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Screening for cervical cancer is important for all women with HIV regardless of reproductive status. The incidence of cervical intraepithelial neoplasia (CIN) among women with HIV is 4-5 times higher than in women without HIV and is inversely correlated with CD4+ cell counts.[84-87] The risk of infection with high-risk HPV subtypes (16 and 18) and the development of high-grade CIN increase with increasing immunosuppression.[88-90] The use of ART, however, is associated with regression of cervical dysplasia, which has not been reported in the absence of ART.
In resource-limited countries, the rate of cervical cancer is higher than in developed countries, which is attributed to less widespread screening and a high rate of loss to follow up. Therefore, cervical cancer screenings in these settings follows the screen-and-treat model. During this single visit, a speculum examination is performed to visualize the cervix, followed by an application of 3% to 5% acetic acid to inspect for characteristic acetowhite lesions. Cryosurgery is subsequently performed during that same visit for women with abnormal examinations.
In developed countries where providers and advanced testing modalities are widely available, the Pap test is the primary mode for cervical cancer screening in women with HIV younger than 30 years of age, whereas for women 30 years of age or older, either Pap testing alone or in concert with HPV DNA cotesting is acceptable practice. For women with HIV younger than 30 years of age, screening for cervical cancer by Pap test should commence within 1 year of sexual activity regardless of mode of HIV transmission (eg, perinatal or sexual exposure) but no later than 21 years of age or, if aged 21-29 years, at initial HIV diagnosis. Cotesting for HPV is not recommended for women with HIV younger than 30 years of age. For women with HIV 30 years of age or older, Pap-only screening or cotest screening should commence at the time of diagnosis. Furthermore, in contrast to the general population where cervical cancer screening is discontinued at 65 years of age, screening in women with HIV should continue throughout their lifetimes.
For women younger than 30 years of age and women 30 years of age or older screened by Pap only: Normal Pap test results should be followed with a second test at 6 or 12 months and then every year after. Following 3 consecutive normal results, the interval between Pap tests should be increased to every 3 years. For a Pap test result showing atypical squamous cells of undetermined significance (ASC-US), reflex HPV testing should be done where available. Colposcopy is recommended if positive; if HPV testing is negative or not done, cytology should be repeated in 6-12 months and subsequent abnormal results showing ASC-US or greater should be followed by referral for colposcopy. For Pap results showing low-grade squamous intraepithelial lesion (LSIL) or worse, including atypical squamous cells, cannot rule out a high-grade lesion (ASC-H), atypical glandular cells (AGC), and high-grade squamous intraepithelial lesion (HSIL), immediate referral for colposcopy is recommended regardless of reflex HPV testing.
For women 30 years of age or older screened by Pap and HPV cotesting: For women with both a normal Pap test result and negative HPV test, follow-up screening can be extended to every 3 years. If the Pap test is normal, but the HPV test is positive, cotesting should be repeated in 12 months with subsequent colposcopy recommended if either test is abnormal, unless the initial positive HPV test detects the presence of HPV 16 or 16/18, in which case, immediate colposcopy is recommended.
A summary of colposcopy recommendations based on cervical cytology and HPV DNA results is outlined in Table 2.
Table 2. Referral for Colposcopy According to Pap Alone or Pap/Oncogenic HPV Cotesting
These recommendations are based on evidence that sexually active women younger than 21 years of age may progress to abnormal cytology at a high rate and that a negative HPV test allows for increased screening intervals by predicting prolonged low risk of cancer. Extending the screening interval for women with HIV with normal test results to 3 years brings their recommendations in line with the current recommendation for women without HIV that a Pap test be performed every 3-5 years.
In addition to cervical cancer, HPV infection can also result in anal intraepithelial neoplasia. Studies have indicated increased prevalence and diversity of anal HPV infection in women with HIV compared with women without HIV, providing additional support for routing screening for anal cancer.[ref: Mullins 2013; ref: Kojic 2011; Mallari 2012] Anal Pap tests can be used as preliminary screening to detect anal neoplasia, although poor correlation has been observed between anal cytology and high-resolution anoscopy.[Mallari 2012] Furthermore, abnormal cervical cytology can be associated with the presence of abnormal anal cytology (relative risk: 1.7; P = .024), and the positive predictive value of cervical Pap tests is poor when used to identify women with abnormal anal cytology.[ref: Kojic 2011] Although there is no consensus for routine screening for anal cancer, the current guidelines for the prevention and treatment of opportunistic infections suggest a careful visual inspection of the vaginal, vulvar, and perianal region and digital examination of the anal canal should be performed routinely.[ref: CDC OI] Cytologic screening for women with HIV, followed by high-resolution anoscopy, may be performed in the case of abnormal examination results.[CDC OI]The Advisory Committee on Immunization Practices recommends routine vaccination with the 9-valent HPV vaccine in females and males aged 11-26 years with HIV (may be started at 9 years of age; catch-up vaccination for ages 13-26 years).[15,99] The initial clinical trials demonstrating a 98% efficacy in preventing cervical intraepithelial neoplasia and external genital lesions were conducted in females without HIV and without previous exposure to the specific HPV subtypes. However, early evidence indicated some vaccine efficacy against persistent infection and cervical lesions in individuals with HIV. Furthermore, preliminary data from additional studies suggest that the HPV vaccine is immunogenic and well tolerated in women with HIV.[10-12] Although robust antibody titers were observed in patients with HIV, these studies have not evaluated the overall efficacy of the HPV vaccine in this patient population. Primary care guidelines from the HIV Medicine Association of the Infectious Diseases Society of America and guidelines on the prevention of opportunistic infections in adults and adolescents with HIV from the CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America also recommend HPV vaccine for all individuals 9-26 years of age with HIV.