18.Cervical Cancer

Cervical Dysplasia and Cervical Cancer

Qu [email protected] First Central Hospital

New Cases of Cervical Cancer per Year

459400Total

1570044000472003130036900131500716009700

703001200

105100354300

North AmericaLatin America

EuropeSoviet Union

AfricaChinaIndeaJapan

Asia（ Other Areas）Australia/New Zealand

Advanced AreasDeveloping Aeras

New CasesArea

(Parkin D.M,et al Bulletin of the WHO.1984,62:163-183)

Etiology and Epidemiology

HPV infection High risk factors Young age at first coitus(<20yr) Multiple sexual partners Sexual partner with multiple sexual partners Young age at first pregnancy High parity Lower socioeconomic status Smoking

•DS DNA

•No growth cell culture

LCR E6E7

E1

E2

E4E5L2

L1

HPV

HPV infection via HPV infection via wounds in epitheliumwounds in epithelium

Infection From Time of First Sexual Intercourse

From Winer RL, Lee S-K, Hughes JP, Adam DE, Kiviat NB, Koutsky LA. Genital human papillomavirus infection: incidence and risk factors in a cohort of female university students. Am J Epidemiol. 2003;157:218–226. Reprinted with the permission of Oxford University Press.

0 4 8 12 16 20 24 28 32 36 40 44 48 52 560

0.2

0.4

0.6

0.8

1

Months Since First Intercourse

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HP

V In

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ion

0

1

2

3

4

5

6

7

CIN Invasive Cervical Cancer

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tes

* ≥ 23 or Never18–22

≤ 17

*Mantle-Haenszel estimates adjusted for age only1. La Vecchia C, Franceschi S, DeCarli A, et al. Cancer. 1986;58:935–941.

Age at First Intercourse (Years)

(n=206) (n=327)

Cervical Intraepithelial Neoplasia

9,710 new cases of cervical cancer1

330,000 new cases of high-grade cervical dysplasia (CIN 2/3)2

1.4 million new cases of low-grade cervical dysplasia (CIN 1)2

1 million new cases of genital warts3

Incidence of HPV infection, CIN and Incidence of HPV infection, CIN and Cervical Cancer in USACervical Cancer in USA

Several Conceptions Cervical intraepithelial neoplasia(CIN) the condition

that different degree of abnormal epithelial proliferation and maturation above the basement membrane.

Transformation zone the area of metaplastic squamous epithelial located between the original squamocolumnar junction and new squamocolumnar junction.

Original squamocolumnar junction The junction between the embryologic squamous and columnar epithelia at or near the external cervical os is called the original squamocolumnar junction.

Before puberty

After puberty and reproductive period

child-bearing period

Peri-menopausal period

menopausal period

Classification of an abnormal papanicolaou smear(According to the standard of the 2001 Bethesda classification of cytologic abnormalities )

squamous epithelial cell abnormalities glandular epithelial cell abnormalities

Atypical squamous cells of undetermined significance (ASCUS) cannot exclude HSIL(ASC-H)

Low-grade squamous intraepithelial lesion(LSIL) encompassing:human papillomavirus/mild

High-grade squamous intraepithelial lesion(HSIL) encompassing:moderate and server dysplasia, carcinoma in situ; CIN2 and CIN3

Squamous cell carcinoma

Atypical glandular cells(AGC)(specify endocervical, endometrial, or not otherwise specified)

Atypical glandular cells, favor neoplastic (specify endocervical, or not otherwise specified)

Endocervical adenocarcinoma in situ(AIS)

Adenocarcinoma

Normal ASCUS LSIL HSIL

Conventional Pap Smear

Decrease

Sensitivity

Liquid-based Cytology

HPV infection and endocrine change

The Liquid-based Cytology

CIN 1 CIN2 CIN3

LSIL HSIL

Normal or benign disease Carcinoma in situ

Early invasive carcinoma

CIN

Pathology

Cytology

Colposcopy

At colposcopy, the original or native squamous epithelium appears gray and homogeneous. The columnar epithelium appears red and grapelike. The transformation zone can be identified by the presence of gland openings that are not covered by the squamous metaplasia and by the paler color of the metaplastic epithelium compared with the original squamous epithelium.Normal blood vessels branch like a tree.

Squamous epithelial Columnar epithelial

Squamous epithelial Columnar epithelial

(iodine test)

Biopsy and endocervical Curettage

A diagnostic cone biopsy of the cervix is indicated if : Colposcopic examination is unsatisfactory Endocervical curettings show a high-grade lesion Papanicolaou smear shows a high-grade lesion that is n

ot confirmed on punch biopsy Papanicolaou smear indicates adenocarcioma in situ Microinvasive is present on the punch biopsy

Pathology of CIN

CIN I CIN 2 CIN 3 carcinoma in situ

Treatment of intraepithelial neoplasia

Loop excision of the transformation LEEP,loop electrodiathermy excision procedure

Laser Cryosurgery Electrocoagulation Cervical conization Hysterectomy

Cervical carcinoma

Incidence of Cervical Cancer in China

New Cases 130,000/year

Died from CC 20,000~30,000/year

Incidence of CC has increased

tends to occur in younger

Incidence: 138.75/100,000 (8 million samIncidence: 138.75/100,000 (8 million samples, 25 provinces) ples, 25 provinces)

High incidence of Age: High incidence of Age: ≤ 35 4.8% (80’s) ≤ 35 4.8% (80’s) 34.1% (2000) 34.1% (2000)

Mortality: 10.28/100,000 (70’s)Mortality: 10.28/100,000 (70’s) 3.25/100,000 (90’s) 3.25/100,000 (90’s) 69% dropped 69% dropped

The presence of The presence of HPVHPV in virtually all in virtually all cercervical cancervical cancer implies the highest worldw implies the highest worldwide attributabe fraction so far reported foide attributabe fraction so far reported for a specific cause of any major human r a specific cause of any major human cancercancer

Pre-Invasive Cancer Invasive Cancer

Normal Pre-Invasive Cancer Invasive Cancer

Natural History of Cerical Carcinogenesis

Signs and Symptoms

Abnormal vaginal bleeding presents with postcoital, intermenstrual, or postmenopausal

vaginal bleeding. Abnormal vaginal discharge Advanced symptomes such as, pelvic

pain, leg swelling, and urinary frequency.

Physical finding General physical examination such as weight loss, enlar

ged inguinal lymph nodes, edema of the legs, ascites, pleural effusion, or hepatomegaly.

Pelvic examination In early cervical cancer may reveal a cervix that appears normal, especially if the lesion is endocervical. Visible disease may take several forms: ulcerative, exophytic, granular, or necrotic. The lesion may involve the upper potion of the vagina. The cervix may be distorted or completely replaced by tumor.

Rectovaginal examination Essential to determine the extent of involvement. The degree of cervical expansion and spread to the parametria are much more easily deteced with a finger in the rectum, as is extension into the uterosacral ligaments.

Laboratory test

Cervical squmous carcinoma

Cervical squmous carcinoma

Cervical squmous carcinoma

Three Steps Diagnosis for Cervical Carcinoma

Cytologic test Colposcopic test Cervical biopsy and Endocervical Curett

age

Pathologic features

Squamous carcinoma Adenocarcinoma Adenosquamous carcinomas Melanomas Sarcomas

Cervical squmous carcinoma

Cervical squmous carcinoma

Cervical adenocarcinoma

Cervical adenocarcinoma

Patterns of spread

Direct invasion cervical stroma, vagina, and parametrium.

Lymphatic spread pelvic and then paraaortic lymph nodes

Hematogenous spread such as lungs, liver, and bone

The International Federation of Gynecology and Obstetrics(FIGO) staging of cervical carcinoma

Stage Range

0 Carcinoma in situ, intraepithelial carcinoma

I The carcinoma is strictly confined to the cervix

Ia Invasive cancer is identified only microscopically. All grossslesions even with superficial invasion are Ib cancer. Invasion is limited to a measured stromal invasion, with a maximal depth 5 mm and a horizontal extension of not more than 7 mm

Ia1 Measured invasion of stroma not greater than 3 mm in depth and 7 mm in width

Ia2 Measured invasion of stroma greater than 3 mm and not greater than 5 mm and width not greater than 7 mm

Ib Clinical lesions confined to the cervix or preclinical lesions greater than stage Ia

Ib1 Clinical lesions not greater than 4 cm in size

Ib2 Clinical lesions greater than 4 cm in size

II The carcinoma extends beyond the cervix but has not extended to the pelvic wall or to the lower third of the vagina.

IIa No obvious parametrial involvement.

IIb Obvious parametrial involvement.

III The carcinoma has extended to the pelvic wall. On rectal examination there is no cancer-free space between the tumor and the pelvic wall. The tumor involves the lower third of the vagina. All cases with hydroeprosis or nonfunctioning kidney should be included, unless they are known to be due to another cause.

IIIa Tumor involves lower third of the vagina with no extension to the pelvic wall.

IIIb Extension onto the pelvic wall and /or hydronephrosis or nonfunctioning kidney.

IV The carcinoma has extended beyond the true pelvis or has clinically involved the mucosa of the bladder or rectum. A bullous edema, as such, does not permit a case to be allotted to stage IV

IVa Spread of the growth to adjacent organs.

IVb Spread to distant organs.

Preoperative investigations

Biopsies, cystoscopy, sigmoidoscopy, chest and skeletal radiographs, and liver function tests.

For patients with advanced disease, an abdominal and pelvic computed tomographic scan is helpful in planning management, but the results do not influence the FIGO stage.

Treatment of cervical cancer

Stage Ia (microinvasive cervical carcinoma) Operation radical hysterectomy and bilateral pelvi

c lymphadenectomy Radiation therapy intracavitary and external rad

iation. chemoradiation, using weekly cisplatin as the radiation sensitizer improve survival

Treatment of cervical cancerStage II Stage IIa radical surgery or chemoradiation therapy Stage IIb No operation. Combination of external beam chemo

radiation and intracavitary therapy. Stage III Stage IIIa and IIIb Chemoradiation therapy, usually externa

l beam followed by intracavity brachytherapy.Stage IV Stage IVa Pelvic chemoradiation therapy. Stage IVb Some pelvic radiation therapy to control bleeding

from the vagina, and chemotherapy is for distant metastases.

Prognosis for cervical cancer

Clinical stage Pathologocal type Adenocarcinoma and

adenosquamous carcinoma have a somewhat lower 5-year survival rate than squamous carcinoma, stage for stage.

Key points

Main cause for cervical carcinoma What is CIN, transformation zone How to differentiate CIN I, CIN II, CIN III? Diagnosis? Pathologic type? Patterns of spread in cervical carcinoma.

Questions 1

Which examination is the first step in cervical lesion

A. Cervical conizationB. Endocervical curettageC. Cervical pap smearD. ColposcopyE. Biopsy

Questions 2

Which patient should be treated by operation?

A. Stage IIIaB. Stage IVaC. Stage IIaD. Stage IIbE. Stage IIIb