3.5 Gynecologic Malignancies: Endometrial, Ovarian, Cervical, Vulvar & Vaginal Cancers
Key Takeaways
Endometrial cancer is the most common gynecologic cancer in the United States; about 90% of cases present with postmenopausal or abnormal bleeding, and endometrial sampling is the key first test.
Obesity, unopposed estrogen, chronic anovulation (PCOS), tamoxifen, diabetes, and Lynch syndrome raise endometrial cancer risk; combined hormonal contraception and the LNG-IUS lower it.
Ovarian cancer is the deadliest gynecologic cancer, often presenting with vague bloating, early satiety, and pelvic pain; the USPSTF recommends against screening average-risk women with CA-125 or ultrasound.
Germ cell ovarian tumors affect young women and produce tumor markers: LDH in dysgerminoma, AFP in yolk sac tumor, and hCG in choriocarcinoma.
Any persistent vulvar lesion, especially within lichen sclerosus, needs biopsy because HPV-independent vulvar squamous cell carcinoma arises from differentiated VIN.
Overview for the WHNP
WHNPs rarely treat gynecologic cancers, but the exam tests whether you recognize warning signs, choose the correct first diagnostic step, and refer appropriately to gynecologic oncology. Early detection is the WHNP's main contribution to survival.
| Cancer | Key Risk Factors | Classic Presentation | First Step |
|---|---|---|---|
| Endometrial | Obesity, unopposed estrogen, PCOS, tamoxifen, diabetes, nulliparity, Lynch syndrome | Postmenopausal bleeding; abnormal bleeding at 45 or older | TVUS stripe or endometrial biopsy |
| Ovarian | Age, BRCA1/2, Lynch, endometriosis, nulliparity | Bloating, early satiety, pelvic pain, urinary urgency, adnexal mass | TVUS and CA-125 (postmenopausal); gynecologic oncology referral |
| Cervical | Persistent high-risk HPV, smoking, HIV, no screening | Postcoital bleeding, discharge, visible lesion | Biopsy of any visible lesion |
| Vulvar | Older age, lichen sclerosus, HPV, smoking | Pruritus, plaque, ulcer, or mass | Punch biopsy |
| Vaginal | HPV, prior cervical neoplasia, in utero DES exposure | Bleeding, discharge, mass | Biopsy |
Endometrial Cancer
Endometrial cancer is the most common gynecologic cancer in the United States, and both incidence and mortality have been rising, with a disproportionate mortality burden among Black women.
- Endometrioid (traditionally "type I") tumors are estrogen-driven, often preceded by endometrial intraepithelial neoplasia (atypical hyperplasia), and usually low grade.
- Non-endometrioid ("type II") tumors (serous, clear cell, carcinosarcoma) are not estrogen-related, occur in older women, and behave aggressively. FIGO's 2023 staging adds molecular classes (POLE-mutated, mismatch repair–deficient, p53-abnormal, and no specific molecular profile).
- Presentation: About 90% present with postmenopausal bleeding or abnormal bleeding, so most are found early.
- Evaluation: In postmenopausal bleeding, an endometrial thickness of 4 mm or less on TVUS has a high negative predictive value, but persistent bleeding needs sampling regardless. Endometrial biopsy is the standard office test.
- Atypical hyperplasia/EIN: Treated with hysterectomy because up to about 40% have concurrent cancer; progestin therapy (often the LNG-IUS) with surveillance is an option when fertility is desired.
- Protective factors: Combined hormonal contraceptives (protection persists for years after stopping), the LNG-IUS, pregnancy, and physical activity.
- Lynch syndrome: Mismatch-repair gene variants (MLH1, MSH2, MSH6, PMS2) carry a lifetime endometrial cancer risk of up to roughly 40%–60% depending on the gene, plus colorectal and ovarian risk. All endometrial cancers are now tested for mismatch-repair status.
Ovarian Cancer
Ovarian cancer is the most lethal gynecologic cancer because most cases are diagnosed at an advanced stage.
Tumor Types
| Category | Typical Patient | Key Features and Markers |
|---|---|---|
| Epithelial (about 90%) | Older women | High-grade serous is most common and often arises in the fallopian tube; CA-125 is elevated in most advanced cases |
| Germ cell | Adolescents and young women | Dysgerminoma: LDH; yolk sac tumor: AFP; choriocarcinoma: hCG; usually unilateral and highly curable |
| Sex cord–stromal | Any age | Granulosa cell: inhibin, estrogen effects (AUB, endometrial hyperplasia, precocious puberty); Sertoli-Leydig: androgens (virilization) |
Risk and Protection
- Risk: Age, BRCA1 (lifetime ovarian cancer risk about 39%–44%), BRCA2 (about 11%–17%), Lynch syndrome, endometriosis (clear cell and endometrioid types), nulliparity, and infertility.
- Protection: Combined oral contraceptives (roughly 50% risk reduction after about 5 or more years), pregnancy, breastfeeding, tubal sterilization, and especially salpingectomy. Risk-reducing salpingo-oophorectomy is advised for BRCA1 carriers at 35–40 and BRCA2 carriers at 40–45 once childbearing is complete.
Symptoms and Screening
Persistent, new symptoms occurring more than 12 times a month, such as bloating, early satiety, pelvic or abdominal pain, and urinary urgency or frequency, warrant evaluation. The USPSTF recommends against screening average-risk women with CA-125 or ultrasound (grade D) because screening did not reduce mortality and led to harmful surgery.
When to Refer an Adnexal Mass to Gynecologic Oncology (ACOG)
- Postmenopausal: Elevated CA-125, ascites, a nodular or fixed pelvic mass, or evidence of abdominal or distant metastasis.
- Premenopausal: Very elevated CA-125, ascites, or evidence of metastasis.
- Either: A high-risk score on a validated tool (O-RADS, IOTA rules, OVA1, or ROMA) or a strong family history of breast or ovarian cancer.
- Everyone with epithelial ovarian cancer should be offered germline genetic testing.
Cervical Cancer
Cervical cancer is driven by persistent high-risk HPV; HPV types 16 and 18 cause about 70%. Squamous cell carcinoma is most common, followed by adenocarcinoma, which screening detects less well. Most cases occur in women who were never screened or were screened inadequately. Warning signs are postcoital bleeding, intermenstrual bleeding, and watery or bloody discharge. A visible cervical lesion needs biopsy even if recent cytology was normal. Early disease is treated surgically; locally advanced disease is treated with chemoradiation.
Vulvar Cancer
About 90% of vulvar cancers are squamous cell carcinomas, arising by two pathways:
- HPV-associated: Younger women and smokers, preceded by vulvar HSIL (usual-type VIN).
- HPV-independent: Older women, arising from lichen sclerosus through differentiated VIN (dVIN).
Presentation is chronic pruritus, a plaque, an ulcer, or a mass. Biopsy any persistent, changing, pigmented, or nonhealing vulvar lesion, especially in lichen sclerosus that does not respond to clobetasol. Melanoma is the second most common vulvar malignancy.
Vaginal Cancer
Primary vaginal cancer is rare; most vaginal malignancies are metastases from the cervix or endometrium. Primary squamous cell carcinoma is HPV-related and more common after prior cervical neoplasia. Clear cell adenocarcinoma is linked to in utero diethylstilbestrol (DES) exposure, which is why women exposed to DES need careful vaginal as well as cervical examination.
A 61-year-old woman reports 3 months of abdominal bloating, early satiety, and urinary frequency occurring most days. Transvaginal ultrasound shows a 9-cm complex right adnexal mass with solid components and a small amount of ascites. CA-125 is 410 U/mL. What is the most appropriate next step?
Repeat ultrasound and CA-125 in 6–8 weeks to check for resolution.
Prescribe a combined oral contraceptive to suppress a functional cyst.
Refer her to a gynecologic oncologist for surgical evaluation.
Order a colonoscopy and refer to gastroenterology for presumed irritable bowel syndrome.
A 19-year-old presents with a rapidly enlarging, unilateral, solid ovarian mass. Her serum lactate dehydrogenase (LDH) is markedly elevated, while AFP and hCG are normal. Which tumor is most likely?
High-grade serous carcinoma
Dysgerminoma
Mature cystic teratoma
Granulosa cell tumor
A 70-year-old woman treated for lichen sclerosus for many years reports a new, painful, nonhealing area on the left labium majus that has not improved after 6 weeks of clobetasol. Examination shows a 1-cm indurated ulcer within the white sclerotic plaque. What is the most appropriate next step?
Increase clobetasol to three times daily and reassess in 3 months.
Prescribe valacyclovir for presumed recurrent genital herpes.
Apply trichloroacetic acid to the ulcer weekly.
Perform a punch biopsy of the ulcer and its edge.
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