7.3 Cervical, Uterine & Ovarian Neoplasms

Cervical Cancer and Neoplasia

Cervical cancer is largely a preventable malignancy thanks to widespread cytological screening and HPV vaccination programs. More than 95% of cases are caused by persistent infection with high-risk strains of Human Papillomavirus (hrHPV), most notably types 16 (highest oncogenic potential) and 18. The virus infects the squamocolumnar junction (transformation zone) of the cervix, driving cellular alterations that manifest as cervical intraepithelial neoplasia (CIN) which, if left untreated over years, can progress to invasive squamous cell carcinoma or adenocarcinoma.

Screening Guidelines (General Average-Risk Population):

• Age <21: Screening is not recommended regardless of the age of sexual activity onset. HPV infections are transient and rapidly cleared by the immune system in this cohort.
• Age 21-29: Cytology (Pap smear) alone every 3 years. Routine HPV testing is not recommended due to the high prevalence of transient infections.
• Age 30-65: Three acceptable strategies exist: Primary hrHPV testing every 5 years (preferred in many jurisdictions), co-testing (hrHPV + Pap) every 5 years, OR Pap smear alone every 3 years.
• Age >65: Discontinue screening if there is an adequate negative prior screening history (e.g., 3 consecutive negative Pap tests or 2 consecutive negative co-tests within the past 10 years, with the most recent test within the last 5 years) and no history of CIN 2 or higher.

Management of Abnormal Screening: Colposcopy with directed biopsy is the standard diagnostic step for evaluating significant cervical abnormalities.

• CIN 1 (Low-grade): Generally reflects active HPV infection and often regresses spontaneously; managed with careful observation.
• CIN 2/3 (High-grade): Represents true pre-cancerous dysplasia and typically requires treatment via excisional procedures like the Loop Electrosurgical Excision Procedure (LEEP) or cold knife conization (CKC) to prevent progression to invasive cancer.

Clinical Presentation and Staging: Early-stage cervical cancer is frequently asymptomatic. Advanced disease presents clinically with abnormal vaginal bleeding (classically postcoital spotting), chronic pelvic pain, or a malodorous vaginal discharge.

Endometrial Hyperplasia and Cancer

Endometrial cancer is the most common gynecologic malignancy in developed nations. The overwhelming cardinal symptom is abnormal uterine bleeding. In a postmenopausal woman, vaginal bleeding must be considered endometrial cancer until proven otherwise.

Pathogenesis Types:

1. Type I (Endometrioid): Accounts for 80% of cases. It is estrogen-dependent and develops from a precursor lesion (endometrial hyperplasia).
   • Risk Factors: Conditions characterized by prolonged exposure to unopposed estrogen, including obesity (due to peripheral aromatization of androstenedione to estrone in adipose tissue), nulliparity, early menarche, late menopause, chronic anovulation (e.g., PCOS), estrogen-only hormone replacement therapy, and the use of Tamoxifen (an estrogen agonist in the uterus).
   • Protective Factors: Combined oral contraceptives and multiparity.
2. Type II (Serous/Clear Cell): Accounts for 10-20% of cases. It is estrogen-independent and typically develops from an atrophic endometrium in older women. It is highly aggressive and often presents with extrauterine spread at the time of diagnosis.

Diagnosis:

• Transvaginal Ultrasound (TVUS): Often used as an initial triage tool in postmenopausal women. An endometrial stripe thickness of ≤4 mm confers an extremely low risk of malignancy (<1%), allowing for observation.
• Endometrial Biopsy (EMB): The gold standard outpatient diagnostic test for obtaining tissue pathology.

Management:

• Hyperplasia without atypia: Typically managed medically with progestin therapy (e.g., LNG-IUD or oral medroxyprogesterone) to induce stromal decidualization and glandular atrophy.
• Hyperplasia with atypia or Carcinoma: The definitive primary treatment is surgical staging, which includes a total extrafascial hysterectomy with bilateral salpingo-oophorectomy (TH-BSO) and pelvic/para-aortic lymph node assessment. Postoperative adjuvant therapy (radiation or chemotherapy) is tailored based on surgical staging and final tumor grade.

Ovarian Cancer

Ovarian cancer carries the highest mortality rate among all gynecologic cancers. This high lethality is primarily due to the lack of an effective screening modality and the vague, non-specific nature of early symptoms, leading to late-stage presentation. The vast majority of ovarian cancers are epithelial tumors, with high-grade serous carcinoma being the most prevalent.

Risk Factors: Factors that increase incessant ovulation contribute to risk, including nulliparity, early menarche, and late menopause. Genetic mutations strongly predispose individuals to the disease, particularly BRCA1 and BRCA2 mutations (which impair homologous recombination DNA repair) and Lynch syndrome (HNPCC). Notably, the use of oral contraceptives significantly and durably reduces the risk of ovarian cancer.

Clinical Presentation: Symptoms are notoriously vague: progressive abdominal bloating, early satiety, unexplained dyspepsia, changes in bowel habits, and vague pelvic or abdominal pain. In advanced stages, patients classically present with massive ascites, a palpable complex pelvic mass, and widespread peritoneal carcinomatosis.

Diagnosis & Workup:

• Pelvic ultrasound evaluating for complex adnexal masses (features of concern include solid components, thick septations, papillary projections, and increased vascular flow on Doppler).
• Tumor markers: CA-125 is elevated in approximately 80% of advanced epithelial ovarian cancers. While highly useful for monitoring treatment response and detecting recurrence, it lacks sufficient sensitivity and specificity for general population screening.
• Definitive diagnosis requires comprehensive surgical exploration and staging; image-guided percutaneous biopsy is generally contraindicated if early-stage disease is suspected, as it risks tumor seeding or capsular rupture, which upstages the cancer.

Management: The cornerstone of treatment is aggressive cytoreductive (debulking) surgery, aiming for optimal resection (leaving <1 cm of visible residual disease). This is invariably followed by platinum-based systemic chemotherapy (e.g., carboplatin combined with paclitaxel). For patients with BRCA mutations, PARP inhibitors (e.g., olaparib) are utilized as targeted maintenance therapy with significant efficacy.

Gestational Trophoblastic Disease (GTD)

GTD encompasses a diverse spectrum of proliferative abnormalities of placental trophoblastic tissue. It ranges from benign hydatidiform moles (complete or partial) to highly malignant entities like choriocarcinoma.

• Complete Mole: Karyotype is typically 46,XX (or rarely 46,XY) of entirely paternal origin (an empty ovum fertilized by sperm). No fetal tissue is present. Clinically presents with markedly elevated β-hCG, a uterus larger than expected for gestational age, severe hyperemesis gravidarum, and potentially early-onset preeclampsia. Pelvic ultrasound reveals a characteristic "snowstorm" or vesicular pattern.
• Partial Mole: Karyotype is usually triploid (69,XXX, XXY, or XYY) resulting from a normal ovum fertilized by two sperm. Contains fetal parts and focal trophoblastic hyperplasia.

Management: Suction dilatation and curettage (D&C) is the standard definitive treatment. Post-evacuation, it is critical to perform serial, weekly β-hCG quantitative measurements until levels reach zero, followed by monthly monitoring for 6 months. This rigorous surveillance is to promptly detect progression to Gestational Trophoblastic Neoplasia (GTN, including choriocarcinoma). Reliable contraception must be strictly employed during this entire monitoring period to avoid confounding β-hCG interpretations.