Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 18-20: Carcinoma of the Cervix + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Increased risk in women who smoke and those with HIV or high-risk HPV types Gross lesions should be evaluated by colposcopically directed biopsies and not cytology alone +++ General Considerations ++ Can be considered a sexually transmitted disease Both squamous cell and adenocarcinoma of cervix are secondary to infection with the human papillomavirus (HPV), especially types 16 and 18 Women infected with HIV are at an increased risk for high-risk HPV infection and cervical intraepithelial neoplasia (CIN) Smoking appears to be a cofactor Squamous cell carcinoma (SCC) appears first in the intraepithelial layers (the preinvasive stage, or carcinoma in situ) +++ Demographics ++ Preinvasive cancer (CIN III) is a common diagnosis in women 25–40 years of age Incidence of cervical cancers SCC accounts for approximately 80% of cervical cancers Adenocarcinoma accounts for 15% Adenosquamous carcinoma, for 3–5% Neuroendocrine or small cell carcinomas are rare + Clinical Findings Download Section PDF Listen +++ +++ Symptoms and Signs ++ Often asymptomatic in early disease Most common signs Irregular or heaving bleeding Postcoital spotting Bladder and rectal dysfunction or fistulas and pain are late symptoms +++ Differential Diagnosis ++ Cervical intraepithelial neoplasia Cervical ectropion Cervical ectopy (columnar epithelium on face of os, common in adolescence) Genital warts (condyloma acuminata) Cervical polyp Cervicitis Nabothian cyst Granuloma inguinale + Diagnosis Download Section PDF Listen +++ +++ Laboratory Tests ++ Positive Papanicolaou smear +++ Imaging Studies ++ Further examinations, such as ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and lymphangiography are valuable for treatment planning +++ Diagnostic Procedures ++ Laparoscopy and fine-needle aspiration are also valuable for treatment planning Cervical biopsy and endocervical curettage, or conization These procedures are necessary steps after a positive Papanicolaou smear to determine the extent and depth of invasion of the cancer Even if the smear is positive, treatment is never justified until definitive diagnosis has been established through biopsy "Staging," or estimate of gross spread of cancer of the cervix The depth of penetration of the malignant cells beyond the basement membrane is a reliable clinical guide to the extent of primary cancer within the cervix and the likelihood of metastases It is customary to stage cancers of the cervix under anesthesia as shown in eTable 18–2 ++Table Graphic Jump LocationeTable 18–2.FIGO1 staging of cancer of the cervix.View Table||Download (.pdf)eTable 18–2. FIGO1 staging of cancer of the cervix. Preinvasive carcinoma Stage 0 Carcinoma in situ. Invasive carcinoma Stage I Carcinoma strictly confined to the cervix. IA Invasive cancer diagnosed only by microscopy. IA1 Measured invasion of stroma no > 3 mm in depth and no wider than 7 mm. IA2 Measured invasion of stroma > 3 mm in depth and no > 5 mm in depth and no wider than 7 mm. IB Clinical lesions confined to the cervix or preclinical lesions > 1A. All gross lesions, even with superficial invasion, are stage IB. IB1 Clinical lesions no > 4 cm. IB2 Clinical lesions > 4 cm. Stage II Carcinoma extends beyond the cervix but has not extended to the pelvic wall. The carcinoma involves the vagina but not as far as the lower third. IIA No obvious parametrial involvement. IIB Obvious parametrial involvement. Stage III Carcinoma has extended either to the lower third of the vagina or to the pelvic sidewall. All cases of hydronephrosis. IIIA Involvement of lower third of vagina. No extension to pelvic sidewall. IIIB Extension onto the pelvic wall and/or hydronephrosis or nonfunctioning kidney. Stage IV Carcinoma extended beyond the true pelvis or clinically involving the mucosa of the bladder or rectum. IVA Spread of growth to adjacent organs. IVB Spread of growth to distant organs. 1International Federation of Gynecology and Obstetrics. + Treatment Download Section PDF Listen +++ ++ Carcinoma in situ (stage 0) In women for whom childbearing is not a consideration, total hysterectomy is the definitive treatment In women who wish to retain the uterus, acceptable alternatives include cryosurgery, laser surgery, loop electrosurgical excision procedure (LEEP), or cervical conization Invasive carcinoma Microinvasive carcinoma (stage IA1) is treated with simple, extrafascial hysterectomy Stage IA2, IB1, and IIA cancers may be treated with either radical hysterectomy with concomitant radiation and chemotherapy or with radiation plus chemotherapy alone Stage IB1 may be treated with fertility-sparing surgery that includes radical trachelectomy and lymph node dissection with preservation of the uterus and ovaries Stage IB2, IIB, III, and IV cancers must be treated with radiation therapy plus chemotherapy Emergency measures for vaginal hemorrhage Originates from gross ulceration and cavitation in later stage cervical carcinoma Ligation and suturing of the cervix are usually not feasible However, emergent vaginal packing, cautery, tranexamic acid, and irradiation are helpful to stop bleeding temporarily Ligation, resection, or embolization of the uterine or hypogastric arteries may be lifesaving when other measures fail + Outcome Download Section PDF Listen +++ +++ Follow-Up ++ Follow-up co-testing (cytology and HPV DNA) should be repeated at 12-month intervals for 2 years after excisional or ablative treatment +++ Complications ++ Metastases to regional lymph nodes occur with increasing frequency from stage I to stage IV The ureters may become obstructed lateral to the cervix, causing hydroureter, hydronephrosis, and impaired kidney function Almost two-thirds of untreated patients die of uremia when ureteral obstruction is bilateral Pain in the back, in the distribution of the lumbosacral plexus, is often indicative of neurologic involvement Gross edema of the legs may be indicative of vascular and lymphatic stasis due to tumor Vaginal fistulas erode into the rectum and urinary tract 10–20% of patients with extensive invasive carcinoma die of hemorrhage +++ Prognosis ++ Two to 10 years are required for carcinoma to penetrate the basement membrane and invade the tissues Mortality has declined steadily due to high rates of screening and improved treatment The overall 5-year relative survival rate is 68% in white women and 55% in black women in the United States Survival rates are inversely proportional to the stage of cancer Stage 0, 99–100% Stage IA, > 95% Stage IB–IIA, 80–90% Stage IIB, 65% Stage III, 40% Stage IV, < 20% +++ Prevention ++ Regular Papanicolaou smears Smoking cessation Recombinant HPV vaccinations, given at 0, 1–2, and 6 months 4-valent vaccine (Gardasil) can prevent cervical cancer caused by HPV types 16 and 18 Can protect against low-grade and precancerous lesions caused by HPV types 6, 11, 16, and 18 9-valent vaccine (Gardasil 9) can prevent against low-grade and precancerous lesions and cervical cancer caused by HPV types 16, 18, 31, 33, 45, 52, and 58 +++ When to Refer ++ All patients with invasive cervical cancer should be referred to a gynecologic oncologist + References Download Section PDF Listen +++ + +American Cancer Society. Survival rates for cervical cancer, by stage, January 3, 2020. https://www.cancer.org/cancer/cervical-cancer/detection-diagnosis-staging/survival.html + +Cantillo E et al. Less is more: minimally invasive and quality surgical management of gynecologic cancer. Obstet Gynecol Clin North Am. 2019 Mar;46(1):55–66. [PubMed: 30683266] + +Johnson CA et al. Cervical cancer: an overview of pathophysiology and management. Semin Oncol Nurs. 2019 Apr;35(2):166–74. [PubMed: 30878194] + +US Preventive Services Task Force; Curry SJ et al. Screening for cervical cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2018 Aug 21;320(7):674–86. [PubMed: 30140884] + +Van Dyne EA et al. Trends in human papillomavirus-associated cancers—United States, 1999–2015. MMWR Morb Mortal Wkly Rep. 2018 Aug 24;67(33):918–24. [PubMed: 30138307]