Intra-host sequence variability in human papillomavirus

Abstract

Human papillomaviruses (HPVs) co-evolve slowly with the human host and each HPV genotype displays epithelial tropisms. We assessed the evolution of intra HPV genotype variants within samples, and their association to anogenital site, cervical cytology and HIV status. Variability in the L1 gene of 35 HPV genotypes was characterized phylogenetically using maximum likelihood, and portrayed by phenotype. Up to a thousand unique variants were identified within individual samples. In-depth analyses of the most prevalent genotypes, HPV16, HPV18 and HPV52, revealed that the high diversity was dominated by a few abundant variants. This suggests high intra-host mutation rates. Clades of HPV16, HPV18 and HPV52 were associated to anatomical site and HIV co-infection. Particularly, we observed that one HPV16 clade was specific to vaginal cells and one HPV52 clade was specific to anal cells. One major HPV52 clade, present in several samples, was strongly associated with cervical neoplasia. Overall, our data suggest that tissue tropism and HIV immunosuppression are strong shapers of HPV evolution.

The HPV16 Genome Is Stable in Women Who Progress to In Situ or Invasive Cervical Cancer: A Prospective Population-Based Study

“…Potentially even larger intrahost variation has been reported if HIV-positive women are included (22). Limitations of our study thus include restriction by design to the intraindividual longitudinal perspective, restriction to women developing squamous cervical lesions, the limited inference to other ethnic groups than Caucasians, and the small number of controls that precluded more sophisticated analyses by, for example, casecontrol status over time.…”

Recombination Between High-Risk Human Papillomaviruses and Non-Human Primate Papillomaviruses: Evidence of Ancient Host Switching Among Alphapapillomaviruses

“…Traditionally, PVs have been thought to evolve slowly because they replicate by co-opting high-fidelity host cellular DNA polymerases that have an error rate of about 4.3 × 10 − 5 substitutions per nucleotide site per year (Korona et al 2011). The general assumption is that PVs have coevolved with their hosts (Chen et al 2009a;Bravo and Felez-Sanchez 2015;Dube Mandishora et al 2018). Selection pressures due to host immune responses differ among PV genes and result in these genes displaying different substitution rates.…”

High prevalence of human papillomavirus and European variants of HPV 16 infecting concomitantly to cervix and oral cavity in HIV positive women

“…The prevalence of HPV infection in women worldwide is estimated to range from 2-44% [1]. It has been demonstrated that the majority of reproductive-age women who are sexually active have been exposed to one or more types of HPV in the genitals (approximately 50%) and oral cavity (30%) [2].…”

“…Infection with hrHPV could be aggravated by immunosuppression, such as that observed in HIV patients [2]. Developing countries present the highest prevalence of HPV [5] and HIV [6] infections.…”