The utility of HPV16 E6 as a potential biomarker for HPV-related cancers in HIV-infected men who have sex with men.

person Naokatsu Ando National Center for Global Health and Medicine, Tokyo, Japan info_outline Naokatsu Ando, Daisuke Mizushima, Haru Hoshino, Misao Takano, Takahiro Aoki, Koji Watanabe, Takato Nakamoto, Akira Kawashima, Seitaro Abe, Birgitta E Michels, Tim Waterboer, Hiroyuki Gatanaga

Authors person Naokatsu Ando National Center for Global Health and Medicine, Tokyo, Japan info_outline Naokatsu Ando, Daisuke Mizushima, Haru Hoshino, Misao Takano, Takahiro Aoki, Koji Watanabe, Takato Nakamoto, Akira Kawashima, Seitaro Abe, Birgitta E Michels, Tim Waterboer, Hiroyuki Gatanaga Organizations National Center for Global Health and Medicine, Tokyo, Japan, German Cancer Research Center, Heidelberg, Germany Abstract Disclosures Research Funding National Center for Global Health and Medicine Background: The burden of HPV-related cancers, including oropharyngeal and anal cancers, poses a significant challenge. Although recent advancements in screening for anal cancer have been made for HIV-infected men who have sex with men (HIV-MSM), establishing effective screening protocols for oropharyngeal cancer remains ongoing. The early oncoprotein HPV16 E6 presents as a promising biomarker for the detection of HPV-associated cancers in this population as well. We investigated the utility of HPV16 E6 in HIV-MSM. Methods: We conducted a retrospective study using an HIV cohort at the AIDS Clinical Center of the National Center for Global Health and Medicine. Participants were all HIV-MSM and included those with HPV-related cancers or precancerous lesions such as oropharyngeal cancer, anal cancer, anal high-grade squamous intraepithelial lesions (aHSIL), and anal low-grade squamous intraepithelial lesions (aLSIL). All cancers and precancerous lesions were histologically confirmed. Frozen plasma samples taken at the time of diagnosis were evaluated. Additionally, when available, samples were retrospectively analyzed up to four years pre- and post-diagnosis. These specimens were sent to the German Cancer Research Center (DKFZ, Heidelberg, Germany) for analysis of antibodies against the early oncoproteins of carcinogenic mucosal HPV types, particularly HPV16 and other high-risk HPVs. Results: One hundred thirty-seven patients living with HIV (PWH) were included in the analysis. The distribution of PWH diagnosed with oropharyngeal cancer, anal cancer, aHSIL, and aLSIL was 6, 14, 96, and 9 respectively. Regarding HPV16 E6 seropositivity, 100% of patients with oropharyngeal cancer tested positive (6/6). Seropositivity rates for anal cancer, aHSIL, and aLSIL were 28.6% (4/14), 12.5% (12/96), and 11.1% (1/9) respectively (Table). Patients with oropharyngeal cancer exhibited the highest titer of HPV16 E6. Among the six patients with oropharyngeal cancer, one demonstrated persistent positivity from four years prior, and four showed positivity from one year prior. Two patients were not assessed as they were newly diagnosed at the time of the study. After chemoradiation treatment, their titers decreased but did not fall below the cutoff level during the follow-up period. In two cases of relapse, the titers, which had initially decreased with chemoradiation, increased again at least one year before the relapse diagnosis. Conclusions: The study demonstrated that screening for HPV16 E6 seropositivity is highly effective for the detection of oropharyngeal cancer in HIV-MSM. This could potentially contribute to early diagnosis and treatment of HPV-related cancers. Oropharyngeal Cancer Anal Cancer HSIL LSIL E6-HPV16, %(N) 100 (6/6) 28.6 (4/14) 12.5 (12/96) 11.1 (1/9) Titer (Interquartile range) 6258(4002-9810.5) 236 (94-2104) 173 (100-277) 217 (107-306)