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Progression to Anal Cancer Precursor
11 Per 100 Person-Years in HIV+ MSM
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18th European AIDS Conference, EACS 2021, October 27-30, 2021, London
Mark Mascolini
Early anal lesions progressed to high-grade squamous intraepithelial lesions (HSIL), a possible prelude to anal cancer, at a rate of 11 per 100 person-years among HIV-positive men who have sex with men (MSM) studied at Bellvitge University Hospital in Barcelona [1]. Almost half of HSIL cleared during the study period.
Human papillomavirus (HPV) infection can lead to squamous intraepithelial lesions, patches of abnormal tissue on a tissue surface [2]. If that abnormality spreads down into lower tissue layers, it can become cancer. In anal tissue, low-grade squamous intraepithelial lesions (LSIL) can evolve into HSIL, which can go on to become anal cancer, But most HSIL does not progress to anal cancer, and sometimes HSIL regresses into a less dangerous lesion or disappears.
People with HIV run a high risk of HSIL and anal cancer. But treating HSIL to prevent anal cancer in HIV-positive people or other high-risk groups has been controversial because HSIL might not develop into anal cancer and may even clear over time without therapy. Just before EACS 2021, a trial involving 4446 people with HIV at 21 US centers stopped because early results showed convincingly that people randomized to HSIL treatment versus close follow-up had significantly reduced chances of progression to anal cancer [3].
The Barcelona study aimed to determine the incidence (new detection rate), clearance, persistence, and predictors of HSIL in MSM with HIV for 2 to 4 years of follow-up. The researchers defined HSIL incidence as a new HSIL diagnosis after a baseline visit without HSIL. HSIL clearance meant no HSIL in two consecutive visits after HSIL diagnosis. And persistent HSIL meant no clearance after 2 or more years of follow-up.
The study involved 354 MSM with HIV in the ELAVI-67 cohort who had 2 to 4 years of follow-up. Participants had an anal smear for anal cytology (cell tests) and viral biomarkers. These men also had high-resolution anoscopy with guided biopsies to areas of dysplasia (anal lesions). Researchers used HPV DNA and E6/E7 mRNA tests to detect high-risk HPV genotypes.
The investigators combined results of cytology and high-resolution anoscopy to divide participants into those with a composite non-HSIL result (who had follow-up every 12 months) and those with a composite HSIL result (who had follow-up every 6 months until lesion clearance).
The study group averaged 45.3 years in age, nadir and current CD4 count averaged 335 and 802, and 87% of men had an undetectable HIV load. While 35% of the group had fewer than 30 lifetime sexual partners, 24% had 30 to 50, 14% had 50 to 100, and 26% had more than 100. More than half of the men, 55.5% practiced receptive anal intercourse, 30% had a history of anogenital warts, 45.5% had a sexually transmitted disease history, and 39% smoked.
At the initial study visit, 90 of 354 MSM (25.4%) had a composite HSIL result. Among 289 men with at least 2 years of follow-up (81.6% of 354), 72 (24.9%) had HSIL at the initial visit and 217 (75.1%) had a non-HSIL result at baseline. Among the 217 men without HSIL at baseline, 62 (28.6%) had incident HSIL during follow-up (incidence 11 per 100 person-years). All told, 103 MSM had HSIL and at least 2 years of follow-up. Among those 103 men, 54 (52.4%) had persistent HSIL during follow-up (incidence 19 per 100 person-years) and 49 (47.6%) had HSIL clearance (incidence 18 per 100 person-years). Overall follow-up averaged 33.7 months.
In the 217 MSM without HSIL at baseline and at least 2 years of follow-up, 7 factors distinguished the 62 men with incident HSIL from the 155 with persistent non-HSIL status: proportion with an undetectable HIV load (77.4% vs 91.6%, P = 0.006), positive HC2 HPV DNA test (48.4% vs 23.3%, P = 0.001), positive LA HPV DNA test for genotypes included in E6/E7 mRNA test (75.8% vs 54.7%, P = 0.027), positive HPV-16 LA HPV DNA test (24.2% vs 11.0%, P = 0.02), positive E6/E7 mRNA test (59.7% vs 30.3%, P < 0.001), positive HPV-16 E6/E7I mRNA test (17.7% vs 4.5%, P = 0.004), and positive HPV-16 and/or HPV-18/-45 E6/E7 mRNA test (24.2% vs 7.1%, P = 0.001).
In the 103 MSM with HSIL and at least 2 years of follow-up, only one variable distinguished the 49 men with HSIL clearance from the 54 with persistent HSIL: positive HC2 HPV DNA test (51.0% vs 75.9%, P = 0.015).
The Barcelona team concluded that progression to HSIL in these HIV-positive men occurred at a rate of 11 per 100 person-years, or 11 new HSIL diagnoses for every 100 people each year. They suggested that the E6/E7 mRNA biomarker could be useful in screening for HSIL. Finding markers linked to clearance of HSIL would help determine which people do not need HSIL treatment.
References
1. Silva-King AC. Natural history of HPV-associated anal lesions in men who have sex with men living with HIV. 18th European AIDS Conference, EACS 2021, October 27-30, 2021, London. Abstract OS2/4.
2. University of California, San Francisco. Anal cancer information. HSIL and LSIL. https://analcancerinfo.ucsf.edu/hsil-and-lsil
3. Fernandez E. Treating anal cancer precursor lesions reduces cancer risk for people with HIV. Groundbreaking national clinical trial halted due to therapy's high success rates. University of California San Francisco. October 8, 2021.
https://www.ucsf.edu/news/2021/10/421591/treating-anal-cancer-precursor-lesions-reduces-cancer-risk-people-hiv
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