DURBAN, SOUTH AFRICA – Screening for anal cancer in HIV-infected men or women should not be part of routine clinical practice at this time, Andrew Grulich, MBBS, PhD, declared at the 21st International AIDS Conference.
Some experts recommend anal cytologic screening or high-resolution anoscopy for HIV-positive men and women, but it’s worth noting that strategy hasn’t been incorporated into any national practice guidelines.
Bruce Jancin/Frontline Medical News
Dr. Andrew Grulich
“And for very good reason: When we have a condition with a prevalence that’s so high and a treatment with recurrence rates that are so high, I think we need to question our approach,” said Dr. Grulich, professor of medicine and head of the HIV epidemiology and prevention program at the University of New South Wales in Sydney, Australia.
Screening proponents point to the high incidence of anal cancer in persons with HIV infection. It’s the fourth most common cancer in HIV patients in the United States, behind the AIDS-defining cancers and lung cancer. Indeed, the anal cancer rate is 10-fold greater in HIV-positive women, heterosexual men, and injection drug users than in the HIV-negative general population, and 50-fold higher in HIV-positive gay and bisexual men. Screening proponents also draw an analogy between anal cancer screening and the screening and treatment of cervical intraepithelial neoplasia (CIN), which has been enormously successful in preventing cervical cancer. But Dr. Grulich said he believes the cervical cancer screening analogy is faulty.
Colposcopy has a mean 90% specificity for diagnosis of HPV-related high-grade squamous intraepithelial lesions (HSIL) or cervical cancer, while high-resolution anoscopy as a diagnostic test has a specificity as low as 37% in HIV-positive persons. The prevalence of HSIL is 30%-40% in anal samples from HIV-infected homosexual men, compared with 1%-2% in cervical samples from HIV-negative women.
The rate of progression from CIN-3 to cervical cancer in women in the general population is about 1 in 80 per year. In contrast, the rate of progression from anal intraepithelial neoplasia (AIN)-2 or AIN-3 to anal cancer in HIV-infected homosexual men is estimated at only 1 in 400-600 per year, probably because regression of anal lesions is quite common.
Moreover, while a single treatment of high-grade CIN is typically curative and entails little morbidity, destruction of AIN by means of heat, cold, or electricity has a 70% failure rate, carries substantial morbidity, and is not supported by any evidence that it actually reduces the incidence of anal cancer, he continued.
“We’re in a bit of a quandary regarding what to do about anal cancer prevention. We really need research in order to move this field forward,” Dr. Grulich said.
He added that it’s worth keeping an eye on two ongoing studies addressing key questions surrounding anal cancer in HIV-positive persons. The U.S. National Cancer Institute–funded randomized ANCHOR trial is examining ablative therapy versus watchful waiting in HIV-infected patients with anal HSIL lesions; however, results of this large study aren’t expected until 2022 or 2023. And Dr. Grulich heads the Study of the Prevention of Anal Cancer, aimed at identifying biomarkers that predict persistence of HSIL as a marker of anal cancer risk.
A study he would very much like to see funded is a randomized, placebo-controlled, adequately powered trial of the 9-valent HPV vaccine in HIV-infected gay or bisexual men over age 26. At the 2016 meeting of the Conference on Retroviruses and Opportunistic Infections (CROI), Timothy J. Wilkin, MD, of Cornell University, New York, presented the results of the phase III ACTG A5298 trial of the quadrivalent HPV vaccine in HIV-infected adults over age 26. The vaccine group had a 27% reduction in risk of persistent anal HPV compared with placebo, which wasn’t statistically significant because of the small study size. The 9-valent vaccine would prevent a broader range of oncogenic HPV types.
Dr. Grulich reported receiving research funding from CSL Australia, Gilead Sciences, Viiv, and Hologic.