Cancers of the Cervix, Vulva, and Vagina
Anuja Jhingran, Anthony H. Russell, Michael V. Seiden, Linda R. Duska, Anne Kathryn Goodman, Susanna I. Lee, Subba R. Digumarthy and Arlan F. Fuller, Jr.
Summary of Key Points
Incidence
• An estimated 12,170 new cases of invasive cervical cancer were anticipated in 2012 in the United States, with 4220 deaths projected.
• Seventy-five percent to 80% are squamous cell carcinomas.
• Since the advent of cytologic screening in the 1940s, the incidence of cervical cancer has been decreasing; however, a steady increase in the incidence of preinvasive disease of the cervix has occurred.
Etiology
• Associated risk factors include race, early age at first coitus, multiple sexual partners, multiparity, lower socioeconomic standing, cigarette smoking, history of sexually transmitted diseases, immunosuppression, and oral contraceptive use.
• Strong association with human papillomavirus (HPV).
• HPV serotypes 16, 18, 31, 33, 45, and 56 account for more than 80% of all invasive cervical cancers.
Evaluation and Staging
• Screening for cervical cancer historically has been done with the Papanicolaou (Pap) smear and pelvic examination.
• Testing for DNA of high-risk oncogenic HPV may be used to triage atypical smears and to reduce the frequency of cytologic screening.
• Biopsies should be performed of gross lesions.
• Patients without gross lesions but with abnormal cytology should undergo colposcopy with directed biopsies and endocervical curettage (ECC) or brushing.
• Once a diagnosis of cancer is made, the patient requires a complete history and physical examination, including bimanual and rectovaginal examination, as well as supraclavicular and groin lymph node examination.
• Cervical cancer is staged clinically, not surgically.
• Assignment of stage of disease may be influenced by findings from chest and skeletal radiography, excretory urography (intravenous pyelogram [IVP]), barium enema, cystoscopy, and proctoscopy.
• Results of computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), or other imaging modalities do not influence assignment of International Federation of Obstetrics and Gynecology (FIGO) stage, but may be important in directing therapy.
Primary Therapy
• High-grade dysplasia or carcinoma in situ may be treated with excisional cone biopsy (i.e., cervical conization performed with loop electrosurgical excision procedure [LEEP], or cold-knife).
• Stage Ia1 (microinvasive cervical cancer with depth of invasion 3 mm or less and 7 mm in width or less) without lymphovascular invasion is managed with conservative surgery (i.e., excisional conization or extrafascial hysterectomy).
• Stage Ia2 lesions (invasion of more than 3 mm depth, and lesion up to 7 mm wide) or Ia1 lesions with lymphovascular invasion are managed with modified radical hysterectomy or a radical trachelectomy.
• Stage Ib lesions and stage IIa lesions may be managed with radical hysterectomy or radiation therapy with equivalent probability of cure but different morbidities. Selected surgical patients with adverse risk factors may benefit from adjuvant postoperative radiation or chemoradiation.
• Patients with stages IIb to IVa generally are treated with radiation therapy with concurrent chemotherapy.
1. Chemotherapy in advanced, persistent, or recurrent setting for cervical cancer results in how much improvement in survival?
2. Patient presents with a International Federation of Obstetrics and Gynecology stage IB2 squamous cell carcinoma of the cervix with imaging that is completely negative for regional and metastatic disease. The tumor is 6 cm in size—what is the best way to manage this patient?
B Concurrent chemotherapy and radiation therapy
C Concurrent chemotherapy and radiation therapy followed by hysterectomy
3. What percentage of vulvar carcinomas are human papillomavirus (HPV) positive?
4. What percentage of vaginal carcinomas are primary carcinomas?
1. Answer: C. Chemotherapy is not effective in cervical cancer, and the effectiveness decreases if the patient has had previous chemotherapy and radiation therapy. The four Gynecologic Oncology Group (GOG) phase III trials demonstrate this answer.
2. Answer: B. In 1999, four phase III studies showed that chemoradiation therapy was better than radiation therapy alone, resulting in a National Cancer Institute alert. A meta-analysis following these studies also confirmed that chemoradiation therapy is better than radiation alone. Studies by the GOG also confirmed that the addition of hysterectomy to definitive radiation therapy did not add an extra benefit and may increase toxicity.
3. Answer: A. This is important because vulvar carcinoma is a disease of two groups and two different etiologies that may result in different response rates to radiation therapy. The two groups are the young, who are more predominately HPV positive, and the old, who are predominantly HPV negative.
4. Answer: A. When a patient presents with a vaginal lesion, the physician should work up the lesion to rule out other primary cancers, particular cervix, endometrium or breast. The presence of other cancers will affect how the patient is managed.
