Pre-invasive & Invasive Lesions of the Cervix http://crisbertcualteros.page.tl

Normal Cervix Cancer Cervical Intraepithelial Neoplasia (CIN) Carcinogenic Factors CIN I CIN II CIN III Carcinogenesis

Carcinogenesis Normal Cervix Cancer Cervical Intraepithelial Neoplasia (CIN) Carcinogenic Factors CIN I CIN II CIN III

Human Papilloma Virus

Predisposing Factors Human Papilloma Virus Infection High Grade ( invasive cancer) HPV type 16, 18 , 45, 56 Intermediate Grade (CIN II / III) HPV type 31, 33, 35, 51, 52 Low Grade (Condyloma a. / CIN I) HPV type 6, 11, 40, 41, 42

Human Papilloma Virus Infection

High Grade ( invasive cancer)

HPV type 16, 18 , 45, 56

Intermediate Grade (CIN II / III)

HPV type 31, 33, 35, 51, 52

Low Grade (Condyloma a. / CIN I)

HPV type 6, 11, 40, 41, 42

HPV E3 E1 E2 E4 E5 E6 E7 L1 L2 Human Genome p53 pRB Viral Genome Integration

E6 p53 DNA Repair Programmed Cell Death (Apoptosis) Viral Oncoprotein – Host Regulatory Protein Complex

E7 pRB Viral Oncoprotein – Host Regulatory Protein Complex S G2 M G1 G0 cell cycle

Predisposing Factors Sexual behavior Early age of first coitus Adolescent age group Time interval from menarche Active cellular proliferation of the transformation zone

Sexual behavior

Early age of first coitus

Adolescent age group

Time interval from menarche

Active cellular proliferation of the transformation zone

Predisposing Factors Sexual behavior Multiple sexual partners Higher risk of HPV infection Likely to have first coitus at an early age Epidemiologic studies: rare in celibate women

Sexual behavior

Multiple sexual partners

Higher risk of HPV infection

Likely to have first coitus at an early age

Epidemiologic studies: rare in celibate women

Normal CANCER INITIATOR PROMOTER Carcinogenesis

Predisposing Factors Oral Contraceptive Pills Less likely to use barrier method Screening bias: more likely to be seen by a physician regularly Associated with Adenocarcinoma

Oral Contraceptive Pills

Less likely to use barrier method

Screening bias: more likely to be seen by a physician regularly

Associated with Adenocarcinoma

Predisposing Factors Sexual behavior Male factor Multiple sexual partner Uncircumcized

Sexual behavior

Male factor

Multiple sexual partner

Uncircumcized

Cervical Intraepithelial Neoplasia

Cervical Intraepithelial Neoplasia Pathology Nuclear aneuploidy Abnormal mitotic figures Loss of maturation of the epithelium *Dysplasia CONFINED to the epithelium

Pathology

Nuclear aneuploidy

Abnormal mitotic figures

Loss of maturation of the epithelium

*Dysplasia CONFINED to the epithelium

Cervical Intraepithelial Neoplasia Subtypes CIN I – 1/3 involved CIN II – 1/3 – 2/3 involved CIN III – 2/3 – whole epithelium

Subtypes

CIN I – 1/3 involved

CIN II – 1/3 – 2/3 involved

CIN III – 2/3 – whole epithelium

Cervical Intraepithelial Neoplasia Screening Tools Cytology ( Papanicolau smear) Colposcopy HPV DNA Typing

Screening Tools

Cytology ( Papanicolau smear)

Colposcopy

HPV DNA Typing

Cervical Intraepithelial Neoplasia Pap Smear “ Normal tissue sheds normal cells, abnormal tissue sheds abnormal cells “ Samples from the ENDOCERVIX and ECTOCERVIX

Pap Smear

“ Normal tissue sheds normal cells, abnormal tissue sheds abnormal cells “

Samples from the ENDOCERVIX

and ECTOCERVIX

Cervical Intraepithelial Neoplasia Steps in Doing the Pap Smear Insert the speculum lubricated with water only Visualize the cervix and vagina Sample the endocervix and ectocervix separately Spread sample thinly on a labelled glass slide Fix sample immediately with 95% ethanol Send sample to cytopathologist

Steps in Doing the Pap Smear

Insert the speculum lubricated with water only

Visualize the cervix and vagina

Sample the endocervix and ectocervix separately

Spread sample thinly on a labelled glass slide

Fix sample immediately with 95% ethanol

Send sample to cytopathologist

Cervical Intraepithelial Neoplasia Pap Smear Recommendation: Yearly pap smear for women who are sexually active. Then less frequent thereafter if with two successive normal results.

Pap Smear

Recommendation:

Yearly pap smear for women who are sexually active. Then less frequent thereafter if with two successive normal results.

Cervical Intraepithelial Neoplasia Pap Smear Instructions for the patients: No sexual intercourse a day before the smear Do not do vaginal douching or use any vaginal lubricant a day before the smear No vaginal bleeding (menstruation, etc.)

Pap Smear

Instructions for the patients:

No sexual intercourse a day before the smear

Do not do vaginal douching or use any vaginal lubricant a day before the smear

No vaginal bleeding (menstruation, etc.)

Cervical Intraepithelial Neoplasia Pap Smear Bethesda System (cytopathology report) Normal Benign cellular changes Infection Atypical cells of Undetermined significance (ASCUS)

Pap Smear

Bethesda System (cytopathology report)

Normal

Benign cellular changes

Infection

Atypical cells of Undetermined significance (ASCUS)

Cervical Intraepithelial Neoplasia Pap Smear (Bethesda System) Low Grade Squamous Intraepithelial Lesion (LSIL) HPV infection CIN I High Grade Squamous Intraepithelial Lesion (HSIL) CIN II CIN III Glandular Cell Abnormalities

Pap Smear (Bethesda System)

Low Grade Squamous Intraepithelial Lesion (LSIL)

HPV infection

CIN I

High Grade Squamous Intraepithelial Lesion (HSIL)

CIN II

CIN III

Glandular Cell Abnormalities

Cervical Intraepithelial Neoplasia Pap Smear Pitfalls: Sampling error (bloody, inadequate cells, etc.) Poor fixation of sample (dry smear) Skill of cytopathologist

Pap Smear

Pitfalls:

Sampling error (bloody, inadequate cells, etc.)

Poor fixation of sample (dry smear)

Skill of cytopathologist

Colposcopy

Cervical Intraepithelial Neoplasia Colposcopy Clinical evaluation of the biochemical and metabolic changes in the cervix as reflected by changes in the: Topography of the epithelial surfaces Vascular architecture

Colposcopy

Clinical evaluation of the biochemical and metabolic changes in the cervix as reflected by changes in the:

Topography of the epithelial surfaces

Vascular architecture

Colposcopy of the Cervix

Cervical Intraepithelial Neoplasia Colposcopy Indications: Abnormal cervical cytology Clinically suspicious cervix Women with high risk factors for cervical abnormalities Women with genital warts or HPV infection Women exposed to carcinogens (DES, etc.)

Colposcopy

Indications:

Abnormal cervical cytology

Clinically suspicious cervix

Women with high risk factors for cervical abnormalities

Women with genital warts or HPV infection

Women exposed to carcinogens (DES, etc.)

Cervical Intraepithelial Neoplasia HPV DNA Typing PCR – most sensitive test Prevalence of HPV is dependent on: age sexual activity laboratory technique frequency of testing

HPV DNA Typing

PCR – most sensitive test

Prevalence of HPV is dependent on:

age

sexual activity

laboratory technique

frequency of testing

Cervical Intraepithelial Neoplasia Management Cryotherapy Ablative procedures LEEP / Conization Hysterectomy

Management

Cryotherapy

Ablative procedures

LEEP / Conization

Hysterectomy

Cervical Carcinoma

Cervical Carcinoma PUBLIC HEALTH CONCERN Most common gynecologic cancer Top 5 - Most common cancer in women Top 5 - Most common cause of cancer death in women Majority present at advanced stage

PUBLIC HEALTH CONCERN

Most common gynecologic cancer

Top 5 - Most common cancer in women

Top 5 - Most common cause of cancer death in women

Majority present at advanced stage

Cervical Carcinoma Pathology Epithelial Tumors Squamous Cell Carcinoma Large cell, non keratinizing Large cell, keratinizing Verrucous Carcinoma Adenosquamous Carcinoma Glassy Cell Carcinoma Adenoid Cystic Carcinoma Adenoid Basal Epithelioma

Pathology

Epithelial Tumors

Squamous Cell Carcinoma

Large cell, non keratinizing

Large cell, keratinizing

Verrucous Carcinoma

Adenosquamous Carcinoma

Glassy Cell Carcinoma

Adenoid Cystic Carcinoma

Adenoid Basal Epithelioma

Cervical Carcinoma Pathology Epithelial Tumors (Adenocarcinoma) Mucinous Mesonephric Endometrioid Clear Cell Villoglandular Papillary Serous Minimal deviation

Pathology

Epithelial Tumors (Adenocarcinoma)

Mucinous

Mesonephric

Endometrioid

Clear Cell

Villoglandular

Papillary Serous

Minimal deviation

Cervical Carcinoma Pathology Neuroendocrine Tumors Small Cell Carcinoma Large Cell Carcinoma Carcinoid Tumors Typical Atypical

Pathology

Neuroendocrine Tumors

Small Cell Carcinoma

Large Cell Carcinoma

Carcinoid Tumors

Typical

Atypical

Cervical Carcinoma Symptoms & Pattern of Spread Symptoms Vaginal bleeding Foul smelling vaginal discharge Pelvic pain Leg edema

Symptoms & Pattern of Spread

Symptoms

Vaginal bleeding

Foul smelling vaginal discharge

Pelvic pain

Leg edema

Cervical Carcinoma Symptoms & Pattern of Spread Pattern of Spread Direct invasion of adjacent structures Lymphatic invasion Hematogenous

Symptoms & Pattern of Spread

Pattern of Spread

Direct invasion of adjacent structures

Lymphatic invasion

Hematogenous

Cervical Carcinoma Diagnosis & Staging Pelvic examination & Cervical Biopsy Chest x-ray Colposcopy Cystoscopy Proctosigmoidoscopy Intravenous pyelogram Barium enema

Diagnosis & Staging

Pelvic examination & Cervical Biopsy

Chest x-ray

Colposcopy

Cystoscopy

Proctosigmoidoscopy

Intravenous pyelogram

Barium enema

Cervical Carcinoma Diagnosis & Staging Other tes ts CT Scan MRI PET Scan Laparoscopy / hysteroscopy Lymphography

Diagnosis & Staging

Other tes ts

CT Scan

MRI

PET Scan

Laparoscopy / hysteroscopy

Lymphography

Cervical Carcinoma Staging Stage I – Carcinoma confined to the cervix I A – Microinvasive carcinoma IA 1 – Stromal invasion < / = 3.0 mm in depth and < / =7.0 mm in horizontal dimension IA 2 – Stromal invasion > 3.0 mm in depth and > 7.0 mm in horizontal dimension

Staging

Stage I – Carcinoma confined to the cervix

I A – Microinvasive carcinoma

IA 1 – Stromal invasion < / = 3.0 mm in depth and < / =7.0 mm in horizontal dimension

IA 2 – Stromal invasion > 3.0 mm in depth and > 7.0 mm in horizontal dimension

Cervical Carcinoma Staging Stage I – Carcinoma confined to the cervix I B – Clinically visible lesion IB 1 – lesion < / = 4 cms. IB 2 - lesion > 4 cms.

Staging

Stage I – Carcinoma confined to the cervix

I B – Clinically visible lesion

IB 1 – lesion < / = 4 cms.

IB 2 - lesion > 4 cms.

Cervical Carcinoma Staging Stage II – Carcinoma invades beyond the uterus, but not to the pelvic wall or to the lower vagina. II A – No parametrial involvement II B – With parametrial involvement

Staging

Stage II – Carcinoma invades beyond the uterus, but not to the pelvic wall or to the lower vagina.

II A – No parametrial involvement

II B – With parametrial involvement

Cervical Carcinoma Staging Stage III – Carcinoma extends to the pelvic wall and / or involves the lower third of the vagina or causes hydronephrosis or nonfunctioning kidney. III A – Involves lower third of vagina with no extension to the pelvic wall III B – With extension to the pelvic wall and / or hydronephrosis or nonfunctioning kidney

Staging

Stage III – Carcinoma extends to the pelvic wall and / or involves the lower third of the vagina or causes hydronephrosis or nonfunctioning kidney.

III A – Involves lower third of vagina with no extension to the pelvic wall III B – With extension to the pelvic wall and / or hydronephrosis or nonfunctioning kidney

Cervical Carcinoma Staging Stage IV – Carcinoma extends beyond the true pelvis or has involved the mucosa of the bladder or rectum (biopsy proven) IV A – Spread to adjacent organs IV B – Spread to distant organs

Staging

Stage IV – Carcinoma extends beyond the true pelvis or has involved the mucosa of the bladder or rectum (biopsy proven)

IV A – Spread to adjacent organs

IV B – Spread to distant organs

Stage III A Stage III B Extension to the LOWER 3rd of Vagina Extension to the PELVIC WALL

Surgical Management

Cervical Carcinoma Surgical Management Stage IA 1 – Extrafascial Hysterectomy Stage IA 2 to IB 1 and II A Radical Hysterectomy with pelvic lymphadenectomy

Surgical Management

Stage IA 1 – Extrafascial Hysterectomy

Stage IA 2 to IB 1 and II A

Radical Hysterectomy with

pelvic lymphadenectomy

Cervical Carcinoma Surgical Management Advantages Extent of metastasis evaluated Ovaries preserved in young patients Treatment duration is short Psychological benefit Sexual function not impaired

Surgical Management

Advantages

Extent of metastasis evaluated

Ovaries preserved in young patients

Treatment duration is short

Psychological benefit

Sexual function not impaired

Cervical Carcinoma Surgical Management Complications Hemorrhage Injury to the ureter and adjacent organs Infection Fistula and lymphocyst formation

Surgical Management

Complications

Hemorrhage

Injury to the ureter and adjacent organs

Infection

Fistula and lymphocyst formation

Multimodality Treatment

MultiModality Treatment Combination Platinum based chemotherapy AND Radiotherapy Chemotherapy: - Cisplatin - given weekly or every three weeks Radiotherapy: - External Radiation ( Cobalt, Lin-Acc) - Brachytherapy

Combination Platinum based chemotherapy AND Radiotherapy

Chemotherapy:

- Cisplatin

- given weekly or every three weeks

Radiotherapy:

- External Radiation ( Cobalt, Lin-Acc)

- Brachytherapy

Cervical Carcinoma Cervical Carcinoma in Pregnancy The response to treatment and prognosis of the cancer is not affected by the pregnancy and vice-versa Management dependent on the age of gestation of the pregnancy and stage of the cervical cancer

Cervical Carcinoma in Pregnancy

The response to treatment and prognosis of the cancer is not affected by the pregnancy and vice-versa

Management dependent on the age of gestation of the pregnancy and stage of the cervical cancer

Cervical Carcinoma in Pregnancy Management ChemoRT Stage IB2, IIB, III & IV RHBLND Stage IA2, IB1 & IIA < 20 weeks Management Stage of Cancer Age of Gestation

Management

Cervical Carcinoma in Pregnancy Management * Once with fetal lung maturity CS* + ChemoRT postpartum Stage IB2, IIB, III & IV CS* + RHBLND Stage IA2, 1B1 & IIA >20 weeks Management Stage of Cancer Age of Gestation

Management

Follow-Up

Cervical Carcinoma Follow-up Monthly follow-up for the first year and bi-monthly on the second year Pap smear every 3 – 6 months Chest X-ray every year Other imaging studies – dependent on clinical suspicion of recurrence

Follow-up

Monthly follow-up for the first year and bi-monthly on the second year

Pap smear every 3 – 6 months

Chest X-ray every year

Other imaging studies – dependent on clinical suspicion of recurrence

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