Screening for Cervical Neoplasia
Since HPV dysplasia is far greater among HIV-infected women, screening HIV-infected women for cervical cancer is critical. Cervical cytologic screening permits diagnosis at precursor stages often prior to invasive cervical cancer. Pap testing alone or co-testing with Pap and HPV DNA are both acceptable screening methods in HIV-infected women, though consensus guidelines vary on follow-up screening intervals. If screening with Pap tests alone, the American College of Obstetricians and Gynecologists (ACOG) and the US Preventive Services Task Force recommend that HIV-infected women undergo cervical Pap testing at initial evaluation, 6 months after baseline, and annually, as long as both Pap results are normal.47-48 The CDC and Department of Health and Human Services (DHHS) recently updated follow-up intervals for screening in HIV-infected women. If the results of 3 consecutive Pap smears are normal, the CDC/DHHS recommend that HIV-infected women 30 years and older be followed with Pap smear testing every 3 years throughout life. HIV-infected women who are younger than 30 years old should have Pap smear testing beginning within 1 year of onset of sexual activity but no later than 21 years of age regardless of sexual history.49
Co-testing with HPV DNA and HPV genotypic testing in combination with Pap smear testing may also be done at baseline in women 30 years and older, and is now the preferred screening method in this group.50-51 Co-testing is not recommended in women younger than 30 years old in both HIV-infected and HIV-uninfected women because of high HPV prevalence in this age group. As per the CDC/DHHS guidelines, HIV-infected women who co-test negative for both PAP and HPV test may have their next cervical screening in 3 years (as opposed to 5 years in HIV-uninfected women). HIV-infected women with a normal PAP but positive HPV test for low-risk types on HPV genotype test may be followed with repeat co-testing in 1 year. Those with abnormal cytology or positive HPV testing at 1 year follow-up are recommended to have colposcopy. Women with high-risk HPV 16 or 18 identified on HPV genotype, should also be referred for colposcopy.49 Women with cytologic results showing atypical squamous cells of undetermined significance (ASCUS) and positive HPV testing or higher grade of dysplasia (low-grade or high-grade squamous intraepithelial lesions), should be referred for colposcopy. Women with cytologic results showing ASCUS but without HPV testing available, may also have repeat cervical cytology performed in 6-12 months.52
Because of the high risk of multifocal disease in HIV-infected women, colposcopic examination should include examination of the vagina and vulva as well as the cervix. Initial and follow-up examinations should include a thorough visual inspection of the anus, vulva, and vagina, as well as the cervix to assess for visible signs of warts, intraepithelial neoplasia or invasive cancer. Biopsy or referral is indicated when inspection or palpation identifies lesions suspicious for intraepithelial neoplasia or cancer.
Close up view of warts.
Warts are caused by the human papilloma virus or HPV.
Credit: Science Picture Co/Science Picture Co
Treatment of Cervical Neoplasia
Primary treatment of CIN in HIV-infected women is generally similar to the management in non-infected women. Treatment for CIN 2/3 in the developed world is primarily through excision through loop electrosurgical excision procedure (LEEP) in which a cone of cervical tissue containing the lesion is removed using an electric wire. CIN1/2 in adolescents and young women desiring future fertility is frequently managed conservatively with increased surveillance rather than LEEP. In developing countries where LEEP is not as readily available, ablation through cryotherapy is often used.52 For CIN 2/3, topical 5-fluorouracil (5-FU) (2 gm of 5% cream biweekly), is recommended as adjunctive therapy to excision or ablation procedures.53
HIV-infected women with CIN should be counseled that recurrence is more frequent than in the general population. Recurrence rates have been shown to be as high as 50% at 1 year, and 60% with longer follow-up in some studies.35-36,46, 54-55 ACOG recommends close follow-up with cervical cytology and colposcopy at 6 month intervals over the first year after treatment.47
While studies on the effect of combination antiretroviral therapy (cART) on CIN have yielded conflicting results, recent data suggest that cART may be associated with regression of CIN.56-63 The WIHS Study found a 12.5% per year overall rate of regression of incident CIN post-cART among HIV-infected women receiving cART. Among 312 women, 45% had lesions that regressed to normal cytology with a median time of regression of 2.7 years. Higher rates of regression were observed in women with higher Cd4+ counts and low-grade incident CIN.56
Treatment of invasive cervical cancer is similar in HIV-infected and HIV-uninfected women and should follow National Comprehensive Cancer Network guidelines.64
Anal HPV Infection in HIV-Infected Individuals
While anal cancer incidence is increasing in the general population, it is substantially higher in the HIV-infected population,3-5 with the highest rates among HIV-infected MSM. In the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) study which combined data from 13 cohort studies, HIV-infected MSM experienced the greatest risk for anal cancer with incidence rates >80 higher than in HIV-uninfected individuals (131/100,000 person years). Anal cancer incidence rates were also significantly higher among HIV-infected other men (46/100,000) and women (30/100,000) compared to the general population (2/100,000).65 In a meta-analysis, HIV-infected men had higher prevalence of anal canal HPV of any type (93 vs. 64%), high-risk HPV types (74% vs. 37%), and anal SIL (57% vs 19%) compared to uninfected men. The risk of progression from high-grade SIL to anal cancer among HIV-infected MSM has been estimated to be 1/377 per year.66 In women, where the prevalence of anal HPV is actually higher than the prevalence of cervical HPV, HIV-infected women have a 7-fold higher incidence of anal cancer than HIV-uninfected women.5,22,31 The introduction of cART has not altered the prevalence of anal SIL, and may be associated with an increased incidence of progression to anal cancer due to the longer life expectancy of HIV-infected individuals.65,67-75