Cervical Cancer Screening and Treatment/Referral Algorithms

Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education

Duke Internal Medicine Residency Curriculum

Cervical Cancer Screening and

Treatment/Referral Algorithms

Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services


Learning Objectives

• The importance of screening• Who should be screened and how often • When screening should be discontinued• The management algorithm for ASC-US, ASC-H,

LSIL, HSIL, AGC, and malignant cells• The management algorithm for endometrial

cells, when blood or inflammation is present, when endocervical cells are not present, and an unsatisfactory specimen



Screening



Risk Factors for Cervical Cancer:• Early onset of sexual activity• Multiple sexual partners• History of HPV infection

– High risk types include: 16, 18, 31, 33, 35, 39, 45, 51, 52, 58, 59, and 68

• Intercourse with high-risk sexual partner (h/o with multiple sex partners or intercourse with someone with cervical CA)

• History of sexually transmitted diseases • Smoking

– Refer patients to smoking cessation programs if dysplasia is diagnosed



• High parity • Immunosuppression• Low socioeconomic status• Previous history of vulvar or vaginal squamous

dysplasia. • More than three years since last Pap• History of contraceptive hormone use• History of radiation exposure



Symptoms that should make you suspect cervical CA:

• Abnormal vaginal bleeding• Postcoital bleeding• Vaginal discharge that may be watery, mucoid, or

purulent and malodorous• Vaginal passage of urine or stool• Pelvic or lower back pain• DVT or leg edema• Urinary symptoms• Rectal obstruction



Pitfalls in performing Pap smear:• Inform patient to avoid douching, sexual intercourse and

insertion of tampons or medication into vagina 48hrs prior to Pap

• Avoid performing the Pap during patient menstrual period or when a patient is bleeding heavily.

• Lubricant may contaminate sample, therefore do not use lubricant on speculum (you may use water) or perform bimanual exam prior to Pap.



• Make sure cervix is visualized.• Obtain ectocervical samples before endocervical samples• Perform Pap before testing for STDs with swab.• If large amounts of vaginal discharge is present , remove

with a large swab prior to Pap.



USPSTF April 2003• It is strongly recommended that women, who have been

sexually active and have a cervix, should be screened. It is based on the observation that screening for cervical cancer by cervical cytology (Pap smear) decreases incidence and mortality from cervical CA.

• Screening should begin within 3 years of the onset of sexual activity or at age 21 and should be repeated at least every 3 years. (The rational for starting screening latest at age 21 is the high prevalence of sexual activity among US woman by that age and possibility for inaccurate sexual history by physician.)



• Women age 65 and older should not be routinely screened if they have had adequate screening in the past with normal Pap smears and are not in a high-risk group.

• Women who have had total hysterectomy for benign disease should not be screened.

• There is insufficient evidence for or against routine use of new techniques such as liquid-based cytology, computerized screening.

• There is insufficient evidence for or against routine use of HPV testing.



American Cancer Society (ACS) guidelines Nov 2002 which are supported by the American College of Obstetrics and Gynecology (ACOG)

• Screening should begin 3 years after intercourse begins or at age 21.

• Yearly Pap or q2 years liquid prep Pap (the rational for yearly screening is that the sensitivity for a single Pap test may only be 60-80%)

• In women 30 yrs or older with 3 consecutive normal Pap test screening may be decreased to every 2-3 years.



• Screening should be stopped in women 70 years or older with 3 consecutive normal Pap and no abnormal Paps in the past 10 years.

• Screening may be stopped in women who have had total hysterectomy but should continue in women with subtotal hysterectomy (Physician should confirm presence or absence of cervix either by records or visual inspection). Screening should continue if hysterectomy was for cervical cancer.



Screening in immunocompromised women

• Women who are immunocompromised (either by HIV infection or other mechanisms) should be screened twice in the first year of diagnosis and then annually.( if the results were normal).



• References:

• USPSTF Screening for cervical Cancer: recommendations and rationale. Rockville MD. : Agency for Healthcare Reseach and Quality (AHRQ): 2003 Jan 22.21p 32.

• Saslow et. al. American Cancer Society guideline for the early detection of cervical neoplasia and cancer. CA Cancer J Clin 2002 Nov-Dec;52(6):342-62.

• ACOG Practice Bulletin: clinical management guidelines for obstetrician-gynecologists. Number 45, August 2003. Cervical cytology screening (replaces committee opinion 152, March 1995).SO - Obstet Gynecol 2003 Aug;102(2):417-27.

• United States Preventive Services Task Force. Guide to Clinical Preventive Services, 2nd ed. Williams and Wilkins, Baltimore 1996; p.105.

• Uptodate version 13.2 screening for cervical cancer



Management Algorithms



Intraepithelial Abnormalities

• Squamous epithelial cell abnormalities– Atypical squamous cells of (ASC)

• Of undetermined significance (ASC-US)• Cannot exclude HSIL (ASC-H)

– Low grade intraepithelial lesions (LSIL)• Human Papillomavirus (HPV) changes• Mild dysplasia• Cervical intraepithelial neoplasia (CIN) grade I

– High grade intraepithelial lesions (HSIL)• Moderate to severe dysplasia• CIN II• CIN III• Carcinoma in situ

– Carcinoma



Intraepithelial Abnormalities

• Glandular cell abnormalities– Atypical glandular cells (AGC)

• Endocervical• Endometrial• Other glandular cells

– Endocervical adenocarcinoma in situ (AIS)– Adenocarcnoma

• Atypical epithelial cells– Used when squamous versus glandular origin is unable to e

determined



Atypical Squamous Cells of Undetermined Significance

ASC-US1

HPV DNAtesting

Repeat Pap in

4-6 months

Refer for colposcopy

+ High risk type

- High risktype


Pap in 1 year

Abnormal Normal


Repeat Pap in

4-6 months

Abnormal

Normal

Pap in 1 year


•HPV testing is the preferred approach, it is also the most cost effective management strategy for U.S. women2

•If immunosuppressed, colposcopy is the recommended approach

•If postmenopausal, with atrophy, perform Pap 7 days post 4 week treatment with intravaginal estrogen. Repeat Pap in 4-6 months. If normal, return to routine screening. If abnormal, refer for colposcopy.

•HPV DNA testing is 83-100% sensitive or CIN II or III

•Colposcopy is 96% sensitive and 48% specific for distinguishing abnormal from normal cervical tissue

•A single repeat Pap is 67-85% sensitive for CIN II or III



Atypical Squamous Cells, Cannot Exclude HSIL

ASC-H

Colposcopy

Since the cytology is suspicious for a high-grade lesion, the next step is colposcopy.



Low-grade Squamous Intraepithelial Lesions

• Adolescents and postmenopausal females may be managed similar to ASC-US since LSIL has been shown to regress in adolescents2 and postmenopausal woman have a low prevalence of HPV3.

• 15-30% with LSIL will have CIN II or III on biopsy.

LSIL1

Adolescentsor

PostmenopausalPregnant

Atrophic epithelium

Otherwise,refer for

colposcopy

ColposcopyPap in

6 months and 1 year

HPV test in 1 year

Abnormal

Normal

Colposcopy

Routine surveillance

High risk HPV type

Colposcopy

Colposcopy

Pap 7 days post 4w tx

with intravaginal estrogen

Normal

Pap in 4 -6 months

Abnormal

Abnormal

Colposcopy

Normal

Colposcopy

Routinesurveillance



High-grade Squamous Intraepithelial Lesions

• 1-2% chance of invasive cancer on biopsy

• 70-75% chance of CIN II or III on biopsy, therefore, when cytology reveals HSIL, the next step is colposcopy.

HSIL

Colposcopy +/- endocervical curretage



Atypical Glandular Cells

• 9-54% with AGC have CIN on biopsy• <1 to 9% have invasive carcinoma• Pap is 50-72% sensitive for glandular neoplasia• In one study, the detection rate of abnormal lesions was 3.1% with repeated Pap

versus 28.4% with colposcopic-directed biopsy and 29.7% with endometrial curettage2. Since repeat Pap is less sensitive than colposcopy for detecting glandular lesions, when cytology reveals AGC, the next step is colposcopy.

AGC1

Atypical endocervical cells, Atypical glandular cells NOS, or

Endocervical adencarcinoma in situ (AIS)

>35 years oldor

<35 with vaginal bleeding

Colposcopyand

Endocervical curretage

Colposcopy,Endocervical curretage,

andEndometrial biopsy

Atypical endometrial

cells

Endometrial biopsy

Atypical endocervical cells favor neoplastic

Colposcopy with directed biopsy



Malignant Cells

• Malignant cells from the ovary, fallopian tube, vagina, vulva, or peritoneum

Malignant cells

Refer to gynecology oncology



Endometrial Cells

• Due to the concern for endometrial cancer, when the cytology of a woman greater than 40 reveals endometrial cells, the next step is endometrial biopsy.

Endometrial cells

>40 years old

Endometrialbiopsy



Blood or Inflammation Present or Endocervical Cells Not Present

• More rapid follow-up is recommended in patients who are at higher risk for intraepithelial abnormalities

Blood or Inflammation presentor Endocervical Cells Not Present

Repeat Pap in 6 months if:If pregnant,

Repeat Pap post partumOtherwise,

Repeat Pap in 1 year

Previous Pap with ASC-USor worse

without 3 subsequent negative PapsImmunosuppressed

Previous Pap with unexplained

glandular abnormality

Positive high risk HPVwithin the past 12 month

Inability to visualizeor sample

the endocervical canal

Nonadherent



Unsatisfactory Pap specimen

• One study noted a significant number (16%) of patients who originally had unsatisfactory Pap specimens, ultimately were diagnosed with intraepithelial lesions or neoplasia2. Therefore, since unsatisfactory specimens are more likely to have abnormalities at follow-up, the next step for repeated unsatisfactory specimens is colonoscopy and/or biopsies.

Unsatisfactory specimen

Repeat Pap in 2-4 months

Unsatisfactory specimen

Colposcopy and/or biopsies



Questions



Questions:1) A 28 y/o woman with no significant past medical history comes

into your clinic to establish care. She is currently sexually active and has had 5 lifetime sexual partners .

Her last Pap was 2 yrs ago and was normal. She has had 3 consecutive normal Paps. Does she need to be screened for cervical CA? if yes at what interval?.

a) Yes, and screening should be yearly b) Yes, but in light of her prior normal Paps the interval can be

decreased to q2-3 yrsc) No, since she’s had 3 consecutive normal Paps screening can be

stopped.d) Yes, and since she has not been screened in the past 2 yrs she

should be screened twice this yr then if normal resume yearly screens.



2) A 22 y/o woman presents for routine health maintenance in your clinic. She is a graduate student at Duke business school and her past med hx is only sig for h/o depression. She is on an SSRI and denies being currently depressed. She is not currently sexually active and denies prior sexual activity.

As part of your routine heath maintenance does she need screening for cervical cancer? If yes why?

a) No she does not need screening for cervical cancer since she’s not currently sexually active

b) No, she does not need screening since she has never been sexually active.

c) Yes, although she is not currently sexually active, her sexual history may be incomplete

d) Yes , since every adult woman should be screened yearly regardless of sexual history



3) A 30 y/o woman with h/o HTN presents the acute care clinic with chief complaint of increased vagina discharge. She denies fever or chills or any other associated symptoms. She has not been sexually active for 8mths but has had 15 lifetime sexual partners. She has always used barrier protection with intercourse. As part of your physical exam you performed a pelvic exam which revealed copious discharge from the vagina but generally normal appearing cervix except from a small spot (<1cm) on the posterior cervix which appeared friable bleed easily as you were obtaining culture samples.

Which of the following is the most appropriate next step.

a) Evaluate her for possible STD and refer to her PCP for further evaluation since this is an acute care visit.

b) Evaluate her for possible STD and screen her for cervical CA by performing a Pap.

c) Evaluate her for possible STD and refer her to a gynecologist for biopsy of the cervical lesion

d) Evaluate her for possible STD and titrate her blood pressure meds if her BP is not at goal.



Answers:1) A is correct. Based on ACS screening recommendation B is incorrect because reducing frequency of screening is

recommended in those ages 30 or older. C is incorrect because cessation of screening after 3 consecutive normal pap is recommended only in those over 65y/o. D is incorrect because it describes the screening recommendation for pts with HIV after initial diagnosis.

2) C is correct. The rational was that in the US by age 21 most women are sexually active, also some women may have been victims of rape or sexual abuse and may not disclose this.

A and B are incorrect because both USPTF and ACS recommend screening start at age 21. D is incorrect because not all adult women need screening. For instance continued screening those over 65 who have not been sexually active and have had previous normal Pap is not recommended.

3) C is correct. The sensitivity for Pap smear is about 60-80%, therefore a pt with visible lesion should have the lesion biopsied. A, B and C are incorrect because they do not include obtaining a biopsy.



4. Fill in the blanks

ASC-US


Pap in 1 year


Repeat Pap in

4-6 months

Abnormal

Normal

Pap in 1 year




4. Answers

ASC-US

HPV DNAtesting

Repeat Pap in

4-6 months

+ High risk type

- High risktype


Pap in 1 year

Abnormal Normal


Repeat Pap in

4-6 months

Abnormal

Normal

Pap in 1 year






Low-grade Squamous Intraepithelial Lesions

PregnantAtrophic

epithelium

Otherwise,refer for

colposcopy

Colposcopy HPV test in 1 year

Abnormal

Normal

Colposcopy


High risk HPV type

Colposcopy

Normal

Abnormal

Abnormal

Colposcopy

Normal

Colposcopy

Routinesurveillance



5. Answers

Low-grade Squamous Intraepithelial LesionsAdolescents

orPostmenopausal

PregnantAtrophic

epithelium

Otherwise,refer for

colposcopy

ColposcopyPap in

6 months and 1 year

HPV test in 1 year

Abnormal

Normal

Colposcopy


High risk HPV type

Colposcopy

Colposcopy

Pap 7 days post 4w tx

with intravaginal estrogen

Normal

Pap in 4 -6 months

Abnormal

Abnormal

Colposcopy

Normal

Colposcopy

Routinesurveillance





>35 years old

or<35 with vaginal bleeding



Endometrial biopsy





6. Answers


Atypical endocervical cells, Atypical glandular cells NOS, or

Endocervical adencarcinoma in situ (AIS)

>35 years oldor

<35 with vaginal bleeding

Colposcopyand

Endocervical curretage



Atypical endometrial

cells

Endometrial biopsy












7. Answers





Previous Pap with ASC-USor worse

without 3 subsequent negative PapsImmunosuppressed

Previous Pap with unexplained

glandular abnormality

Positive high risk HPVwithin the past 12 month

Inability to visualizeor sample

the endocervical canal

Nonadherent



8. Fill in the Blank






8. Answer


Repeat Pap in 2-4 months





9 and 10. State the answers

9. A 23 year old with HIV (CD4 600 and VL 100), diagnosed 6 months ago, presents to the Health Department. She is not on HAART. She has a history of HSIL in 2003.

What treatment should she have received for HSIL?

10. Being the industrious resident that you are, you perform a Pap smear since immunocompromised patients should be screened twice in the first year of diagnosis. The results return as atypical squamous cells of undetermined significance.

What do you do next?



9. and 10. Answers

9. Colposcopy and endocervical curretage, unless a diagnostic excisional procedure was performed.

10. Immunosuppressed patients with ASC-US, regardless of CD4 count, HIV viral load, or antiretroviral therapy, should be referred for colposcopy.

Cervical Cancer Screening and Treatment/Referral Algorithms

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