Cervical carcinoma in the setting of HIV infection has been recognized as an AIDS-defining malignancy since 1993. Unfortunately, in some women, cervical carcinoma may be the first indication that they have HIV infection.
Cervical intraepithelial neoplasia (CIN) is also seen in association with HIV infection. These premalignant lesions, also known as squamous intraepithelial lesions (SILs), may foretell a higher incidence of cervical carcinoma among HIV-infected women. SILs have been associated with human papillomavirus (HPV), particularly those subtypes with greater oncogenic potential, such as serotypes 16, 18, 31, 33, and 35.
Prevalence of HIV infection and cervical abnormalities
The risk of HIV infection in women with an abnormal Pap smear varies with the prevalence of HIV infection in the given population. Screening in clinics in high-prevalence areas has yielded HIV-positivity rates of between 6% and 7% (and up to 10% in parts of Africa). In such high-prevalence areas, among women younger than 50 years with cervical carcinoma, up to 19% were found to be HIV-positive. HIV-positive women have up to a 10-fold increased risk of abnormal cervical cytology. Several centers have reported abnormal cytology rates of 30% to 60% in HIV-positive women and Pap smears consistent with cervical dysplasia in 15% to 40%. The prevalence of cervical dysplasia increases with declining CD4 cell counts in HIV-infected women.
Nationwide, invasive cervical carcinoma was found in 1.3% of women with AIDS. In New York, invasive cervical carcinoma constitutes 4% of AIDS-defining illnesses in women. Recent findings from linkage studies in the United States and Italy clearly have shown increased rates of cervical cancer in women with HIV infection.
Race and geography
The prevalence of invasive cervical carcinoma among American Hispanic and black women is higher than that in white women. However, this difference may stem from a difference in access to health care. The southern and northeastern sections of the United States have a higher reported number of cases of HIV-associated invasive cervical carcinoma.
The severe cellular immunodeficiency associated with advanced HIV infection may allow oncogenic viruses to flourish and may also compromise the body's immunologic defenses that control the development of these tumors.
There is abundant evidence that HPV infection is related to malignant and premalignant neoplasia in the lower genital tract. HPV serotypes 16, 18, 31, 33, and 35 are the most oncogenic strains and have been associated with invasive cervical carcinoma and progressive dysplasia. The prevalence of cervical SILs among HIV-infected women may be as high as 20% to 30%, with many having higher cytologic and histologic grade lesions.
The majority of cervical SILs are detected on routine cytologic evaluation of Pap smears in women with HIV infection.
Advanced invasive disease
Postcoital bleeding with serosanguineous and/or foul-smelling vaginal discharge is usually the first symptom of more advanced invasive disease. Lumbosacral pain or urinary obstructive symptoms may indicate advanced disease.
Because the majority of patients with cervical dysplasia or early invasive cancer are asymptomatic, frequent cytologic screening of women at risk for HIV infection must be undertaken. The role of newly developed HPV vaccines in preventing HPV infection or disease progression in HIV-infected women has yet to be determined.
Screening of HIV-positive women
Current screening recommendations call for women with HIV infection to have pelvic examinations and cytologic screening every 6 months during the first year after HIV diagnosis and then annually if the test results are normal. Pap smears indicating cervical SILs must be taken seriously, and abnormalities justify immediate colposcopy. Although abnormalities are sometimes missed by relying solely on cytologic screening, recommendations for routine colposcopy have not yet been established.
Screening of women with a history of cervical SILs
For women who have a history of cervical SILs, more frequent reevaluation and cytologic screening should be undertaken. Since these women are at high risk for recurrence or development of lesions in other areas of the lower genital tract, post-therapy surveillance with repeated colposcopy also is warranted.
Workup of women with invasive carcinoma
For women with invasive carcinoma, complete staging should be undertaken; this should include pelvic examination, CT of the pelvis and abdomen, chest radiography, and screening laboratory tests for hepatic and bone disease. In addition, full evaluation for and treatment of HIV infection and related complications should be initiated.
Squamous cell carcinoma
Most cases of cervical carcinoma are of the squamous cell type.
The staging classification for cervical carcinoma (see "Cervical Cancer" chapter), as adopted by the International Federation of Gynecology and Obstetrics, also applies to AIDS patients.
Cervical dysplasia in HIV-infected women is often of higher cytologic and histologic grade. These women are more likely to have CIN II–III lesions with extensive cervical involvement, multisite (vagina, vulva, and anus) involvement, and endocervical lesions.
HIV-infected women with cervical carcinoma typically present with more advanced disease and appear to have a more aggressive clinical course. Tumors are typically high-grade with a higher proportion of lymph node and visceral involvement at presentation. Mean time to recurrence after primary treatment is short, and many patients have persistent disease after primary therapy. The median time to death in one series was 10 months in HIV-infected women, compared with 23 months in HIV-negative patients.
Treatment of preinvasive disease
Cryotherapy, laser therapy, cone biopsy, and loop electrosurgical excision procedure have all been used to treat preinvasive disease in HIV-infected patients. Short-term recurrence rates of 40% to 60% have been reported.
Determinants of recurrence. Immune status of the patient seems to be the most important determining factor for recurrence. Close surveillance after initial therapy is critical, and repetitive treatment may be necessary to prevent progression to more invasive disease.
Treatment of cervical carcinoma
The same principles that guide oncologic management of the immunocompetent patient with cervical carcinoma (see "Cervical Cancer" chapter) are used in AIDS patients with this cancer.
Resection. Resection can be undertaken for the usual indications, and surgical decisions should be based on oncologic appropriateness and not on HIV status.
Radiation therapy. Because most AIDS patients with cervical cancer present with advanced disease, radiation therapy is indicated more often than surgery. If the patient's overall physical condition permits, treatment regimens are identical to those used for the same stage disease in uninfected individuals (see "Cervical Cancer" chapter). It is important to note that the standard of care for advanced carcinoma of the cervix (stages III–IV, without hematogenous dissemination) now includes a combination of irradiation and concurrent cisplatin(Drug information on cisplatin)-based chemotherapy. At present, there is insufficient evidence to suggest that irradiation or other treatments for cervical carcinoma in AIDS patients is any less effective than in similar non–HIV-infected individuals.
Chemotherapy. Antineoplastic regimens, such as cisplatin (50 mg/m2) or carboplatin(Drug information on carboplatin) (200 mg/m2), bleomycin(Drug information on bleomycin) (20 U/m2; maximum, 30 U), and vincristine (1 mg/m2), have been used in patients with metastatic or recurrent disease. Vigorous management of side effects and complications of these treatments and of AIDS itself must be provided.