Cervical Cancer

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

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

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

• 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

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