{
  "abstract": "Background People living with HIV experience a markedly increased risk of HPV-related malignancies despite effective antiretroviral therapy. Persistent HPV16 infection represents the main driver of anal and oropharyngeal cancers in this population; however, the contribution of viral genetic variability to infection persistence and lesion development remains poorly understood. The HPV16 E6 and E7 oncoproteins play a central role in carcinogenesis by disrupting p53- and retinoblastoma-mediated cell cycle control, promoting cellular immortalization and malignant transformation. Variability within these oncogenes may influence viral persistence and oncogenic potential, particularly in immunologically vulnerable populations. We investigated HPV16 E6 and E7 variability in anal and oral infections among people living with HIV to explore potential associations with lesion grade, anatomical site, and immune status.Material and Methods Anal swabs and oral rinse samples were collected from 53 men who have sex with men living with HIV and receiving antiretroviral therapy. HPV genotyping was performed using real-time PCR, and HPV16-positive samples underwent targeted sequencing of E6 and E7 regions followed by phylogenetic analysis. Cytological findings included high-grade (HSIL), low-grade (LSIL), and negative for intraepithelial lesion or malignancy (NILM). Associations between viral variants, CD4+ T-cell counts, HIV RNA levels, and lesion grade were evaluated.Results A total of 51 E6 and 52 E7 sequences were obtained from persistent HPV16 infections. Most participants showed controlled HIV infection with median CD4+ counts of 681 cells/µL. HPV16 lineage A predominated (96.1%), mainly sublineages A1 (84.3%) and A2 (9.8%). The E6 region showed greater variability than E7, with the L83V substitution detected in 62.7% of cases across all cytological categories and anatomical sites. E7 sequences were highly conserved, with only one non-synonymous mutation identified. No site-specific variants were observed between anal and oral infections. Importantly, viral genetic variability was not associated with lesion severity, CD4+ T-cell count, or HIV viral suppression.Conclusions In people living with HIV receiving effective antiretroviral therapy, persistent HPV16 infection occurs independently of immune recovery and is characterized by highly conserved oncogenic regions across anatomical sites. These findings support the hypothesis that HPV persistence and cancer risk in this population may not depend on specific viral variants but rather on host-virus interactions, reinforcing the need for integrated HPV surveillance and cancer prevention strategies in HIV care.",
  "authors": [
    {
      "affiliations": [
        "Laboratory of Virology, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy"
      ],
      "name": "S Pauciullo"
    },
    {
      "affiliations": [
        "Laboratory of Virology, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy"
      ],
      "name": "V Zulian"
    },
    {
      "affiliations": [
        "Laboratory of Virology, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy"
      ],
      "name": "R Sciamanna"
    },
    {
      "affiliations": [
        "Laboratory of Virology, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy"
      ],
      "name": "A Coppola"
    },
    {
      "affiliations": [
        "Laboratory of Virology, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy"
      ],
      "name": "M De Sanctis"
    },
    {
      "affiliations": [
        "Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, Rome, Italy"
      ],
      "name": "A Borsellino"
    },
    {
      "affiliations": [
        "Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, Rome, Italy"
      ],
      "name": "P Del Porto"
    },
    {
      "affiliations": [
        "Pathology Unit, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy"
      ],
      "name": "F Del Nonno"
    },
    {
      "affiliations": [
        "Pathology Unit, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy"
      ],
      "name": "D Colombo"
    },
    {
      "affiliations": [
        "Clinical and Research Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy"
      ],
      "name": "A Scarabello"
    },
    {
      "affiliations": [
        "Laboratory of Virology, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy"
      ],
      "name": "AR Garbuglia"
    }
  ],
  "title": "SC10 Persistent HPV16 infection despite immune recovery in people living with HIV: analysis of E6 and E7 genetic variability",
  "uid": "bbddd30c-e4b1-5105-9c64-c0fda928f4d8"
}