Women living with HIV had a higher risk of anal pre-cancerous changes than cervical changes linked to human papillomavirus (HPV), French researchers reported at the 14th European AIDS Conference in Brussels. They suggested that all women with HIV ought to be screened routinely for pre-cancerous changes in the anal canal.
The study also found that there was no association between pre-cancerous changes in the anal canal and a prior history of anal intercourse, but a strong association with a previous history of cervical HPV-related disease.
Clinical management guidelines for women with HIV recommend routine screening for pre-cancerous cervical changes according to national guidelines. There is no consensus regarding anal screening in women with HIV.
French researchers carried out a study to determine the prevalence of anal HPV infection and pre-cancerous changes in the anus among women with HIV participating in a national cohort study. The study recruited 319 women who agreed to anal HPV screening, of whom 171 (54% of the cohort) consented to an anal examination by a proctologist. Women who declined to take part in the anal examination had significantly higher CD4 counts, a longer duration of HIV infection and a higher frequency of viral suppression on antiretroviral treatment (98% of all participants were taking antiretroviral therapy) .
The median age of women who took part in the study was 47 years, the median CD4 cell count 655 cells/mm3 and 36% were from sub-Saharan Africa. Thirty-six per cent of the women reported a prior history of receptive anal intercourse.
Women underwent cervical PAP and HPV testing and anal cytology and HPV testing. High-resolution anoscopy was performed in order to identify the stage of any lesions in the anal canal.
Anoscopy diagnosed anal lesions in 34% of women (21 of 171 samples were excluded due to unsatisfactory sampling). Low-grade (AIN-1) lesions were diagnosed in 21% of women and high grade (AIN 2-3) intraepithelial neoplasia in 13% of women. One woman was diagnosed with anal cancer. A high prevalence of HPV types associated with cancer was detected (57%). Two-thirds of women with high-risk HPV sub-types had more than one high-risk sub-type.
The sensitivity of high-resolution anoscopy to detect high-grade anal intraepithelial neoplasia was 76% and the specificity 61%.
By multivariate analysis high-grade anal intraepithelial neoplasia (HGAIN) was associated with a history of cervical low-grade intraepithelial lesions (relative risk 4.0, 95% confidence interval 1.0-15.8, p = 0.05). HGAIN was more strongly associated with the detection of HPV-16 (relative risk 15.6, 95% confidence interval 5.2-46.8, p<0.0001).
In a comparison of cervical and anal cytology and HPV testing results, both low-grade lesions and high-risk HPV types were found to be more common in the anal canal.
This study was cross-sectional in design, and so evaluated only the prevalence of HPV-associated lesions and high-risk HPV types. The tendency of low-grade cervical lesions to regress during follow-up has led to uncertainty regarding the natural history of HPV-related anal lesions, so a prospective study which followed women for several years might lead to different estimates of risk. Nevertheless, the French research group concluded that their findings suggest that anal HPV screening may be warranted in all women with HIV.
High prevalence of pre-cancerous changes in gay and bisexual men with HPV
European AIDS Clinical Society guidelines recommend anal screening by PAP smear for gay and bisexual men with HIV but implementation of this guidance varies according to national screening recommendations and local resources.
A study of systematic anal screening in a cohort of gay and bisexual men attending the St Pierre University Hospital clinic in Brussels found abnormalities by anal cytology in 48% of 382 analysable samples (10% were excluded due to insufficient sampling), of which 19% were classified as ASCUS and 4% as ASC-H. Biopsies were carried for 118 of the 183 patients with abnormal cytology. Thirty-nine per cent of these patients were found to have AIN-2 or 3 (46 out of 383 patients screened), an approximate prevalence of 18%.
The most significant risk factor for AIN 2-3 was a shorter duration of fully suppressed viral load (15 months versus 21 months in those without, p = 0.0158) and a nadir (lowest-ever) CD4 cell count below 100 cells/mm3. In multivariate analysis nadir CD4 count emerged as the stronger predictor of AIN 2-3 (RR 2.8, 95% CI 1.2-6.3, p = 0.014).
Comparing her results with those of other recent studies of AIN prevalence in men who have sex with men, Agnés Libois said that other studies had shown higher prevalence, but that low nadir CD4 count has shown a consistent association with HGAIN and anal cancer across a number of studies. Similarly, a longer duration of viral suppression on treatment has been associated with a lower risk of anal cancer in a number of studies in both men and women, she said. However, the extent to which earlier initiation of treatment might reduce the risk of anal cancer remains to be established, she concluded.
As in women, frequent regression of high-grade lesions has been observed in men who have sex with men.
These studies are unlikely to settle the ongoing debate regarding the cost-effectiveness of anal screening in men or women, but do highlight particular patient sub-groups who might be prioritised for screening.
References
Heard I et al. High prevalence of anal human papilloma virus infection and related cancer precursors in a contemporary cohort of asymptomatic HIV-infected women. 14th European AIDs Conference, Brussels, abstract PS6/4, 2013. View the abstract on the conference website.
Libois A et al. High prevalence of anal dysplasia in a cohort of HIV positive MSM enrolled in a systematic screening program: risk factors and positive impact of CART. 14th European AIDS Conference, Brussels, abstract PS6/3, 2013. View the abstract on the conference website.