Cervical Cancer & Pap Smears E.Naghshineh MD

Epidemiology 16,000 cases / year Incidence  but mortality from cervical cancer  over the past 50 years Cervical CA is still the 7th most common cancer in females and the 8th most common cause of death E.Naghshine MD

Etiology Human Papiloma Virus (HPV) + an unidentified co-carcinogen E.Naghshine MD

Risk Factors Multiple sexual partners (> 1) Promiscuous partner Age of first intercourse experience Early childbearing Prior STDs (HSV II, genital warts, vaginal infections) Cigarette Smoking Oral Contraceptive usage Intrauterine exposure to DES Immunodeficiency E.Naghshine MD

Age of Onset Carcinoma In-Stiu (CIS) 30 years Cervical Intraepithelial Neoplasia (CIN) 35 years Invasive Cervical Cancer 45 years E.Naghshine MD

Histological Types Squamous Cell Carcinoma 80-95% Adenocarcinoma 5-20% Other: Clear cell, sarcomas E.Naghshine MD

Symptoms CIN: Asymptomatic Invasive Cancer No classic presentation May present with abnormal vaginal bleeding May present with postcoital bleeding E.Naghshine MD

Physical Exam CIN Invasive Cancer Advanced Cancer Cervix appears normal to general inspection Invasive Cancer Exophytic growth seen on cervix Growth: Cauliflower-like, friable, deeply ulcerated Advanced Cancer Pelvic Masses Palpable E.Naghshine MD

Metastasis Morbidity and Mortality associated with regional spread of the cancer Spreads to pelvic nodes, ureters, bladder, rectum. Dangerous when cancer blocks ureters resulting in uremia --> death Hematogenous spread- uncommon E.Naghshine MD

Pathogenesis Site where squamous epithelium of vagina meets columnar epithelium of endocervix known as squamocolumnar junction (SCJ) Before puberty: SCJ located just inside the cervical os At puberty, increasing levels of estrogen lead to squamous metaplasia of columnar epithelium to squamous epithelium Results in repositioning of the SCJ further towards the uterus E.Naghshine MD

Pathogenesis (2) Region between the old and new SCJs known as the transformation zone Transformation zone is the site of 95% of the cervical cancer development Since zone is located within the cervical os, unable to be viewed during routine pelvic exam Exposure of transformation zone to carcinogens begins process of intraepithelial neoplasia While exact role of carcinogens in this process remains poorly understood, it is clear that HPV and cigarette smoking can cause dysplasia at the transformation zone E.Naghshine MD

Human Papiloma Virus (HPV) Certain types of HPV are responsible for genital warts, others for dysplasia/cancer HPV Types 6 & 11 associated with development of genital warts Types 16,18,31,33,35,39,45,51,52,56,58 associated with development of dysplasia/cancer E.Naghshine MD

Pap Smears Strong sensitivity and specificity Accuracy of Smear Requires adequate sample presence of enough inflamation and dysplasia quick fixation of specimen to glass slide E.Naghshine MD

When to Get Pap Smears? ACOG Recommendations 1st Pap Smear at age when patient becomes sexually active (or by age 18) Yearly pap smears thereafter Others contend that monogamous women with no history of abnormal pap smears can have them done every 3 years E.Naghshine MD

Performing Pap Smear Patient asked to lie on her back at edge of exam table with feet in stirrups Metal or plastic speculum is inserted into vagina to expand the wall of vagina to enable access to cervix Cells are collected using cotton swab, wooden spatula, or cervical brush and smeared onto glass slide Preservative sprayed to prevent cells from drying and artifacts from forming Slide evaluated by lab technician who looks for abnormalities in the 50,000 to 300,000 cells on slide E.Naghshine MD

Pap Smear Classification Systems The Class System (I to V) The CIN System (CIN I to III) characterizes the degree of cellular abnormalities The SIL System (Bethesda System) Lesions characterized as LGSIL or HGSIL Presence of HPV noted This scheme is most widely used system these days E.Naghshine MD

Evaluating the Pap Smear First, the smear is evaluated for adequacy of sample Secondly the sample is categorized as “normal” or “other” Lastly, all sample categorized as “other” are further specified as infection, inflammation, or various stages of cancer E.Naghshine MD

What to Inform Patients Prior to Obtaining Pap Smear? No douching or usage of vaginal medications, lubricants, or spermicides within 2-3 days of exam (these products may hide abnormal cells) Schedule Pap Smear between days 12-16 of menstrual cycle, if possible Abstain from intercourse 1-2 days prior to smear E.Naghshine MD

Pitfalls of Diagnosing Cervical Cancer 30% of cases of cervical cancer are missed due to errors interpreting results of pap smears Ways of Improving Pap Smears rescreen portions of slide deemed negative to reduce false-negatives new liquid smears may be have higher sensitivty and specificity usage of computerized devices to analyze smear (PAPNET, VIRAPAP) E.Naghshine MD

Improving Access to Pap Smears 50% of patients who die of cervical cancer have never had a Pap Smear Uninsured, minorities, older patients and those who live in rural areas have limited access to Pap Smears These groups must be targeted to further reduce rates of cervical cancer in the US E.Naghshine MD

Precursor Lesions Reason for thorough classification schemes for intraepithelial lesions is to determine the likelihood of such lesions progressing to overt cancer Usual progression from mild dysplasia to overt cancer takes 7-8 years Precursor lesions characterized as mild dysplasia have 65% chance of spontaneously regressing, 20% chance of remaining the same, 15% chance of worsening E.Naghshine MD

Precursor Lesions (2) Unfortunately, we are unable to predict with much accuracy, which lesions will regress and which will worsen over time For this reason, ACOG recommends any patient with a mildly abnormal smear undergo further evaluation with culposcopy and/or biopsy E.Naghshine MD

Culposcopy Culposcope: A stereomicroscope that enables investigators to examine areas of dysplasia and select best sites to biopsy device has green filter that helps identify presence of blood vessels (an ominous sign) Before culposcopy, cervix coated with acetic acid which enhances presence of dysplasia Key to culposcopy is complete visualization of transformation zone E.Naghshine MD

Cone Biopsy Reasons for Performing Cone Biopsy Investigator is unable to visualize the entire transformation zone Endocervical curretage shows dysplastic changes Results of Pap Smear are remarkably different than results from culposcopy Cone biopsy is a minor surgical procedure to further investigate the transformation zone Performed using a scalpel or laser E.Naghshine MD

Treatment of CIN Most effective treatment is excision of precursor lesions Ways to Remove Lesions Cryocautery- freezing, thawing, & refreezing lesion Culposcopic Laser Therapy- more accurate, capable of removing low and high grade lesions Excisional Biopsy- performed on low grade lesion Always schedule follow-up Pap Smears to assure lesions have not returned E.Naghshine MD

Managing Cervical Cancer All visible lesions should be biopsied Lesions must be properly staged to determine whether cancer has spread and help determine therapeutic approach Cervical Cancer spreads by lymphatics or direct invasion Lymphatic Spread: Cervical/paracervical nodes  regional nodes  deep pelvic nodes Direct spread: To bladder, vagina, parametria, rectum CT Scan helpful in assessing cancer that has spread E.Naghshine MD

Treatment of Invasive Cervical Cancer Option 1: Surgery Useful in patients with Stage I and II cancer Radical hysterectomy is procedure of choice for overt cancer When performing surgery, spare ovaries so they can continue to manufacture estrogen Potential pitfalls of surgery: hemorrhage, damage to nerves supplying bladder, formation of fistula E.Naghshine MD

Treatment of Cervical Cancer Option 2: Radiation Reserved for poor surgical candidates or patients with advanced disease Problems with radiation- infertility, radiation cystitis, fibrosis Usually ineffective in patients with recurrent cervical cancer E.Naghshine MD

Prognosis Patients with CIS and cancer limited to cervix- cure rate 90-100% Patients with advanced cervical cancer- cure rate is 25-50% E.Naghshine MD

Reasons for Such Good Prognosis for Cervical Cancer Presence of an easily identifiable precursor lesion Slow progression of cancer Access to cheap non-invasive diagnostic tools (Pap Smears and Culposcopy) Simple and effective treatments E.Naghshine MD