method Datafrom a unique statewide population-based screening registrywas used to describe theuse andhis-
tologic outcomes of cervical excisional procedures in the year following an abnormal cervical screening cytologyResults From 2007 to 2011 LEEP rates decreased 87 45 and 16 for women aged 15 ndash20 21ndash24 and
25ndash29 years respectively Reductions were attributable to an overall decline in cervical screening and colposcopy
anda decreasein LEEP followinga diagnosisof less than cervical intraepithelial neoplasia grade 2 (bCIN2) or CIN2
histologypreceded by any abnormalcytology other than high-grade squamous intraepithelial lesion (bHSIL) LEEP
rates did not change signi1047297cantly (p N 07) for women aged 30ndash39 years Irrespective of age CIN2 was the most
common histologic antecedent of excisional treatment (42) with most (80) preceded by bHSIL cytology
Conclusion Cervical excisions are an unavoidable consequence of cervical screening Adherence to treatment
guidelines stipulating conservative follow-up of young women with biopsies leCIN2 could signi1047297cantly decrease
the number of excisional procedures and associated harms This opportunity will be lost if cervical intraepithelial
neoplasiagrade3 (CIN3) andsome or all of CIN2 aremerged into a singlehistologic categoryas hasbeen recently
recommended in the United States
copy 2013 The Authors Published by Elsevier Inc All rights reserved
Introduction
In March 2012 the United States Preventive Services Task Force
(USPSTF) the American Cancer Society (ACS) the American Society for
Colposcopy and Clinical Pathology (ASCCP) and the American Society
forClinical Pathology (ASCP) released newguidelines recommendingcer-
vical screening at three-year intervals starting at age 21 with the option
to substitute cytology plus human papillomavirus (HPV) DNA testing
(ldquocotestingrdquo) at 1047297ve-year intervals starting at the age of 30 The cotesting
regimen was preferred for women aged 30 years and above by all groups
except the USPSTF [1 2]
Gynecologic Oncology xxx (2014) xxxndashxxx
This is an open-access article distributed under the terms of the Creative Commons
Attribution-NonCommercial-No Derivative Works License which permits non-commercial
use distribution and reproduction in any medium provided the original author and source
are credited Condensation Adherence to treatment guidelines stipulating conservative follow-
up of youngwomenwithbiopsies leCIN2 could signi1047297cantlydecreasethe numberof exci-
sional procedures
Corresponding author at Departments of Pathology and Obstetrics and Gynecology
House of Prevention Epidemiology MSC 02-1670 Bldg 191 1816 Sigma Chi Rd NE
University of New Mexico Health Sciences Center Albuquerque NM 87131 USA Fax
+1 505 277 0265
E-mail address cwheelersaludunmedu (CM Wheeler)
YGYNO-975325 No of pages 8 4C 4 5
0090-8258$ ndash see front matter copy 2013 The Authors Published by Elsevier Inc All rights reserved
httpdxdoiorg101016jygyno201312037
Contents lists available at ScienceDirect
Gynecologic Oncology
j o u r n a l h o m e p a g e w w w e l s e v i e r c o m l o c a t e y g y n o
Please cite this article asKinneyW et alCervical excisional treatment of young womenA population-based study Gynecol Oncol (2014)http dxdoiorg101016jygyno201312037
8132019 Cervical Excizional Treatement of Young Women
intraepithelial lesion (LSIL) atypical squamous cells-cannot rule out
high-grade (ASC-H) atypical glandular cells (AGC) and high-grade
intraepithelial lesion (HSIL) and less than HSIL (bHSIL) which included
ASC-US ASC-US+ LSIL ASC-H and AGC Cytologic results of carcinoma
were classi1047297ed as HSIL The HPVstatus of ASC-USresultswas determined
by linking the index cytology with a separate database of HPV tests
Cervical biopsy results were classi1047297ed as negative cervicalintraepithelial neoplasiagrades 1 2 and3 (CIN1 CIN2 CIN3)carcinoma
in situ (CIS) adenocarcinoma in situ (AIS) and cancer The histologic
interpretation CIN1ndash2 is included with CIN2 and CIN2ndash3 is included
with CIN3 This is believed to represent current clinical practice provides
the most charitable view of the indications for excisional treatment and
recognizes the reportedirreproducibility of these histologic designations
though it is understood that there is at present no published data about
subsequent cancer risk to validate these choices
We also computed population rates of cervical excision for the
period 2007ndash2011 These rates were computed as the number of
women treated in a given calendar year per 10000 women in the
population and also per 10000 women receiving a screening cervical
cytology test New Mexico population counts are US Census estimates
(wwwcensusgov) Using the 2007ndash2010 Centers for Disease Controlbridged-race population 1047297les 422 of NM women were non-Hispanic
white 422 were Hispanic white 30 were African American 105
were American Indian and 19 were Asian
Data analysis was conducted using SAS version 93 Con1047297dence
intervals for population excisional treatment rates are based on normal
approximation and all con1047297dence intervals for proportions are exact
Signi1047297cance testing with the CochranndashArmitage test of linear trend
was employed to discern changes over time
Results
The rate of excisional treatmentfor cervical abnormalities decreased
in New Mexico over the period 2007ndash2011 for women b30 years of age
(Table 1) The decrease was greatest for women aged 15ndash
20 years
2 W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx
Pleasecite this article as KinneyW et al Cervical excisional treatment of young womenA population-based study Gynecol Oncol (2014) http dxdoiorg101016jygyno201312037
8132019 Cervical Excizional Treatement of Young Women
a p-Values are for test of trend in rates over the 1047297ve year period
3W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx
Please cite this article asKinneyW et alCervical excisional treatment of young womenA population-based study Gynecol Oncol (2014)http dxdoiorg101016jygyno201312037
8132019 Cervical Excizional Treatement of Young Women
a Follow-up classi1047297cation is hierarchical colposcopy with cervical biopsyor endocervical curettage (ECC)else othergynecologic procedure else follow-up cytology else no follow-up
Colposcopywithout biopsyor curettage is notascertainedby theNew MexicoHPV PapRegistry(NMHPVPR) Womenwith LEEP andno precedingcolposcopy areincluded in thecolpos-
copy category Other gynecologic procedures include endometrial vaginal and vulvar biopsies and hysterectomies Follow-up cytology is de1047297ned as cervical cytology within 300 days of
the index cytology Cytologic results are as follows atypical squamous cells of unknown signi1047297cance (ASC-US) is negative for high-risk human papillomavirus (HPV) or HPV status un-knownASC-US+ is positive forhigh-risk HPVde1047297nedas positive forone or more HPVtypes including16 18 3133 35 3945 51 52 56 5859 and68 low-gradeintraepitheliallesion
(LSIL) atypical squamous cells-cannot rule out high-grade (ASC-H) atypical glandular cells (AGC) and high-grade intraepithelial lesion (HSIL)
Fig 1 Percent of women with colposcopic biopsy or endocervical curettage (ECC) within
12 months of abnormal index screeningcytology by ageof woman andresultof cytology
Cytology results are classi1047297ed as ASC-US [atypical squamous cells of undetermined
signi1047297cance negative for high-risk humanpapillomavirus (HPV)or HPV statusunknown]
ASC-US+ [ASC-US positive for high-risk HPV] LSIL [low-grade squamous intraepithelial
lesion] ASC-H[atypical squamous cells-cannot rule out high-grade] and HSIL [high-grade
squamous intraepithelial lesion]
4 W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx
Pleasecite this article as KinneyW et al Cervical excisional treatment of young womenA population-based study Gynecol Oncol (2014) http dxdoiorg101016jygyno201312037
8132019 Cervical Excizional Treatement of Young Women
AlthoughLEEPSperformed within1 year of theindexcytologyaccounted forthe majority (70) some women received LEEP treatment more than 1 year after theindexcytology In the
secondyear followingthe index cytologythe percent of womenreceiving LEEP increased from 352 at 12 monthsto 39at 24 monthsfor HSIL cytologyfrom 179 to 211 forASC-H
from 53 to 67 for ASC-US+ [high-risk HPV positive] and LSIL combined from 96 to 112 for AGC and from 05 to 11 for ASC-US [high-risk HPV negative or unknown]a Histology resultis themost severediagnosis from anycervicalbiopsyor ECCdone after theindex cytology andbefore theLEEP Cytology result is themost severediagnosis from the
index cytology and any follow-upcytology done before LEEP Cervical intraepithelial neoplasia grade3 (CIN3+) includes CIN3 CIN grades 2ndash3 (CIN2ndash3) carcinoma in situ (CIS) adeno-
carcinoma in situ (AIS) and cancer cervical intraepithelial neoplasia grade 2 (CIN2) includes CIN2 and CIN grades 1ndash2 (CIN1ndash2) abbreviations for cytologic results are as outlined in
Table 2 less than high-grade squamous intraepithelial lesions (bHSIL) cytology includes ASC-US ASC-US+ LSIL ASC-H and AGC
6 W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx
Pleasecite this article as KinneyW et al Cervical excisional treatment of young womenA population-based study Gynecol Oncol (2014) http dxdoiorg101016jygyno201312037
8132019 Cervical Excizional Treatement of Young Women
implemented (ie CIN2 and CIN3 are grouped as ldquohigh-graderdquo with the
speci1047297cation of CIN grade being optional) then reduction of the potential
harms associated with screening women in their childbearing years can
only be realized by decreasing screening itself rather than encouraging
more appropriate responses to the lesser histologic abnormalities that
precede the majority of LEEPs in the youngest women
Con1047298icts of interest statement
The authors report no con1047298icts of interest
Acknowledgments
Evaluations reported in this publication were funded by the US
National Institute of Allergy and Infectious Diseases (NIAID) and the
US National Cancer Institute (NCI) under cooperative agreements
U19AI084081 and U54CA164336 to CMW The NIAID and NCI had no
role in the study design in the collection analysis and interpretation
of data in the writing of the report and in the decision to submit
the paper for publication The content is solely the responsibility of
the authors and does not necessarily represent the of 1047297cial views of
the US National Institutes of Health The authors had full access to the
data and had 1047297nal responsibility for the decision to submit for publica-
tion The authors (WC WCH HD MR JC and CMW) had access to thedata reviewed provided input and approved the 1047297nal manuscript
submitted for publication Walter Kinney MD and Cosette Wheeler
PhD created the concept of the manuscript Walter Kinney MD and
Helen Dinkelspiel MD wrote the manuscript that was reviewed
and modi1047297ed by all authors William C Hunt performed the data extrac-
tion and analyses Members of the New Mexico HPV Pap Registry
(NMHPVPR) Steering Committee gave input to the manuscript concepts
and supported the directions of the NMHPVPR including the evaluations
presented in this manuscript The NMHPVPR Steering members partici-
pating are as follows Nancy E Joste MD University of New Mexico
Health SciencesCenter and Tricore Reference Laboratories Albuquerque
New Mexico Walter Kinney MD Kaiser Permanente Northern
California Cosette M Wheeler PhD University of New Mexico Health
Sciences Center William C Hunt MS University of New Mexico Health
Sciences Center Deborah Thompson MD MSPH New Mexico Depart-
ment of Health Susan Baum MD MPH New Mexico Department of
Health Linda Gorgos MD MSc former Medical Director of the Infectious
Disease Bureau New Mexico Department of Health Alan Waxman MD
MPH University of New Mexico Health Sciences Center David Espey
MD US Centers for Disease Control and Prevention Jane McGrath MD
University of New Mexico Health Sciences Center Steven Jenison MD
Community Member Mark Schiffman MD MPH US National Cancer
Institute Philip Castle PhD MPH Albert Einstein College of MedicineVicki Benard PhDUS Centers for Disease Control and Prevention Debbie
Saslow PhD American Cancer Society Jane J Kim PhD Harvard School
of Public Health Mark H Stoler MD University of Virginia Jack Cuzick
PhD Wolfson Institute of Preventive Medicine London Giovanna Rossi
Pressley MSc Collective Action Strategies and RWJF Center for Health
Policy at University of New Mexico and Kevin English RPh MPH
Albuquerque Area Southwest Tribal Epidemiology Center (AASTEC) No
compensation was received for contributions to this manuscript by any
named authors or by the NMHPVPR Steering Committee members
References
[1] Saslow D Soloman D Lawson HW Killackey M Kulasingam SL Cain J et alAmerican Cancer Society American Society for Colposcopy and Cervical Pathologyand American Society for Clinical Pathology screening guidelines for the preventionand early detection of cervical cancer CA Cancer J Clin 201262147ndash72
[2] Moyer VA USPreventive ServicesTaskForce Screeningfor cervical cancer USpreven-tive services taskforce recommendation statement Ann InternMed 2012156880ndash91
[3] ACOG Committee on Practice BulletinsmdashGynecology ACOG Practice Bulletin no 109cervical cytology screening Obstet Gynecol 20091141409ndash20
[4] American College of Obstetricians and Gynecologists ACOG Committee Opinion No463 cervical cancer in adolescents screening evaluation and management ObstetGynecol 2010116469ndash72
[5] Moscicki AB Cox JT Practice improvement in cervical screening and management(PICSM) symposium on management of cervical abnormalities in adolescents andyoung women J Low Genit Tract Dis 20101473ndash80
[6] Sasieni P Castanon A Cuzick J Effectiveness of cervical screening with age popula-tion based casendashcontrol study of prospectively recorded data BMJ 2009339b2968[Erratum in BMJ 2009 339b3115]
[7] Moscicki AB Ma Y Wibbelsman C et al Rate of and risks for regression of cervicalintraepithelial neoplasia 2 in adolescents and young women Obstet Gynecol
20101161373ndash
80
Table 4
Time trends in percent of abnormal index cytology followed by a LEEP within 1 yeara
a Histologyresult is themost severe diagnosis from anycervicalbiopsyor ECCdone after theindex cytologyand beforethe LEEP Cytology result is themost severe diagnosis from the
indexcytologyand any follow-up cytology donebefore LEEPAbbreviations are as detailed for Table 3 CIN3+ includes CIN3 CIN2ndash3 CIS AIS andcancerCIN2 includes CIN2 andCIN1ndash2
bHSIL cytology includes ASC-US ASC-US+ LSIL ASC-H and AGC
7W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx
Please cite this article asKinneyW et alCervical excisional treatment of young womenA population-based study Gynecol Oncol (2014)http dxdoiorg101016jygyno201312037
8132019 Cervical Excizional Treatement of Young Women
[8] Wright Jr TC Massad LS Dunton CJ Spitzer M Wilkinson EJ Solomon D 2006ASCCP-Sponsored Consensus Conference 2006 consensus guidelines for the man-agement of women with abnormal cervical screening tests J Low Genit Tract Dis200711201ndash22 [Erratum in J Low Genit Tract Dis 2008 12 255]
[9] Kyrgiou M Koliopoulos G Martin-Hirsch P Arbyn M Prendiville WParaskevaidis E Obstetric outcomes after conservative treatment forintraepithelial or early invasive cervical lesions systematic review and meta-analysis Lancet 2006367489ndash98
[10] Sadler L Saftlas A Wang W Exeter M Whittaker J McCowan L Treatmentfor cervical intraepithelial neoplasia and risk of preterm delivery JAMA20042912100ndash6
[11] Samson SL Bentley JR Fahey TJ McKay DJ Gill GH The effect of loop electro-surgical excision procedure on future pregnancy outcome Obstet Gynecol2005105325ndash32
[12] Yabroff KRSaraiya M Meissner HI HaggstromDA Wideroff L Yuan G et al Special-ty differences in primary care physician reports of Papanicolaou test screeningpractices a national survey 2006 to 2007 Ann Intern Med 2009151602ndash11
[13] Lee JW Berkowitz Z Saraiya M Low-risk human papillomavirus testing and othernonrecommended human papillomavirus testing practices among US health careproviders Obstet Gynecol 20111184ndash13
[14] Roland KB Soman A Benard VB Saraiya M Human papillomavirus and Papanicolaoutests screening interval recommendations in the United States Am J Obstet Gynecol2011205447e1ndash8
[15] Saraiya M Berkowitz Z Yabroff KR Wideroff L Kobrin S Benard V Cervical cancerscreening with both human papillomavirus and Papanicolaou testing vsPapanicolaou testing alone what screeningintervals are physicians recommendingArch Intern Med 2010170977ndash85
[16] Wheeler CM Hunt WC Cuzick J et al A population-based study of human papillo-mavirus genotype prevalence in the United States baseline measures prior tomass human papillomavirus vaccination Int J Cancer Jan 1 2013132(1)198ndash207
[17] CastlePE SchiffmanM Wheeler CMSolomon D Evidence forfrequent regression of cervical intraepithelial neoplasia-grade 2 Obstet Gynecol 200911318ndash25
[18] Robertson AJ Anderson JM Beck JS et al Observer variability in histopathologicalreporting of cervical biopsy specimens J Clin Pathol 198942231ndash8
[19] Wright Jr TC MassadLS DuntonCJ SpitzerM Wilkinson EJSolomonD 2006AmericanSociety for Colposcopy and Cervical Pathology-sponsored Consensus Conference 2006consensus guidelines for the management of women with cervical intraepithelialneoplasia or adenocarcinoma in situ J Low Genit Tract Dis 200711223ndash39
[20] Pretorius RG Zhang WH Belinson JL et al Colposcopically directed biopsy randomcervical biopsy and endocervical curettage in the diagnosis of cervical intraepithelialneoplasia II or worse Am J Obstet Gynecol 2004191430ndash4
[21] Stoler MH Vichnin MD Ferenczy A et al FUTURE I II and III Investigators Theaccuracy of colposcopic biopsy analyses from the placebo arm of the Gardasilclinical trials Int J Cancer 20111281354ndash62
[22] Cox JT More questions about the accuracy of colposcopy what does this mean forcervical cancer prevention Obstet Gynecol 20081111266ndash7
[23] Pretorius RG Belinson JL Burchette RJ Hu S Zhang X Qiao YL Regardless of skillperforming more biopsies increases the sensitivity of colposcopy J Low GenitTract Dis 201115180ndash8
[24] Darragh TM Colgan TJ Cox JT et al LAST Project Work Groups The LowerAnogenital Squamous Terminology Standardization Project for HPV-Associated Le-sions background and consensus recommendations from the College of AmericanPathologists and the American Society for Colposcopy and Cervical Pathology JLow Genit Tract Dis 201216205ndash42
8 W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx
Pleasecite this article as KinneyW et al Cervical excisional treatment of young womenA population-based study Gynecol Oncol (2014) http dxdoiorg101016jygyno201312037
8132019 Cervical Excizional Treatement of Young Women
intraepithelial lesion (LSIL) atypical squamous cells-cannot rule out
high-grade (ASC-H) atypical glandular cells (AGC) and high-grade
intraepithelial lesion (HSIL) and less than HSIL (bHSIL) which included
ASC-US ASC-US+ LSIL ASC-H and AGC Cytologic results of carcinoma
were classi1047297ed as HSIL The HPVstatus of ASC-USresultswas determined
by linking the index cytology with a separate database of HPV tests
Cervical biopsy results were classi1047297ed as negative cervicalintraepithelial neoplasiagrades 1 2 and3 (CIN1 CIN2 CIN3)carcinoma
in situ (CIS) adenocarcinoma in situ (AIS) and cancer The histologic
interpretation CIN1ndash2 is included with CIN2 and CIN2ndash3 is included
with CIN3 This is believed to represent current clinical practice provides
the most charitable view of the indications for excisional treatment and
recognizes the reportedirreproducibility of these histologic designations
though it is understood that there is at present no published data about
subsequent cancer risk to validate these choices
We also computed population rates of cervical excision for the
period 2007ndash2011 These rates were computed as the number of
women treated in a given calendar year per 10000 women in the
population and also per 10000 women receiving a screening cervical
cytology test New Mexico population counts are US Census estimates
(wwwcensusgov) Using the 2007ndash2010 Centers for Disease Controlbridged-race population 1047297les 422 of NM women were non-Hispanic
white 422 were Hispanic white 30 were African American 105
were American Indian and 19 were Asian
Data analysis was conducted using SAS version 93 Con1047297dence
intervals for population excisional treatment rates are based on normal
approximation and all con1047297dence intervals for proportions are exact
Signi1047297cance testing with the CochranndashArmitage test of linear trend
was employed to discern changes over time
Results
The rate of excisional treatmentfor cervical abnormalities decreased
in New Mexico over the period 2007ndash2011 for women b30 years of age
(Table 1) The decrease was greatest for women aged 15ndash
20 years
2 W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx
Pleasecite this article as KinneyW et al Cervical excisional treatment of young womenA population-based study Gynecol Oncol (2014) http dxdoiorg101016jygyno201312037
8132019 Cervical Excizional Treatement of Young Women
a p-Values are for test of trend in rates over the 1047297ve year period
3W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx
Please cite this article asKinneyW et alCervical excisional treatment of young womenA population-based study Gynecol Oncol (2014)http dxdoiorg101016jygyno201312037
8132019 Cervical Excizional Treatement of Young Women
a Follow-up classi1047297cation is hierarchical colposcopy with cervical biopsyor endocervical curettage (ECC)else othergynecologic procedure else follow-up cytology else no follow-up
Colposcopywithout biopsyor curettage is notascertainedby theNew MexicoHPV PapRegistry(NMHPVPR) Womenwith LEEP andno precedingcolposcopy areincluded in thecolpos-
copy category Other gynecologic procedures include endometrial vaginal and vulvar biopsies and hysterectomies Follow-up cytology is de1047297ned as cervical cytology within 300 days of
the index cytology Cytologic results are as follows atypical squamous cells of unknown signi1047297cance (ASC-US) is negative for high-risk human papillomavirus (HPV) or HPV status un-knownASC-US+ is positive forhigh-risk HPVde1047297nedas positive forone or more HPVtypes including16 18 3133 35 3945 51 52 56 5859 and68 low-gradeintraepitheliallesion
(LSIL) atypical squamous cells-cannot rule out high-grade (ASC-H) atypical glandular cells (AGC) and high-grade intraepithelial lesion (HSIL)
Fig 1 Percent of women with colposcopic biopsy or endocervical curettage (ECC) within
12 months of abnormal index screeningcytology by ageof woman andresultof cytology
Cytology results are classi1047297ed as ASC-US [atypical squamous cells of undetermined
signi1047297cance negative for high-risk humanpapillomavirus (HPV)or HPV statusunknown]
ASC-US+ [ASC-US positive for high-risk HPV] LSIL [low-grade squamous intraepithelial
lesion] ASC-H[atypical squamous cells-cannot rule out high-grade] and HSIL [high-grade
squamous intraepithelial lesion]
4 W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx
Pleasecite this article as KinneyW et al Cervical excisional treatment of young womenA population-based study Gynecol Oncol (2014) http dxdoiorg101016jygyno201312037
8132019 Cervical Excizional Treatement of Young Women
AlthoughLEEPSperformed within1 year of theindexcytologyaccounted forthe majority (70) some women received LEEP treatment more than 1 year after theindexcytology In the
secondyear followingthe index cytologythe percent of womenreceiving LEEP increased from 352 at 12 monthsto 39at 24 monthsfor HSIL cytologyfrom 179 to 211 forASC-H
from 53 to 67 for ASC-US+ [high-risk HPV positive] and LSIL combined from 96 to 112 for AGC and from 05 to 11 for ASC-US [high-risk HPV negative or unknown]a Histology resultis themost severediagnosis from anycervicalbiopsyor ECCdone after theindex cytology andbefore theLEEP Cytology result is themost severediagnosis from the
index cytology and any follow-upcytology done before LEEP Cervical intraepithelial neoplasia grade3 (CIN3+) includes CIN3 CIN grades 2ndash3 (CIN2ndash3) carcinoma in situ (CIS) adeno-
carcinoma in situ (AIS) and cancer cervical intraepithelial neoplasia grade 2 (CIN2) includes CIN2 and CIN grades 1ndash2 (CIN1ndash2) abbreviations for cytologic results are as outlined in
Table 2 less than high-grade squamous intraepithelial lesions (bHSIL) cytology includes ASC-US ASC-US+ LSIL ASC-H and AGC
6 W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx
Pleasecite this article as KinneyW et al Cervical excisional treatment of young womenA population-based study Gynecol Oncol (2014) http dxdoiorg101016jygyno201312037
8132019 Cervical Excizional Treatement of Young Women
implemented (ie CIN2 and CIN3 are grouped as ldquohigh-graderdquo with the
speci1047297cation of CIN grade being optional) then reduction of the potential
harms associated with screening women in their childbearing years can
only be realized by decreasing screening itself rather than encouraging
more appropriate responses to the lesser histologic abnormalities that
precede the majority of LEEPs in the youngest women
Con1047298icts of interest statement
The authors report no con1047298icts of interest
Acknowledgments
Evaluations reported in this publication were funded by the US
National Institute of Allergy and Infectious Diseases (NIAID) and the
US National Cancer Institute (NCI) under cooperative agreements
U19AI084081 and U54CA164336 to CMW The NIAID and NCI had no
role in the study design in the collection analysis and interpretation
of data in the writing of the report and in the decision to submit
the paper for publication The content is solely the responsibility of
the authors and does not necessarily represent the of 1047297cial views of
the US National Institutes of Health The authors had full access to the
data and had 1047297nal responsibility for the decision to submit for publica-
tion The authors (WC WCH HD MR JC and CMW) had access to thedata reviewed provided input and approved the 1047297nal manuscript
submitted for publication Walter Kinney MD and Cosette Wheeler
PhD created the concept of the manuscript Walter Kinney MD and
Helen Dinkelspiel MD wrote the manuscript that was reviewed
and modi1047297ed by all authors William C Hunt performed the data extrac-
tion and analyses Members of the New Mexico HPV Pap Registry
(NMHPVPR) Steering Committee gave input to the manuscript concepts
and supported the directions of the NMHPVPR including the evaluations
presented in this manuscript The NMHPVPR Steering members partici-
pating are as follows Nancy E Joste MD University of New Mexico
Health SciencesCenter and Tricore Reference Laboratories Albuquerque
New Mexico Walter Kinney MD Kaiser Permanente Northern
California Cosette M Wheeler PhD University of New Mexico Health
Sciences Center William C Hunt MS University of New Mexico Health
Sciences Center Deborah Thompson MD MSPH New Mexico Depart-
ment of Health Susan Baum MD MPH New Mexico Department of
Health Linda Gorgos MD MSc former Medical Director of the Infectious
Disease Bureau New Mexico Department of Health Alan Waxman MD
MPH University of New Mexico Health Sciences Center David Espey
MD US Centers for Disease Control and Prevention Jane McGrath MD
University of New Mexico Health Sciences Center Steven Jenison MD
Community Member Mark Schiffman MD MPH US National Cancer
Institute Philip Castle PhD MPH Albert Einstein College of MedicineVicki Benard PhDUS Centers for Disease Control and Prevention Debbie
Saslow PhD American Cancer Society Jane J Kim PhD Harvard School
of Public Health Mark H Stoler MD University of Virginia Jack Cuzick
PhD Wolfson Institute of Preventive Medicine London Giovanna Rossi
Pressley MSc Collective Action Strategies and RWJF Center for Health
Policy at University of New Mexico and Kevin English RPh MPH
Albuquerque Area Southwest Tribal Epidemiology Center (AASTEC) No
compensation was received for contributions to this manuscript by any
named authors or by the NMHPVPR Steering Committee members
References
[1] Saslow D Soloman D Lawson HW Killackey M Kulasingam SL Cain J et alAmerican Cancer Society American Society for Colposcopy and Cervical Pathologyand American Society for Clinical Pathology screening guidelines for the preventionand early detection of cervical cancer CA Cancer J Clin 201262147ndash72
[2] Moyer VA USPreventive ServicesTaskForce Screeningfor cervical cancer USpreven-tive services taskforce recommendation statement Ann InternMed 2012156880ndash91
[3] ACOG Committee on Practice BulletinsmdashGynecology ACOG Practice Bulletin no 109cervical cytology screening Obstet Gynecol 20091141409ndash20
[4] American College of Obstetricians and Gynecologists ACOG Committee Opinion No463 cervical cancer in adolescents screening evaluation and management ObstetGynecol 2010116469ndash72
[5] Moscicki AB Cox JT Practice improvement in cervical screening and management(PICSM) symposium on management of cervical abnormalities in adolescents andyoung women J Low Genit Tract Dis 20101473ndash80
[6] Sasieni P Castanon A Cuzick J Effectiveness of cervical screening with age popula-tion based casendashcontrol study of prospectively recorded data BMJ 2009339b2968[Erratum in BMJ 2009 339b3115]
[7] Moscicki AB Ma Y Wibbelsman C et al Rate of and risks for regression of cervicalintraepithelial neoplasia 2 in adolescents and young women Obstet Gynecol
20101161373ndash
80
Table 4
Time trends in percent of abnormal index cytology followed by a LEEP within 1 yeara
a Histologyresult is themost severe diagnosis from anycervicalbiopsyor ECCdone after theindex cytologyand beforethe LEEP Cytology result is themost severe diagnosis from the
indexcytologyand any follow-up cytology donebefore LEEPAbbreviations are as detailed for Table 3 CIN3+ includes CIN3 CIN2ndash3 CIS AIS andcancerCIN2 includes CIN2 andCIN1ndash2
bHSIL cytology includes ASC-US ASC-US+ LSIL ASC-H and AGC
7W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx
Please cite this article asKinneyW et alCervical excisional treatment of young womenA population-based study Gynecol Oncol (2014)http dxdoiorg101016jygyno201312037
8132019 Cervical Excizional Treatement of Young Women
[8] Wright Jr TC Massad LS Dunton CJ Spitzer M Wilkinson EJ Solomon D 2006ASCCP-Sponsored Consensus Conference 2006 consensus guidelines for the man-agement of women with abnormal cervical screening tests J Low Genit Tract Dis200711201ndash22 [Erratum in J Low Genit Tract Dis 2008 12 255]
[9] Kyrgiou M Koliopoulos G Martin-Hirsch P Arbyn M Prendiville WParaskevaidis E Obstetric outcomes after conservative treatment forintraepithelial or early invasive cervical lesions systematic review and meta-analysis Lancet 2006367489ndash98
[10] Sadler L Saftlas A Wang W Exeter M Whittaker J McCowan L Treatmentfor cervical intraepithelial neoplasia and risk of preterm delivery JAMA20042912100ndash6
[11] Samson SL Bentley JR Fahey TJ McKay DJ Gill GH The effect of loop electro-surgical excision procedure on future pregnancy outcome Obstet Gynecol2005105325ndash32
[12] Yabroff KRSaraiya M Meissner HI HaggstromDA Wideroff L Yuan G et al Special-ty differences in primary care physician reports of Papanicolaou test screeningpractices a national survey 2006 to 2007 Ann Intern Med 2009151602ndash11
[13] Lee JW Berkowitz Z Saraiya M Low-risk human papillomavirus testing and othernonrecommended human papillomavirus testing practices among US health careproviders Obstet Gynecol 20111184ndash13
[14] Roland KB Soman A Benard VB Saraiya M Human papillomavirus and Papanicolaoutests screening interval recommendations in the United States Am J Obstet Gynecol2011205447e1ndash8
[15] Saraiya M Berkowitz Z Yabroff KR Wideroff L Kobrin S Benard V Cervical cancerscreening with both human papillomavirus and Papanicolaou testing vsPapanicolaou testing alone what screeningintervals are physicians recommendingArch Intern Med 2010170977ndash85
[16] Wheeler CM Hunt WC Cuzick J et al A population-based study of human papillo-mavirus genotype prevalence in the United States baseline measures prior tomass human papillomavirus vaccination Int J Cancer Jan 1 2013132(1)198ndash207
[17] CastlePE SchiffmanM Wheeler CMSolomon D Evidence forfrequent regression of cervical intraepithelial neoplasia-grade 2 Obstet Gynecol 200911318ndash25
[18] Robertson AJ Anderson JM Beck JS et al Observer variability in histopathologicalreporting of cervical biopsy specimens J Clin Pathol 198942231ndash8
[19] Wright Jr TC MassadLS DuntonCJ SpitzerM Wilkinson EJSolomonD 2006AmericanSociety for Colposcopy and Cervical Pathology-sponsored Consensus Conference 2006consensus guidelines for the management of women with cervical intraepithelialneoplasia or adenocarcinoma in situ J Low Genit Tract Dis 200711223ndash39
[20] Pretorius RG Zhang WH Belinson JL et al Colposcopically directed biopsy randomcervical biopsy and endocervical curettage in the diagnosis of cervical intraepithelialneoplasia II or worse Am J Obstet Gynecol 2004191430ndash4
[21] Stoler MH Vichnin MD Ferenczy A et al FUTURE I II and III Investigators Theaccuracy of colposcopic biopsy analyses from the placebo arm of the Gardasilclinical trials Int J Cancer 20111281354ndash62
[22] Cox JT More questions about the accuracy of colposcopy what does this mean forcervical cancer prevention Obstet Gynecol 20081111266ndash7
[23] Pretorius RG Belinson JL Burchette RJ Hu S Zhang X Qiao YL Regardless of skillperforming more biopsies increases the sensitivity of colposcopy J Low GenitTract Dis 201115180ndash8
[24] Darragh TM Colgan TJ Cox JT et al LAST Project Work Groups The LowerAnogenital Squamous Terminology Standardization Project for HPV-Associated Le-sions background and consensus recommendations from the College of AmericanPathologists and the American Society for Colposcopy and Cervical Pathology JLow Genit Tract Dis 201216205ndash42
8 W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx
Pleasecite this article as KinneyW et al Cervical excisional treatment of young womenA population-based study Gynecol Oncol (2014) http dxdoiorg101016jygyno201312037
8132019 Cervical Excizional Treatement of Young Women
a p-Values are for test of trend in rates over the 1047297ve year period
3W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx
Please cite this article asKinneyW et alCervical excisional treatment of young womenA population-based study Gynecol Oncol (2014)http dxdoiorg101016jygyno201312037
8132019 Cervical Excizional Treatement of Young Women
a Follow-up classi1047297cation is hierarchical colposcopy with cervical biopsyor endocervical curettage (ECC)else othergynecologic procedure else follow-up cytology else no follow-up
Colposcopywithout biopsyor curettage is notascertainedby theNew MexicoHPV PapRegistry(NMHPVPR) Womenwith LEEP andno precedingcolposcopy areincluded in thecolpos-
copy category Other gynecologic procedures include endometrial vaginal and vulvar biopsies and hysterectomies Follow-up cytology is de1047297ned as cervical cytology within 300 days of
the index cytology Cytologic results are as follows atypical squamous cells of unknown signi1047297cance (ASC-US) is negative for high-risk human papillomavirus (HPV) or HPV status un-knownASC-US+ is positive forhigh-risk HPVde1047297nedas positive forone or more HPVtypes including16 18 3133 35 3945 51 52 56 5859 and68 low-gradeintraepitheliallesion
(LSIL) atypical squamous cells-cannot rule out high-grade (ASC-H) atypical glandular cells (AGC) and high-grade intraepithelial lesion (HSIL)
Fig 1 Percent of women with colposcopic biopsy or endocervical curettage (ECC) within
12 months of abnormal index screeningcytology by ageof woman andresultof cytology
Cytology results are classi1047297ed as ASC-US [atypical squamous cells of undetermined
signi1047297cance negative for high-risk humanpapillomavirus (HPV)or HPV statusunknown]
ASC-US+ [ASC-US positive for high-risk HPV] LSIL [low-grade squamous intraepithelial
lesion] ASC-H[atypical squamous cells-cannot rule out high-grade] and HSIL [high-grade
squamous intraepithelial lesion]
4 W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx
Pleasecite this article as KinneyW et al Cervical excisional treatment of young womenA population-based study Gynecol Oncol (2014) http dxdoiorg101016jygyno201312037
8132019 Cervical Excizional Treatement of Young Women
AlthoughLEEPSperformed within1 year of theindexcytologyaccounted forthe majority (70) some women received LEEP treatment more than 1 year after theindexcytology In the
secondyear followingthe index cytologythe percent of womenreceiving LEEP increased from 352 at 12 monthsto 39at 24 monthsfor HSIL cytologyfrom 179 to 211 forASC-H
from 53 to 67 for ASC-US+ [high-risk HPV positive] and LSIL combined from 96 to 112 for AGC and from 05 to 11 for ASC-US [high-risk HPV negative or unknown]a Histology resultis themost severediagnosis from anycervicalbiopsyor ECCdone after theindex cytology andbefore theLEEP Cytology result is themost severediagnosis from the
index cytology and any follow-upcytology done before LEEP Cervical intraepithelial neoplasia grade3 (CIN3+) includes CIN3 CIN grades 2ndash3 (CIN2ndash3) carcinoma in situ (CIS) adeno-
carcinoma in situ (AIS) and cancer cervical intraepithelial neoplasia grade 2 (CIN2) includes CIN2 and CIN grades 1ndash2 (CIN1ndash2) abbreviations for cytologic results are as outlined in
Table 2 less than high-grade squamous intraepithelial lesions (bHSIL) cytology includes ASC-US ASC-US+ LSIL ASC-H and AGC
6 W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx
Pleasecite this article as KinneyW et al Cervical excisional treatment of young womenA population-based study Gynecol Oncol (2014) http dxdoiorg101016jygyno201312037
8132019 Cervical Excizional Treatement of Young Women
implemented (ie CIN2 and CIN3 are grouped as ldquohigh-graderdquo with the
speci1047297cation of CIN grade being optional) then reduction of the potential
harms associated with screening women in their childbearing years can
only be realized by decreasing screening itself rather than encouraging
more appropriate responses to the lesser histologic abnormalities that
precede the majority of LEEPs in the youngest women
Con1047298icts of interest statement
The authors report no con1047298icts of interest
Acknowledgments
Evaluations reported in this publication were funded by the US
National Institute of Allergy and Infectious Diseases (NIAID) and the
US National Cancer Institute (NCI) under cooperative agreements
U19AI084081 and U54CA164336 to CMW The NIAID and NCI had no
role in the study design in the collection analysis and interpretation
of data in the writing of the report and in the decision to submit
the paper for publication The content is solely the responsibility of
the authors and does not necessarily represent the of 1047297cial views of
the US National Institutes of Health The authors had full access to the
data and had 1047297nal responsibility for the decision to submit for publica-
tion The authors (WC WCH HD MR JC and CMW) had access to thedata reviewed provided input and approved the 1047297nal manuscript
submitted for publication Walter Kinney MD and Cosette Wheeler
PhD created the concept of the manuscript Walter Kinney MD and
Helen Dinkelspiel MD wrote the manuscript that was reviewed
and modi1047297ed by all authors William C Hunt performed the data extrac-
tion and analyses Members of the New Mexico HPV Pap Registry
(NMHPVPR) Steering Committee gave input to the manuscript concepts
and supported the directions of the NMHPVPR including the evaluations
presented in this manuscript The NMHPVPR Steering members partici-
pating are as follows Nancy E Joste MD University of New Mexico
Health SciencesCenter and Tricore Reference Laboratories Albuquerque
New Mexico Walter Kinney MD Kaiser Permanente Northern
California Cosette M Wheeler PhD University of New Mexico Health
Sciences Center William C Hunt MS University of New Mexico Health
Sciences Center Deborah Thompson MD MSPH New Mexico Depart-
ment of Health Susan Baum MD MPH New Mexico Department of
Health Linda Gorgos MD MSc former Medical Director of the Infectious
Disease Bureau New Mexico Department of Health Alan Waxman MD
MPH University of New Mexico Health Sciences Center David Espey
MD US Centers for Disease Control and Prevention Jane McGrath MD
University of New Mexico Health Sciences Center Steven Jenison MD
Community Member Mark Schiffman MD MPH US National Cancer
Institute Philip Castle PhD MPH Albert Einstein College of MedicineVicki Benard PhDUS Centers for Disease Control and Prevention Debbie
Saslow PhD American Cancer Society Jane J Kim PhD Harvard School
of Public Health Mark H Stoler MD University of Virginia Jack Cuzick
PhD Wolfson Institute of Preventive Medicine London Giovanna Rossi
Pressley MSc Collective Action Strategies and RWJF Center for Health
Policy at University of New Mexico and Kevin English RPh MPH
Albuquerque Area Southwest Tribal Epidemiology Center (AASTEC) No
compensation was received for contributions to this manuscript by any
named authors or by the NMHPVPR Steering Committee members
References
[1] Saslow D Soloman D Lawson HW Killackey M Kulasingam SL Cain J et alAmerican Cancer Society American Society for Colposcopy and Cervical Pathologyand American Society for Clinical Pathology screening guidelines for the preventionand early detection of cervical cancer CA Cancer J Clin 201262147ndash72
[2] Moyer VA USPreventive ServicesTaskForce Screeningfor cervical cancer USpreven-tive services taskforce recommendation statement Ann InternMed 2012156880ndash91
[3] ACOG Committee on Practice BulletinsmdashGynecology ACOG Practice Bulletin no 109cervical cytology screening Obstet Gynecol 20091141409ndash20
[4] American College of Obstetricians and Gynecologists ACOG Committee Opinion No463 cervical cancer in adolescents screening evaluation and management ObstetGynecol 2010116469ndash72
[5] Moscicki AB Cox JT Practice improvement in cervical screening and management(PICSM) symposium on management of cervical abnormalities in adolescents andyoung women J Low Genit Tract Dis 20101473ndash80
[6] Sasieni P Castanon A Cuzick J Effectiveness of cervical screening with age popula-tion based casendashcontrol study of prospectively recorded data BMJ 2009339b2968[Erratum in BMJ 2009 339b3115]
[7] Moscicki AB Ma Y Wibbelsman C et al Rate of and risks for regression of cervicalintraepithelial neoplasia 2 in adolescents and young women Obstet Gynecol
20101161373ndash
80
Table 4
Time trends in percent of abnormal index cytology followed by a LEEP within 1 yeara
a Histologyresult is themost severe diagnosis from anycervicalbiopsyor ECCdone after theindex cytologyand beforethe LEEP Cytology result is themost severe diagnosis from the
indexcytologyand any follow-up cytology donebefore LEEPAbbreviations are as detailed for Table 3 CIN3+ includes CIN3 CIN2ndash3 CIS AIS andcancerCIN2 includes CIN2 andCIN1ndash2
bHSIL cytology includes ASC-US ASC-US+ LSIL ASC-H and AGC
7W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx
Please cite this article asKinneyW et alCervical excisional treatment of young womenA population-based study Gynecol Oncol (2014)http dxdoiorg101016jygyno201312037
8132019 Cervical Excizional Treatement of Young Women
[8] Wright Jr TC Massad LS Dunton CJ Spitzer M Wilkinson EJ Solomon D 2006ASCCP-Sponsored Consensus Conference 2006 consensus guidelines for the man-agement of women with abnormal cervical screening tests J Low Genit Tract Dis200711201ndash22 [Erratum in J Low Genit Tract Dis 2008 12 255]
[9] Kyrgiou M Koliopoulos G Martin-Hirsch P Arbyn M Prendiville WParaskevaidis E Obstetric outcomes after conservative treatment forintraepithelial or early invasive cervical lesions systematic review and meta-analysis Lancet 2006367489ndash98
[10] Sadler L Saftlas A Wang W Exeter M Whittaker J McCowan L Treatmentfor cervical intraepithelial neoplasia and risk of preterm delivery JAMA20042912100ndash6
[11] Samson SL Bentley JR Fahey TJ McKay DJ Gill GH The effect of loop electro-surgical excision procedure on future pregnancy outcome Obstet Gynecol2005105325ndash32
[12] Yabroff KRSaraiya M Meissner HI HaggstromDA Wideroff L Yuan G et al Special-ty differences in primary care physician reports of Papanicolaou test screeningpractices a national survey 2006 to 2007 Ann Intern Med 2009151602ndash11
[13] Lee JW Berkowitz Z Saraiya M Low-risk human papillomavirus testing and othernonrecommended human papillomavirus testing practices among US health careproviders Obstet Gynecol 20111184ndash13
[14] Roland KB Soman A Benard VB Saraiya M Human papillomavirus and Papanicolaoutests screening interval recommendations in the United States Am J Obstet Gynecol2011205447e1ndash8
[15] Saraiya M Berkowitz Z Yabroff KR Wideroff L Kobrin S Benard V Cervical cancerscreening with both human papillomavirus and Papanicolaou testing vsPapanicolaou testing alone what screeningintervals are physicians recommendingArch Intern Med 2010170977ndash85
[16] Wheeler CM Hunt WC Cuzick J et al A population-based study of human papillo-mavirus genotype prevalence in the United States baseline measures prior tomass human papillomavirus vaccination Int J Cancer Jan 1 2013132(1)198ndash207
[17] CastlePE SchiffmanM Wheeler CMSolomon D Evidence forfrequent regression of cervical intraepithelial neoplasia-grade 2 Obstet Gynecol 200911318ndash25
[18] Robertson AJ Anderson JM Beck JS et al Observer variability in histopathologicalreporting of cervical biopsy specimens J Clin Pathol 198942231ndash8
[19] Wright Jr TC MassadLS DuntonCJ SpitzerM Wilkinson EJSolomonD 2006AmericanSociety for Colposcopy and Cervical Pathology-sponsored Consensus Conference 2006consensus guidelines for the management of women with cervical intraepithelialneoplasia or adenocarcinoma in situ J Low Genit Tract Dis 200711223ndash39
[20] Pretorius RG Zhang WH Belinson JL et al Colposcopically directed biopsy randomcervical biopsy and endocervical curettage in the diagnosis of cervical intraepithelialneoplasia II or worse Am J Obstet Gynecol 2004191430ndash4
[21] Stoler MH Vichnin MD Ferenczy A et al FUTURE I II and III Investigators Theaccuracy of colposcopic biopsy analyses from the placebo arm of the Gardasilclinical trials Int J Cancer 20111281354ndash62
[22] Cox JT More questions about the accuracy of colposcopy what does this mean forcervical cancer prevention Obstet Gynecol 20081111266ndash7
[23] Pretorius RG Belinson JL Burchette RJ Hu S Zhang X Qiao YL Regardless of skillperforming more biopsies increases the sensitivity of colposcopy J Low GenitTract Dis 201115180ndash8
[24] Darragh TM Colgan TJ Cox JT et al LAST Project Work Groups The LowerAnogenital Squamous Terminology Standardization Project for HPV-Associated Le-sions background and consensus recommendations from the College of AmericanPathologists and the American Society for Colposcopy and Cervical Pathology JLow Genit Tract Dis 201216205ndash42
8 W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx
Pleasecite this article as KinneyW et al Cervical excisional treatment of young womenA population-based study Gynecol Oncol (2014) http dxdoiorg101016jygyno201312037
8132019 Cervical Excizional Treatement of Young Women
a Follow-up classi1047297cation is hierarchical colposcopy with cervical biopsyor endocervical curettage (ECC)else othergynecologic procedure else follow-up cytology else no follow-up
Colposcopywithout biopsyor curettage is notascertainedby theNew MexicoHPV PapRegistry(NMHPVPR) Womenwith LEEP andno precedingcolposcopy areincluded in thecolpos-
copy category Other gynecologic procedures include endometrial vaginal and vulvar biopsies and hysterectomies Follow-up cytology is de1047297ned as cervical cytology within 300 days of
the index cytology Cytologic results are as follows atypical squamous cells of unknown signi1047297cance (ASC-US) is negative for high-risk human papillomavirus (HPV) or HPV status un-knownASC-US+ is positive forhigh-risk HPVde1047297nedas positive forone or more HPVtypes including16 18 3133 35 3945 51 52 56 5859 and68 low-gradeintraepitheliallesion
(LSIL) atypical squamous cells-cannot rule out high-grade (ASC-H) atypical glandular cells (AGC) and high-grade intraepithelial lesion (HSIL)
Fig 1 Percent of women with colposcopic biopsy or endocervical curettage (ECC) within
12 months of abnormal index screeningcytology by ageof woman andresultof cytology
Cytology results are classi1047297ed as ASC-US [atypical squamous cells of undetermined
signi1047297cance negative for high-risk humanpapillomavirus (HPV)or HPV statusunknown]
ASC-US+ [ASC-US positive for high-risk HPV] LSIL [low-grade squamous intraepithelial
lesion] ASC-H[atypical squamous cells-cannot rule out high-grade] and HSIL [high-grade
squamous intraepithelial lesion]
4 W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx
Pleasecite this article as KinneyW et al Cervical excisional treatment of young womenA population-based study Gynecol Oncol (2014) http dxdoiorg101016jygyno201312037
8132019 Cervical Excizional Treatement of Young Women
AlthoughLEEPSperformed within1 year of theindexcytologyaccounted forthe majority (70) some women received LEEP treatment more than 1 year after theindexcytology In the
secondyear followingthe index cytologythe percent of womenreceiving LEEP increased from 352 at 12 monthsto 39at 24 monthsfor HSIL cytologyfrom 179 to 211 forASC-H
from 53 to 67 for ASC-US+ [high-risk HPV positive] and LSIL combined from 96 to 112 for AGC and from 05 to 11 for ASC-US [high-risk HPV negative or unknown]a Histology resultis themost severediagnosis from anycervicalbiopsyor ECCdone after theindex cytology andbefore theLEEP Cytology result is themost severediagnosis from the
index cytology and any follow-upcytology done before LEEP Cervical intraepithelial neoplasia grade3 (CIN3+) includes CIN3 CIN grades 2ndash3 (CIN2ndash3) carcinoma in situ (CIS) adeno-
carcinoma in situ (AIS) and cancer cervical intraepithelial neoplasia grade 2 (CIN2) includes CIN2 and CIN grades 1ndash2 (CIN1ndash2) abbreviations for cytologic results are as outlined in
Table 2 less than high-grade squamous intraepithelial lesions (bHSIL) cytology includes ASC-US ASC-US+ LSIL ASC-H and AGC
6 W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx
Pleasecite this article as KinneyW et al Cervical excisional treatment of young womenA population-based study Gynecol Oncol (2014) http dxdoiorg101016jygyno201312037
8132019 Cervical Excizional Treatement of Young Women
implemented (ie CIN2 and CIN3 are grouped as ldquohigh-graderdquo with the
speci1047297cation of CIN grade being optional) then reduction of the potential
harms associated with screening women in their childbearing years can
only be realized by decreasing screening itself rather than encouraging
more appropriate responses to the lesser histologic abnormalities that
precede the majority of LEEPs in the youngest women
Con1047298icts of interest statement
The authors report no con1047298icts of interest
Acknowledgments
Evaluations reported in this publication were funded by the US
National Institute of Allergy and Infectious Diseases (NIAID) and the
US National Cancer Institute (NCI) under cooperative agreements
U19AI084081 and U54CA164336 to CMW The NIAID and NCI had no
role in the study design in the collection analysis and interpretation
of data in the writing of the report and in the decision to submit
the paper for publication The content is solely the responsibility of
the authors and does not necessarily represent the of 1047297cial views of
the US National Institutes of Health The authors had full access to the
data and had 1047297nal responsibility for the decision to submit for publica-
tion The authors (WC WCH HD MR JC and CMW) had access to thedata reviewed provided input and approved the 1047297nal manuscript
submitted for publication Walter Kinney MD and Cosette Wheeler
PhD created the concept of the manuscript Walter Kinney MD and
Helen Dinkelspiel MD wrote the manuscript that was reviewed
and modi1047297ed by all authors William C Hunt performed the data extrac-
tion and analyses Members of the New Mexico HPV Pap Registry
(NMHPVPR) Steering Committee gave input to the manuscript concepts
and supported the directions of the NMHPVPR including the evaluations
presented in this manuscript The NMHPVPR Steering members partici-
pating are as follows Nancy E Joste MD University of New Mexico
Health SciencesCenter and Tricore Reference Laboratories Albuquerque
New Mexico Walter Kinney MD Kaiser Permanente Northern
California Cosette M Wheeler PhD University of New Mexico Health
Sciences Center William C Hunt MS University of New Mexico Health
Sciences Center Deborah Thompson MD MSPH New Mexico Depart-
ment of Health Susan Baum MD MPH New Mexico Department of
Health Linda Gorgos MD MSc former Medical Director of the Infectious
Disease Bureau New Mexico Department of Health Alan Waxman MD
MPH University of New Mexico Health Sciences Center David Espey
MD US Centers for Disease Control and Prevention Jane McGrath MD
University of New Mexico Health Sciences Center Steven Jenison MD
Community Member Mark Schiffman MD MPH US National Cancer
Institute Philip Castle PhD MPH Albert Einstein College of MedicineVicki Benard PhDUS Centers for Disease Control and Prevention Debbie
Saslow PhD American Cancer Society Jane J Kim PhD Harvard School
of Public Health Mark H Stoler MD University of Virginia Jack Cuzick
PhD Wolfson Institute of Preventive Medicine London Giovanna Rossi
Pressley MSc Collective Action Strategies and RWJF Center for Health
Policy at University of New Mexico and Kevin English RPh MPH
Albuquerque Area Southwest Tribal Epidemiology Center (AASTEC) No
compensation was received for contributions to this manuscript by any
named authors or by the NMHPVPR Steering Committee members
References
[1] Saslow D Soloman D Lawson HW Killackey M Kulasingam SL Cain J et alAmerican Cancer Society American Society for Colposcopy and Cervical Pathologyand American Society for Clinical Pathology screening guidelines for the preventionand early detection of cervical cancer CA Cancer J Clin 201262147ndash72
[2] Moyer VA USPreventive ServicesTaskForce Screeningfor cervical cancer USpreven-tive services taskforce recommendation statement Ann InternMed 2012156880ndash91
[3] ACOG Committee on Practice BulletinsmdashGynecology ACOG Practice Bulletin no 109cervical cytology screening Obstet Gynecol 20091141409ndash20
[4] American College of Obstetricians and Gynecologists ACOG Committee Opinion No463 cervical cancer in adolescents screening evaluation and management ObstetGynecol 2010116469ndash72
[5] Moscicki AB Cox JT Practice improvement in cervical screening and management(PICSM) symposium on management of cervical abnormalities in adolescents andyoung women J Low Genit Tract Dis 20101473ndash80
[6] Sasieni P Castanon A Cuzick J Effectiveness of cervical screening with age popula-tion based casendashcontrol study of prospectively recorded data BMJ 2009339b2968[Erratum in BMJ 2009 339b3115]
[7] Moscicki AB Ma Y Wibbelsman C et al Rate of and risks for regression of cervicalintraepithelial neoplasia 2 in adolescents and young women Obstet Gynecol
20101161373ndash
80
Table 4
Time trends in percent of abnormal index cytology followed by a LEEP within 1 yeara
a Histologyresult is themost severe diagnosis from anycervicalbiopsyor ECCdone after theindex cytologyand beforethe LEEP Cytology result is themost severe diagnosis from the
indexcytologyand any follow-up cytology donebefore LEEPAbbreviations are as detailed for Table 3 CIN3+ includes CIN3 CIN2ndash3 CIS AIS andcancerCIN2 includes CIN2 andCIN1ndash2
bHSIL cytology includes ASC-US ASC-US+ LSIL ASC-H and AGC
7W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx
Please cite this article asKinneyW et alCervical excisional treatment of young womenA population-based study Gynecol Oncol (2014)http dxdoiorg101016jygyno201312037
8132019 Cervical Excizional Treatement of Young Women
[8] Wright Jr TC Massad LS Dunton CJ Spitzer M Wilkinson EJ Solomon D 2006ASCCP-Sponsored Consensus Conference 2006 consensus guidelines for the man-agement of women with abnormal cervical screening tests J Low Genit Tract Dis200711201ndash22 [Erratum in J Low Genit Tract Dis 2008 12 255]
[9] Kyrgiou M Koliopoulos G Martin-Hirsch P Arbyn M Prendiville WParaskevaidis E Obstetric outcomes after conservative treatment forintraepithelial or early invasive cervical lesions systematic review and meta-analysis Lancet 2006367489ndash98
[10] Sadler L Saftlas A Wang W Exeter M Whittaker J McCowan L Treatmentfor cervical intraepithelial neoplasia and risk of preterm delivery JAMA20042912100ndash6
[11] Samson SL Bentley JR Fahey TJ McKay DJ Gill GH The effect of loop electro-surgical excision procedure on future pregnancy outcome Obstet Gynecol2005105325ndash32
[12] Yabroff KRSaraiya M Meissner HI HaggstromDA Wideroff L Yuan G et al Special-ty differences in primary care physician reports of Papanicolaou test screeningpractices a national survey 2006 to 2007 Ann Intern Med 2009151602ndash11
[13] Lee JW Berkowitz Z Saraiya M Low-risk human papillomavirus testing and othernonrecommended human papillomavirus testing practices among US health careproviders Obstet Gynecol 20111184ndash13
[14] Roland KB Soman A Benard VB Saraiya M Human papillomavirus and Papanicolaoutests screening interval recommendations in the United States Am J Obstet Gynecol2011205447e1ndash8
[15] Saraiya M Berkowitz Z Yabroff KR Wideroff L Kobrin S Benard V Cervical cancerscreening with both human papillomavirus and Papanicolaou testing vsPapanicolaou testing alone what screeningintervals are physicians recommendingArch Intern Med 2010170977ndash85
[16] Wheeler CM Hunt WC Cuzick J et al A population-based study of human papillo-mavirus genotype prevalence in the United States baseline measures prior tomass human papillomavirus vaccination Int J Cancer Jan 1 2013132(1)198ndash207
[17] CastlePE SchiffmanM Wheeler CMSolomon D Evidence forfrequent regression of cervical intraepithelial neoplasia-grade 2 Obstet Gynecol 200911318ndash25
[18] Robertson AJ Anderson JM Beck JS et al Observer variability in histopathologicalreporting of cervical biopsy specimens J Clin Pathol 198942231ndash8
[19] Wright Jr TC MassadLS DuntonCJ SpitzerM Wilkinson EJSolomonD 2006AmericanSociety for Colposcopy and Cervical Pathology-sponsored Consensus Conference 2006consensus guidelines for the management of women with cervical intraepithelialneoplasia or adenocarcinoma in situ J Low Genit Tract Dis 200711223ndash39
[20] Pretorius RG Zhang WH Belinson JL et al Colposcopically directed biopsy randomcervical biopsy and endocervical curettage in the diagnosis of cervical intraepithelialneoplasia II or worse Am J Obstet Gynecol 2004191430ndash4
[21] Stoler MH Vichnin MD Ferenczy A et al FUTURE I II and III Investigators Theaccuracy of colposcopic biopsy analyses from the placebo arm of the Gardasilclinical trials Int J Cancer 20111281354ndash62
[22] Cox JT More questions about the accuracy of colposcopy what does this mean forcervical cancer prevention Obstet Gynecol 20081111266ndash7
[23] Pretorius RG Belinson JL Burchette RJ Hu S Zhang X Qiao YL Regardless of skillperforming more biopsies increases the sensitivity of colposcopy J Low GenitTract Dis 201115180ndash8
[24] Darragh TM Colgan TJ Cox JT et al LAST Project Work Groups The LowerAnogenital Squamous Terminology Standardization Project for HPV-Associated Le-sions background and consensus recommendations from the College of AmericanPathologists and the American Society for Colposcopy and Cervical Pathology JLow Genit Tract Dis 201216205ndash42
8 W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx
Pleasecite this article as KinneyW et al Cervical excisional treatment of young womenA population-based study Gynecol Oncol (2014) http dxdoiorg101016jygyno201312037
8132019 Cervical Excizional Treatement of Young Women
AlthoughLEEPSperformed within1 year of theindexcytologyaccounted forthe majority (70) some women received LEEP treatment more than 1 year after theindexcytology In the
secondyear followingthe index cytologythe percent of womenreceiving LEEP increased from 352 at 12 monthsto 39at 24 monthsfor HSIL cytologyfrom 179 to 211 forASC-H
from 53 to 67 for ASC-US+ [high-risk HPV positive] and LSIL combined from 96 to 112 for AGC and from 05 to 11 for ASC-US [high-risk HPV negative or unknown]a Histology resultis themost severediagnosis from anycervicalbiopsyor ECCdone after theindex cytology andbefore theLEEP Cytology result is themost severediagnosis from the
index cytology and any follow-upcytology done before LEEP Cervical intraepithelial neoplasia grade3 (CIN3+) includes CIN3 CIN grades 2ndash3 (CIN2ndash3) carcinoma in situ (CIS) adeno-
carcinoma in situ (AIS) and cancer cervical intraepithelial neoplasia grade 2 (CIN2) includes CIN2 and CIN grades 1ndash2 (CIN1ndash2) abbreviations for cytologic results are as outlined in
Table 2 less than high-grade squamous intraepithelial lesions (bHSIL) cytology includes ASC-US ASC-US+ LSIL ASC-H and AGC
6 W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx
Pleasecite this article as KinneyW et al Cervical excisional treatment of young womenA population-based study Gynecol Oncol (2014) http dxdoiorg101016jygyno201312037
8132019 Cervical Excizional Treatement of Young Women
implemented (ie CIN2 and CIN3 are grouped as ldquohigh-graderdquo with the
speci1047297cation of CIN grade being optional) then reduction of the potential
harms associated with screening women in their childbearing years can
only be realized by decreasing screening itself rather than encouraging
more appropriate responses to the lesser histologic abnormalities that
precede the majority of LEEPs in the youngest women
Con1047298icts of interest statement
The authors report no con1047298icts of interest
Acknowledgments
Evaluations reported in this publication were funded by the US
National Institute of Allergy and Infectious Diseases (NIAID) and the
US National Cancer Institute (NCI) under cooperative agreements
U19AI084081 and U54CA164336 to CMW The NIAID and NCI had no
role in the study design in the collection analysis and interpretation
of data in the writing of the report and in the decision to submit
the paper for publication The content is solely the responsibility of
the authors and does not necessarily represent the of 1047297cial views of
the US National Institutes of Health The authors had full access to the
data and had 1047297nal responsibility for the decision to submit for publica-
tion The authors (WC WCH HD MR JC and CMW) had access to thedata reviewed provided input and approved the 1047297nal manuscript
submitted for publication Walter Kinney MD and Cosette Wheeler
PhD created the concept of the manuscript Walter Kinney MD and
Helen Dinkelspiel MD wrote the manuscript that was reviewed
and modi1047297ed by all authors William C Hunt performed the data extrac-
tion and analyses Members of the New Mexico HPV Pap Registry
(NMHPVPR) Steering Committee gave input to the manuscript concepts
and supported the directions of the NMHPVPR including the evaluations
presented in this manuscript The NMHPVPR Steering members partici-
pating are as follows Nancy E Joste MD University of New Mexico
Health SciencesCenter and Tricore Reference Laboratories Albuquerque
New Mexico Walter Kinney MD Kaiser Permanente Northern
California Cosette M Wheeler PhD University of New Mexico Health
Sciences Center William C Hunt MS University of New Mexico Health
Sciences Center Deborah Thompson MD MSPH New Mexico Depart-
ment of Health Susan Baum MD MPH New Mexico Department of
Health Linda Gorgos MD MSc former Medical Director of the Infectious
Disease Bureau New Mexico Department of Health Alan Waxman MD
MPH University of New Mexico Health Sciences Center David Espey
MD US Centers for Disease Control and Prevention Jane McGrath MD
University of New Mexico Health Sciences Center Steven Jenison MD
Community Member Mark Schiffman MD MPH US National Cancer
Institute Philip Castle PhD MPH Albert Einstein College of MedicineVicki Benard PhDUS Centers for Disease Control and Prevention Debbie
Saslow PhD American Cancer Society Jane J Kim PhD Harvard School
of Public Health Mark H Stoler MD University of Virginia Jack Cuzick
PhD Wolfson Institute of Preventive Medicine London Giovanna Rossi
Pressley MSc Collective Action Strategies and RWJF Center for Health
Policy at University of New Mexico and Kevin English RPh MPH
Albuquerque Area Southwest Tribal Epidemiology Center (AASTEC) No
compensation was received for contributions to this manuscript by any
named authors or by the NMHPVPR Steering Committee members
References
[1] Saslow D Soloman D Lawson HW Killackey M Kulasingam SL Cain J et alAmerican Cancer Society American Society for Colposcopy and Cervical Pathologyand American Society for Clinical Pathology screening guidelines for the preventionand early detection of cervical cancer CA Cancer J Clin 201262147ndash72
[2] Moyer VA USPreventive ServicesTaskForce Screeningfor cervical cancer USpreven-tive services taskforce recommendation statement Ann InternMed 2012156880ndash91
[3] ACOG Committee on Practice BulletinsmdashGynecology ACOG Practice Bulletin no 109cervical cytology screening Obstet Gynecol 20091141409ndash20
[4] American College of Obstetricians and Gynecologists ACOG Committee Opinion No463 cervical cancer in adolescents screening evaluation and management ObstetGynecol 2010116469ndash72
[5] Moscicki AB Cox JT Practice improvement in cervical screening and management(PICSM) symposium on management of cervical abnormalities in adolescents andyoung women J Low Genit Tract Dis 20101473ndash80
[6] Sasieni P Castanon A Cuzick J Effectiveness of cervical screening with age popula-tion based casendashcontrol study of prospectively recorded data BMJ 2009339b2968[Erratum in BMJ 2009 339b3115]
[7] Moscicki AB Ma Y Wibbelsman C et al Rate of and risks for regression of cervicalintraepithelial neoplasia 2 in adolescents and young women Obstet Gynecol
20101161373ndash
80
Table 4
Time trends in percent of abnormal index cytology followed by a LEEP within 1 yeara
a Histologyresult is themost severe diagnosis from anycervicalbiopsyor ECCdone after theindex cytologyand beforethe LEEP Cytology result is themost severe diagnosis from the
indexcytologyand any follow-up cytology donebefore LEEPAbbreviations are as detailed for Table 3 CIN3+ includes CIN3 CIN2ndash3 CIS AIS andcancerCIN2 includes CIN2 andCIN1ndash2
bHSIL cytology includes ASC-US ASC-US+ LSIL ASC-H and AGC
7W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx
Please cite this article asKinneyW et alCervical excisional treatment of young womenA population-based study Gynecol Oncol (2014)http dxdoiorg101016jygyno201312037
8132019 Cervical Excizional Treatement of Young Women
[8] Wright Jr TC Massad LS Dunton CJ Spitzer M Wilkinson EJ Solomon D 2006ASCCP-Sponsored Consensus Conference 2006 consensus guidelines for the man-agement of women with abnormal cervical screening tests J Low Genit Tract Dis200711201ndash22 [Erratum in J Low Genit Tract Dis 2008 12 255]
[9] Kyrgiou M Koliopoulos G Martin-Hirsch P Arbyn M Prendiville WParaskevaidis E Obstetric outcomes after conservative treatment forintraepithelial or early invasive cervical lesions systematic review and meta-analysis Lancet 2006367489ndash98
[10] Sadler L Saftlas A Wang W Exeter M Whittaker J McCowan L Treatmentfor cervical intraepithelial neoplasia and risk of preterm delivery JAMA20042912100ndash6
[11] Samson SL Bentley JR Fahey TJ McKay DJ Gill GH The effect of loop electro-surgical excision procedure on future pregnancy outcome Obstet Gynecol2005105325ndash32
[12] Yabroff KRSaraiya M Meissner HI HaggstromDA Wideroff L Yuan G et al Special-ty differences in primary care physician reports of Papanicolaou test screeningpractices a national survey 2006 to 2007 Ann Intern Med 2009151602ndash11
[13] Lee JW Berkowitz Z Saraiya M Low-risk human papillomavirus testing and othernonrecommended human papillomavirus testing practices among US health careproviders Obstet Gynecol 20111184ndash13
[14] Roland KB Soman A Benard VB Saraiya M Human papillomavirus and Papanicolaoutests screening interval recommendations in the United States Am J Obstet Gynecol2011205447e1ndash8
[15] Saraiya M Berkowitz Z Yabroff KR Wideroff L Kobrin S Benard V Cervical cancerscreening with both human papillomavirus and Papanicolaou testing vsPapanicolaou testing alone what screeningintervals are physicians recommendingArch Intern Med 2010170977ndash85
[16] Wheeler CM Hunt WC Cuzick J et al A population-based study of human papillo-mavirus genotype prevalence in the United States baseline measures prior tomass human papillomavirus vaccination Int J Cancer Jan 1 2013132(1)198ndash207
[17] CastlePE SchiffmanM Wheeler CMSolomon D Evidence forfrequent regression of cervical intraepithelial neoplasia-grade 2 Obstet Gynecol 200911318ndash25
[18] Robertson AJ Anderson JM Beck JS et al Observer variability in histopathologicalreporting of cervical biopsy specimens J Clin Pathol 198942231ndash8
[19] Wright Jr TC MassadLS DuntonCJ SpitzerM Wilkinson EJSolomonD 2006AmericanSociety for Colposcopy and Cervical Pathology-sponsored Consensus Conference 2006consensus guidelines for the management of women with cervical intraepithelialneoplasia or adenocarcinoma in situ J Low Genit Tract Dis 200711223ndash39
[20] Pretorius RG Zhang WH Belinson JL et al Colposcopically directed biopsy randomcervical biopsy and endocervical curettage in the diagnosis of cervical intraepithelialneoplasia II or worse Am J Obstet Gynecol 2004191430ndash4
[21] Stoler MH Vichnin MD Ferenczy A et al FUTURE I II and III Investigators Theaccuracy of colposcopic biopsy analyses from the placebo arm of the Gardasilclinical trials Int J Cancer 20111281354ndash62
[22] Cox JT More questions about the accuracy of colposcopy what does this mean forcervical cancer prevention Obstet Gynecol 20081111266ndash7
[23] Pretorius RG Belinson JL Burchette RJ Hu S Zhang X Qiao YL Regardless of skillperforming more biopsies increases the sensitivity of colposcopy J Low GenitTract Dis 201115180ndash8
[24] Darragh TM Colgan TJ Cox JT et al LAST Project Work Groups The LowerAnogenital Squamous Terminology Standardization Project for HPV-Associated Le-sions background and consensus recommendations from the College of AmericanPathologists and the American Society for Colposcopy and Cervical Pathology JLow Genit Tract Dis 201216205ndash42
8 W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx
Pleasecite this article as KinneyW et al Cervical excisional treatment of young womenA population-based study Gynecol Oncol (2014) http dxdoiorg101016jygyno201312037
8132019 Cervical Excizional Treatement of Young Women
AlthoughLEEPSperformed within1 year of theindexcytologyaccounted forthe majority (70) some women received LEEP treatment more than 1 year after theindexcytology In the
secondyear followingthe index cytologythe percent of womenreceiving LEEP increased from 352 at 12 monthsto 39at 24 monthsfor HSIL cytologyfrom 179 to 211 forASC-H
from 53 to 67 for ASC-US+ [high-risk HPV positive] and LSIL combined from 96 to 112 for AGC and from 05 to 11 for ASC-US [high-risk HPV negative or unknown]a Histology resultis themost severediagnosis from anycervicalbiopsyor ECCdone after theindex cytology andbefore theLEEP Cytology result is themost severediagnosis from the
index cytology and any follow-upcytology done before LEEP Cervical intraepithelial neoplasia grade3 (CIN3+) includes CIN3 CIN grades 2ndash3 (CIN2ndash3) carcinoma in situ (CIS) adeno-
carcinoma in situ (AIS) and cancer cervical intraepithelial neoplasia grade 2 (CIN2) includes CIN2 and CIN grades 1ndash2 (CIN1ndash2) abbreviations for cytologic results are as outlined in
Table 2 less than high-grade squamous intraepithelial lesions (bHSIL) cytology includes ASC-US ASC-US+ LSIL ASC-H and AGC
6 W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx
Pleasecite this article as KinneyW et al Cervical excisional treatment of young womenA population-based study Gynecol Oncol (2014) http dxdoiorg101016jygyno201312037
8132019 Cervical Excizional Treatement of Young Women
implemented (ie CIN2 and CIN3 are grouped as ldquohigh-graderdquo with the
speci1047297cation of CIN grade being optional) then reduction of the potential
harms associated with screening women in their childbearing years can
only be realized by decreasing screening itself rather than encouraging
more appropriate responses to the lesser histologic abnormalities that
precede the majority of LEEPs in the youngest women
Con1047298icts of interest statement
The authors report no con1047298icts of interest
Acknowledgments
Evaluations reported in this publication were funded by the US
National Institute of Allergy and Infectious Diseases (NIAID) and the
US National Cancer Institute (NCI) under cooperative agreements
U19AI084081 and U54CA164336 to CMW The NIAID and NCI had no
role in the study design in the collection analysis and interpretation
of data in the writing of the report and in the decision to submit
the paper for publication The content is solely the responsibility of
the authors and does not necessarily represent the of 1047297cial views of
the US National Institutes of Health The authors had full access to the
data and had 1047297nal responsibility for the decision to submit for publica-
tion The authors (WC WCH HD MR JC and CMW) had access to thedata reviewed provided input and approved the 1047297nal manuscript
submitted for publication Walter Kinney MD and Cosette Wheeler
PhD created the concept of the manuscript Walter Kinney MD and
Helen Dinkelspiel MD wrote the manuscript that was reviewed
and modi1047297ed by all authors William C Hunt performed the data extrac-
tion and analyses Members of the New Mexico HPV Pap Registry
(NMHPVPR) Steering Committee gave input to the manuscript concepts
and supported the directions of the NMHPVPR including the evaluations
presented in this manuscript The NMHPVPR Steering members partici-
pating are as follows Nancy E Joste MD University of New Mexico
Health SciencesCenter and Tricore Reference Laboratories Albuquerque
New Mexico Walter Kinney MD Kaiser Permanente Northern
California Cosette M Wheeler PhD University of New Mexico Health
Sciences Center William C Hunt MS University of New Mexico Health
Sciences Center Deborah Thompson MD MSPH New Mexico Depart-
ment of Health Susan Baum MD MPH New Mexico Department of
Health Linda Gorgos MD MSc former Medical Director of the Infectious
Disease Bureau New Mexico Department of Health Alan Waxman MD
MPH University of New Mexico Health Sciences Center David Espey
MD US Centers for Disease Control and Prevention Jane McGrath MD
University of New Mexico Health Sciences Center Steven Jenison MD
Community Member Mark Schiffman MD MPH US National Cancer
Institute Philip Castle PhD MPH Albert Einstein College of MedicineVicki Benard PhDUS Centers for Disease Control and Prevention Debbie
Saslow PhD American Cancer Society Jane J Kim PhD Harvard School
of Public Health Mark H Stoler MD University of Virginia Jack Cuzick
PhD Wolfson Institute of Preventive Medicine London Giovanna Rossi
Pressley MSc Collective Action Strategies and RWJF Center for Health
Policy at University of New Mexico and Kevin English RPh MPH
Albuquerque Area Southwest Tribal Epidemiology Center (AASTEC) No
compensation was received for contributions to this manuscript by any
named authors or by the NMHPVPR Steering Committee members
References
[1] Saslow D Soloman D Lawson HW Killackey M Kulasingam SL Cain J et alAmerican Cancer Society American Society for Colposcopy and Cervical Pathologyand American Society for Clinical Pathology screening guidelines for the preventionand early detection of cervical cancer CA Cancer J Clin 201262147ndash72
[2] Moyer VA USPreventive ServicesTaskForce Screeningfor cervical cancer USpreven-tive services taskforce recommendation statement Ann InternMed 2012156880ndash91
[3] ACOG Committee on Practice BulletinsmdashGynecology ACOG Practice Bulletin no 109cervical cytology screening Obstet Gynecol 20091141409ndash20
[4] American College of Obstetricians and Gynecologists ACOG Committee Opinion No463 cervical cancer in adolescents screening evaluation and management ObstetGynecol 2010116469ndash72
[5] Moscicki AB Cox JT Practice improvement in cervical screening and management(PICSM) symposium on management of cervical abnormalities in adolescents andyoung women J Low Genit Tract Dis 20101473ndash80
[6] Sasieni P Castanon A Cuzick J Effectiveness of cervical screening with age popula-tion based casendashcontrol study of prospectively recorded data BMJ 2009339b2968[Erratum in BMJ 2009 339b3115]
[7] Moscicki AB Ma Y Wibbelsman C et al Rate of and risks for regression of cervicalintraepithelial neoplasia 2 in adolescents and young women Obstet Gynecol
20101161373ndash
80
Table 4
Time trends in percent of abnormal index cytology followed by a LEEP within 1 yeara
a Histologyresult is themost severe diagnosis from anycervicalbiopsyor ECCdone after theindex cytologyand beforethe LEEP Cytology result is themost severe diagnosis from the
indexcytologyand any follow-up cytology donebefore LEEPAbbreviations are as detailed for Table 3 CIN3+ includes CIN3 CIN2ndash3 CIS AIS andcancerCIN2 includes CIN2 andCIN1ndash2
bHSIL cytology includes ASC-US ASC-US+ LSIL ASC-H and AGC
7W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx
Please cite this article asKinneyW et alCervical excisional treatment of young womenA population-based study Gynecol Oncol (2014)http dxdoiorg101016jygyno201312037
8132019 Cervical Excizional Treatement of Young Women
[8] Wright Jr TC Massad LS Dunton CJ Spitzer M Wilkinson EJ Solomon D 2006ASCCP-Sponsored Consensus Conference 2006 consensus guidelines for the man-agement of women with abnormal cervical screening tests J Low Genit Tract Dis200711201ndash22 [Erratum in J Low Genit Tract Dis 2008 12 255]
[9] Kyrgiou M Koliopoulos G Martin-Hirsch P Arbyn M Prendiville WParaskevaidis E Obstetric outcomes after conservative treatment forintraepithelial or early invasive cervical lesions systematic review and meta-analysis Lancet 2006367489ndash98
[10] Sadler L Saftlas A Wang W Exeter M Whittaker J McCowan L Treatmentfor cervical intraepithelial neoplasia and risk of preterm delivery JAMA20042912100ndash6
[11] Samson SL Bentley JR Fahey TJ McKay DJ Gill GH The effect of loop electro-surgical excision procedure on future pregnancy outcome Obstet Gynecol2005105325ndash32
[12] Yabroff KRSaraiya M Meissner HI HaggstromDA Wideroff L Yuan G et al Special-ty differences in primary care physician reports of Papanicolaou test screeningpractices a national survey 2006 to 2007 Ann Intern Med 2009151602ndash11
[13] Lee JW Berkowitz Z Saraiya M Low-risk human papillomavirus testing and othernonrecommended human papillomavirus testing practices among US health careproviders Obstet Gynecol 20111184ndash13
[14] Roland KB Soman A Benard VB Saraiya M Human papillomavirus and Papanicolaoutests screening interval recommendations in the United States Am J Obstet Gynecol2011205447e1ndash8
[15] Saraiya M Berkowitz Z Yabroff KR Wideroff L Kobrin S Benard V Cervical cancerscreening with both human papillomavirus and Papanicolaou testing vsPapanicolaou testing alone what screeningintervals are physicians recommendingArch Intern Med 2010170977ndash85
[16] Wheeler CM Hunt WC Cuzick J et al A population-based study of human papillo-mavirus genotype prevalence in the United States baseline measures prior tomass human papillomavirus vaccination Int J Cancer Jan 1 2013132(1)198ndash207
[17] CastlePE SchiffmanM Wheeler CMSolomon D Evidence forfrequent regression of cervical intraepithelial neoplasia-grade 2 Obstet Gynecol 200911318ndash25
[18] Robertson AJ Anderson JM Beck JS et al Observer variability in histopathologicalreporting of cervical biopsy specimens J Clin Pathol 198942231ndash8
[19] Wright Jr TC MassadLS DuntonCJ SpitzerM Wilkinson EJSolomonD 2006AmericanSociety for Colposcopy and Cervical Pathology-sponsored Consensus Conference 2006consensus guidelines for the management of women with cervical intraepithelialneoplasia or adenocarcinoma in situ J Low Genit Tract Dis 200711223ndash39
[20] Pretorius RG Zhang WH Belinson JL et al Colposcopically directed biopsy randomcervical biopsy and endocervical curettage in the diagnosis of cervical intraepithelialneoplasia II or worse Am J Obstet Gynecol 2004191430ndash4
[21] Stoler MH Vichnin MD Ferenczy A et al FUTURE I II and III Investigators Theaccuracy of colposcopic biopsy analyses from the placebo arm of the Gardasilclinical trials Int J Cancer 20111281354ndash62
[22] Cox JT More questions about the accuracy of colposcopy what does this mean forcervical cancer prevention Obstet Gynecol 20081111266ndash7
[23] Pretorius RG Belinson JL Burchette RJ Hu S Zhang X Qiao YL Regardless of skillperforming more biopsies increases the sensitivity of colposcopy J Low GenitTract Dis 201115180ndash8
[24] Darragh TM Colgan TJ Cox JT et al LAST Project Work Groups The LowerAnogenital Squamous Terminology Standardization Project for HPV-Associated Le-sions background and consensus recommendations from the College of AmericanPathologists and the American Society for Colposcopy and Cervical Pathology JLow Genit Tract Dis 201216205ndash42
8 W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx
Pleasecite this article as KinneyW et al Cervical excisional treatment of young womenA population-based study Gynecol Oncol (2014) http dxdoiorg101016jygyno201312037
8132019 Cervical Excizional Treatement of Young Women
implemented (ie CIN2 and CIN3 are grouped as ldquohigh-graderdquo with the
speci1047297cation of CIN grade being optional) then reduction of the potential
harms associated with screening women in their childbearing years can
only be realized by decreasing screening itself rather than encouraging
more appropriate responses to the lesser histologic abnormalities that
precede the majority of LEEPs in the youngest women
Con1047298icts of interest statement
The authors report no con1047298icts of interest
Acknowledgments
Evaluations reported in this publication were funded by the US
National Institute of Allergy and Infectious Diseases (NIAID) and the
US National Cancer Institute (NCI) under cooperative agreements
U19AI084081 and U54CA164336 to CMW The NIAID and NCI had no
role in the study design in the collection analysis and interpretation
of data in the writing of the report and in the decision to submit
the paper for publication The content is solely the responsibility of
the authors and does not necessarily represent the of 1047297cial views of
the US National Institutes of Health The authors had full access to the
data and had 1047297nal responsibility for the decision to submit for publica-
tion The authors (WC WCH HD MR JC and CMW) had access to thedata reviewed provided input and approved the 1047297nal manuscript
submitted for publication Walter Kinney MD and Cosette Wheeler
PhD created the concept of the manuscript Walter Kinney MD and
Helen Dinkelspiel MD wrote the manuscript that was reviewed
and modi1047297ed by all authors William C Hunt performed the data extrac-
tion and analyses Members of the New Mexico HPV Pap Registry
(NMHPVPR) Steering Committee gave input to the manuscript concepts
and supported the directions of the NMHPVPR including the evaluations
presented in this manuscript The NMHPVPR Steering members partici-
pating are as follows Nancy E Joste MD University of New Mexico
Health SciencesCenter and Tricore Reference Laboratories Albuquerque
New Mexico Walter Kinney MD Kaiser Permanente Northern
California Cosette M Wheeler PhD University of New Mexico Health
Sciences Center William C Hunt MS University of New Mexico Health
Sciences Center Deborah Thompson MD MSPH New Mexico Depart-
ment of Health Susan Baum MD MPH New Mexico Department of
Health Linda Gorgos MD MSc former Medical Director of the Infectious
Disease Bureau New Mexico Department of Health Alan Waxman MD
MPH University of New Mexico Health Sciences Center David Espey
MD US Centers for Disease Control and Prevention Jane McGrath MD
University of New Mexico Health Sciences Center Steven Jenison MD
Community Member Mark Schiffman MD MPH US National Cancer
Institute Philip Castle PhD MPH Albert Einstein College of MedicineVicki Benard PhDUS Centers for Disease Control and Prevention Debbie
Saslow PhD American Cancer Society Jane J Kim PhD Harvard School
of Public Health Mark H Stoler MD University of Virginia Jack Cuzick
PhD Wolfson Institute of Preventive Medicine London Giovanna Rossi
Pressley MSc Collective Action Strategies and RWJF Center for Health
Policy at University of New Mexico and Kevin English RPh MPH
Albuquerque Area Southwest Tribal Epidemiology Center (AASTEC) No
compensation was received for contributions to this manuscript by any
named authors or by the NMHPVPR Steering Committee members
References
[1] Saslow D Soloman D Lawson HW Killackey M Kulasingam SL Cain J et alAmerican Cancer Society American Society for Colposcopy and Cervical Pathologyand American Society for Clinical Pathology screening guidelines for the preventionand early detection of cervical cancer CA Cancer J Clin 201262147ndash72
[2] Moyer VA USPreventive ServicesTaskForce Screeningfor cervical cancer USpreven-tive services taskforce recommendation statement Ann InternMed 2012156880ndash91
[3] ACOG Committee on Practice BulletinsmdashGynecology ACOG Practice Bulletin no 109cervical cytology screening Obstet Gynecol 20091141409ndash20
[4] American College of Obstetricians and Gynecologists ACOG Committee Opinion No463 cervical cancer in adolescents screening evaluation and management ObstetGynecol 2010116469ndash72
[5] Moscicki AB Cox JT Practice improvement in cervical screening and management(PICSM) symposium on management of cervical abnormalities in adolescents andyoung women J Low Genit Tract Dis 20101473ndash80
[6] Sasieni P Castanon A Cuzick J Effectiveness of cervical screening with age popula-tion based casendashcontrol study of prospectively recorded data BMJ 2009339b2968[Erratum in BMJ 2009 339b3115]
[7] Moscicki AB Ma Y Wibbelsman C et al Rate of and risks for regression of cervicalintraepithelial neoplasia 2 in adolescents and young women Obstet Gynecol
20101161373ndash
80
Table 4
Time trends in percent of abnormal index cytology followed by a LEEP within 1 yeara
a Histologyresult is themost severe diagnosis from anycervicalbiopsyor ECCdone after theindex cytologyand beforethe LEEP Cytology result is themost severe diagnosis from the
indexcytologyand any follow-up cytology donebefore LEEPAbbreviations are as detailed for Table 3 CIN3+ includes CIN3 CIN2ndash3 CIS AIS andcancerCIN2 includes CIN2 andCIN1ndash2
bHSIL cytology includes ASC-US ASC-US+ LSIL ASC-H and AGC
7W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx
Please cite this article asKinneyW et alCervical excisional treatment of young womenA population-based study Gynecol Oncol (2014)http dxdoiorg101016jygyno201312037
8132019 Cervical Excizional Treatement of Young Women
[8] Wright Jr TC Massad LS Dunton CJ Spitzer M Wilkinson EJ Solomon D 2006ASCCP-Sponsored Consensus Conference 2006 consensus guidelines for the man-agement of women with abnormal cervical screening tests J Low Genit Tract Dis200711201ndash22 [Erratum in J Low Genit Tract Dis 2008 12 255]
[9] Kyrgiou M Koliopoulos G Martin-Hirsch P Arbyn M Prendiville WParaskevaidis E Obstetric outcomes after conservative treatment forintraepithelial or early invasive cervical lesions systematic review and meta-analysis Lancet 2006367489ndash98
[10] Sadler L Saftlas A Wang W Exeter M Whittaker J McCowan L Treatmentfor cervical intraepithelial neoplasia and risk of preterm delivery JAMA20042912100ndash6
[11] Samson SL Bentley JR Fahey TJ McKay DJ Gill GH The effect of loop electro-surgical excision procedure on future pregnancy outcome Obstet Gynecol2005105325ndash32
[12] Yabroff KRSaraiya M Meissner HI HaggstromDA Wideroff L Yuan G et al Special-ty differences in primary care physician reports of Papanicolaou test screeningpractices a national survey 2006 to 2007 Ann Intern Med 2009151602ndash11
[13] Lee JW Berkowitz Z Saraiya M Low-risk human papillomavirus testing and othernonrecommended human papillomavirus testing practices among US health careproviders Obstet Gynecol 20111184ndash13
[14] Roland KB Soman A Benard VB Saraiya M Human papillomavirus and Papanicolaoutests screening interval recommendations in the United States Am J Obstet Gynecol2011205447e1ndash8
[15] Saraiya M Berkowitz Z Yabroff KR Wideroff L Kobrin S Benard V Cervical cancerscreening with both human papillomavirus and Papanicolaou testing vsPapanicolaou testing alone what screeningintervals are physicians recommendingArch Intern Med 2010170977ndash85
[16] Wheeler CM Hunt WC Cuzick J et al A population-based study of human papillo-mavirus genotype prevalence in the United States baseline measures prior tomass human papillomavirus vaccination Int J Cancer Jan 1 2013132(1)198ndash207
[17] CastlePE SchiffmanM Wheeler CMSolomon D Evidence forfrequent regression of cervical intraepithelial neoplasia-grade 2 Obstet Gynecol 200911318ndash25
[18] Robertson AJ Anderson JM Beck JS et al Observer variability in histopathologicalreporting of cervical biopsy specimens J Clin Pathol 198942231ndash8
[19] Wright Jr TC MassadLS DuntonCJ SpitzerM Wilkinson EJSolomonD 2006AmericanSociety for Colposcopy and Cervical Pathology-sponsored Consensus Conference 2006consensus guidelines for the management of women with cervical intraepithelialneoplasia or adenocarcinoma in situ J Low Genit Tract Dis 200711223ndash39
[20] Pretorius RG Zhang WH Belinson JL et al Colposcopically directed biopsy randomcervical biopsy and endocervical curettage in the diagnosis of cervical intraepithelialneoplasia II or worse Am J Obstet Gynecol 2004191430ndash4
[21] Stoler MH Vichnin MD Ferenczy A et al FUTURE I II and III Investigators Theaccuracy of colposcopic biopsy analyses from the placebo arm of the Gardasilclinical trials Int J Cancer 20111281354ndash62
[22] Cox JT More questions about the accuracy of colposcopy what does this mean forcervical cancer prevention Obstet Gynecol 20081111266ndash7
[23] Pretorius RG Belinson JL Burchette RJ Hu S Zhang X Qiao YL Regardless of skillperforming more biopsies increases the sensitivity of colposcopy J Low GenitTract Dis 201115180ndash8
[24] Darragh TM Colgan TJ Cox JT et al LAST Project Work Groups The LowerAnogenital Squamous Terminology Standardization Project for HPV-Associated Le-sions background and consensus recommendations from the College of AmericanPathologists and the American Society for Colposcopy and Cervical Pathology JLow Genit Tract Dis 201216205ndash42
8 W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx
Pleasecite this article as KinneyW et al Cervical excisional treatment of young womenA population-based study Gynecol Oncol (2014) http dxdoiorg101016jygyno201312037
8132019 Cervical Excizional Treatement of Young Women
[8] Wright Jr TC Massad LS Dunton CJ Spitzer M Wilkinson EJ Solomon D 2006ASCCP-Sponsored Consensus Conference 2006 consensus guidelines for the man-agement of women with abnormal cervical screening tests J Low Genit Tract Dis200711201ndash22 [Erratum in J Low Genit Tract Dis 2008 12 255]
[9] Kyrgiou M Koliopoulos G Martin-Hirsch P Arbyn M Prendiville WParaskevaidis E Obstetric outcomes after conservative treatment forintraepithelial or early invasive cervical lesions systematic review and meta-analysis Lancet 2006367489ndash98
[10] Sadler L Saftlas A Wang W Exeter M Whittaker J McCowan L Treatmentfor cervical intraepithelial neoplasia and risk of preterm delivery JAMA20042912100ndash6
[11] Samson SL Bentley JR Fahey TJ McKay DJ Gill GH The effect of loop electro-surgical excision procedure on future pregnancy outcome Obstet Gynecol2005105325ndash32
[12] Yabroff KRSaraiya M Meissner HI HaggstromDA Wideroff L Yuan G et al Special-ty differences in primary care physician reports of Papanicolaou test screeningpractices a national survey 2006 to 2007 Ann Intern Med 2009151602ndash11
[13] Lee JW Berkowitz Z Saraiya M Low-risk human papillomavirus testing and othernonrecommended human papillomavirus testing practices among US health careproviders Obstet Gynecol 20111184ndash13
[14] Roland KB Soman A Benard VB Saraiya M Human papillomavirus and Papanicolaoutests screening interval recommendations in the United States Am J Obstet Gynecol2011205447e1ndash8
[15] Saraiya M Berkowitz Z Yabroff KR Wideroff L Kobrin S Benard V Cervical cancerscreening with both human papillomavirus and Papanicolaou testing vsPapanicolaou testing alone what screeningintervals are physicians recommendingArch Intern Med 2010170977ndash85
[16] Wheeler CM Hunt WC Cuzick J et al A population-based study of human papillo-mavirus genotype prevalence in the United States baseline measures prior tomass human papillomavirus vaccination Int J Cancer Jan 1 2013132(1)198ndash207
[17] CastlePE SchiffmanM Wheeler CMSolomon D Evidence forfrequent regression of cervical intraepithelial neoplasia-grade 2 Obstet Gynecol 200911318ndash25
[18] Robertson AJ Anderson JM Beck JS et al Observer variability in histopathologicalreporting of cervical biopsy specimens J Clin Pathol 198942231ndash8
[19] Wright Jr TC MassadLS DuntonCJ SpitzerM Wilkinson EJSolomonD 2006AmericanSociety for Colposcopy and Cervical Pathology-sponsored Consensus Conference 2006consensus guidelines for the management of women with cervical intraepithelialneoplasia or adenocarcinoma in situ J Low Genit Tract Dis 200711223ndash39
[20] Pretorius RG Zhang WH Belinson JL et al Colposcopically directed biopsy randomcervical biopsy and endocervical curettage in the diagnosis of cervical intraepithelialneoplasia II or worse Am J Obstet Gynecol 2004191430ndash4
[21] Stoler MH Vichnin MD Ferenczy A et al FUTURE I II and III Investigators Theaccuracy of colposcopic biopsy analyses from the placebo arm of the Gardasilclinical trials Int J Cancer 20111281354ndash62
[22] Cox JT More questions about the accuracy of colposcopy what does this mean forcervical cancer prevention Obstet Gynecol 20081111266ndash7
[23] Pretorius RG Belinson JL Burchette RJ Hu S Zhang X Qiao YL Regardless of skillperforming more biopsies increases the sensitivity of colposcopy J Low GenitTract Dis 201115180ndash8
[24] Darragh TM Colgan TJ Cox JT et al LAST Project Work Groups The LowerAnogenital Squamous Terminology Standardization Project for HPV-Associated Le-sions background and consensus recommendations from the College of AmericanPathologists and the American Society for Colposcopy and Cervical Pathology JLow Genit Tract Dis 201216205ndash42
8 W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx
Pleasecite this article as KinneyW et al Cervical excisional treatment of young womenA population-based study Gynecol Oncol (2014) http dxdoiorg101016jygyno201312037