CROI 2015: Screening May Miss Pre-cancerous Anal Lesions in Women with HIV

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Existing algorithms to screen for anal cancer in women living with HIV could be missing many cases of anal high-grade squamous intraepithelial lesions (HSIL) -- abnormal tissue changes that may be a precursor to invasive anal cancer -- according to a study reported at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle. 

In addition, even though the likelihood of a diagnosis of anal HSIL (or high-grade anal dysplasia or neoplasia) by anal tissue examination increased with the degree of abnormality found on anal cytology (anal Pap testing), HSIL diagnoses were made even for women who had less severe abnormalities in their anal Pap tests according to Fanny Ita-Nagy of the Mt. Sinai Icahn School of Medicine, who presented the study findings.

The overall incidence of anal cancer in the U.S. is approximately 1.8 per 100,000 person-years and has been increasing. However, HIV infection increases the risk of anal cancer in both men and women. The incidence of anal cancer among women living with HIV is at least 10 times higher than among HIV-negative women, and rates as high as 30 per 100,000 person-years have been reported -- similar to the high incidence of cervical cancer seen before the implementation of cervical cytology screening, or routine Pap tests, in the 1950s.

The vast majority of anal cancer, like cervical cancer, is caused by high-risk strains of human papilloma virus (HPV). Studies have shown that people with HIV are more likely to carry high-risk strains and less likely to clear HPV spontaneously. Further, anal HPV infection and dysplasia (abnormal tissue changes) may be more prevalent or persistent in the anus than in the cervix.

Despite the risk, there is no consensus on the best screening algorithms for anal HSIL in women living with HIV. Currently there are 2 sets of screening guidelines:

However, since 2009, Mt. Sinai Medical Center -- which provides care to over 3000 people living with HIV, 29% of whom are women -- has been offering anal cytology screening to all patients with HIV regardless of previous HPV-associated disease or perceived risk factors. Whenever anyone has abnormal anal cytology, they are referred for high-resolution anoscopy -- which includes biopsy of any abnormal tissue found -- for diagnosis (performed by a single provider).

The resulting data set provided Ita-Nagy and colleagues with an opportunity to assess the prevalence and associated risk factors for anal HSIL in women living with HIV over the 5-year period since the implementation of the screening program.

A total of 877 women with HIV received anal cytology screening. Of these, 484 (55%) were found to have abnormal anal cytology, defined as having atypical squamous cells of undetermined significance (ASCUS) or a higher degree of abnormality. Of the women with abnormal cytology, 290 (60%) subsequently underwent anoscopy. Among these women the mean age was 47 years, the mean CD4 cell count was 572 cells/mm3, and 66% had undetectable HIV viral load. A majority (71%) also had abnormal cervical cytology, 37% had a history of anogenital warts, and 66% reported a history of anal sex; 40% were current smokers, 26% were former smokers, and 33% had never smoked.

Results

o   35% had benign findings -- either a normal anoscopy or benign histology findings;

o   38% had low-grade squamous intraepithelial lesions (LSIL or mild dysplasia);

o   27% had HSIL or high-grade dysplasia on biopsies.

"Screening for anal dysplasia in all HIV-infected women regardless of previous HPV-associated disease or perceived risk factors may be appropriate given the increased risk of anal cancer in this population," concluded Ita-Nagy.

During the following discussion, an audience member suggested that the algorithms might perform better if they included a history of smoking.

A more serious question is whether detection and early treatment of HSIL actually prevents subsequent invasive anal cancer or improves outcomes --particularly because there is a risk of HSIL recurring. One of Ita-Nagy’s colleagues from Mt. Sinai noted that none of the women who had received treatment after high-grade dysplasia was detected in their program had gone on to develop invasive anal cancer, but that the final answer could only come from a randomized clinical trial.

Fortunately, Joel Palefsky of the University of California at San Francisco and colleagues are currently conducting a multicenter study called ANCHORthat will evaluate the effectiveness of immediate treatment and close follow-up of HIV-positive people with HSIL versus deferring treatment and repeating anoscopy every 6 months until progression to cancer is detected.

3/9/15

Reference

MM Galsa, F Ita-Nagy, G Rodriguez Caprio et al. High rate of HSIL on HRA in HIV-positive Women Not Meeting Criteria for Anal Cancer Screening. 2015 Conference on Retroviruses and Opportunistic Infections. Seattle, February 23-24, 2015. Abstract 90.