Evolutionary dynamics of ten novel Gamma-PVs: insights from phylogenetic incongruence, recombination and phylodynamic analyses

Abstract Background Human papillomaviruses (HPVs) are genetically diverse, belonging to five distinct genera: Alpha, Beta, Gamma, Mu and Nu. All papillomaviruses have double stranded DNA genomes that are thought to evolve slowly because they co-opt high-fidelity host cellular DNA polymerases for their replication. Despite extensive efforts to catalogue all the HPV species that infect humans, it is likely that many still remain undiscovered. Here we use the sequences of ten novel Gammapapillomaviruses (Gamma-PVs) characterized in previous studies and related HPVs to analyse the evolutionary dynamics of these viruses at the whole genome and individual gene scales. Results We found statistically significant incongruences between the phylogenetic trees of different genes which imply gene-to-gene variation in the evolutionary processes underlying the diversification of Gamma-PVs. We were, however, only able to detect convincing evidence of a single recombination event which, on its own, cannot explain the observed incongruences between gene phylogenies. The divergence times of the last common ancestor (LCA) of the Alpha, Beta, Mu, Nu and Gamma genera was predicted to have existed between 49.7–58.5 million years ago, before splitting into the five main lineages. The LCA of the Gamma-PVs at this time was predicted to have existed between 45.3 and 67.5 million years ago: approximately at the time when the simian and tarsier lineages of the primates diverged. Conclusion Consequently, we report here phylogenetic tree incongruence without strong evidence of recombination

Prevalence of Cutaneous Human Papillomavirus infections at Parirenyatwa hospital's Kaposi Sarcoma Clinic and the Opportunistic Infections Clinic: Association with Non- Melanoma Skin Cancers

Human papillomavirus (HPV) types from the Betapapillomaviruses (ß-HPVs) genus are ubiquitous in non-melanoma skin cancers (NMSC), hyperkeratotic skin warts and in cancer free skin biopsies among fair skinned races. There is paucity of information regarding the prevalence and distribution of ß-HPVs among black Africans. To determine the prevalence of ß-HPV genotypes in cutaneous infections among black Zimbabweans and their association with NMSC, a cross-sectional study was carried out in which skin biopsies were collected from patients attending a referral hospital. HPV typing was done by Primer mix polymerase chain reaction (PM-PCR) and the subsequent reverse hybridization assay (RHA) which is known to identify 25 cutaneous ß-HPV types implicated in skin lesions. We included 144 Black participants with clinically apparent cutaneous warts (n=28), suspected NMSC (n=98) and Kaposi sarcoma (KS) (n=18). The skin biopsies were analyzed for HPV DNA presence and type. The frequency of ß-HPV DNA was 70.1% (101/144). HPV DNA positivity was significantly higher in the HIV infected group 79.2% (57/72) compared to the HIV uninfected 61.1% (44/72), [OR=2.42, 95%CI (1.09-5.47), P=0.018]. All warts patients were HPV DNA positive and 89% (16/18) of those with KS and 58% (57/98) of those with NMSC. Single HPV infections were observed in 33.7% (34/101) of the participants that were HPV DNA positive, 66.3% (67/101) had multiple HPV types and 20.8% (21/101) had greater than five HPV types. The frequency and distribution of different HPV types did not show associations with neither age, sex, biopsy type but showed association with immune status. ß-HPVs are not uncommon in the Zimbabwean black population with skin lesions. There is a difference in the types of HPV genotypes detected in the skin lesions in this population (ß species 1 predominance) when compared to European populations, where there is a ß species 2 predominance. The study provides baseline molecular-epidemiological information for cutaneous HPV infections in Zimbabwe. However, wider national surveys using less invasive techniques are warranted to establish the exact extent of HPV cutaneous infections for more effective public health interventions.,The Letten Foundation of Norway and The ICOHRTA programm

Vaccine and Non-Vaccine HPV Types Presence in Adolescents with Vertically Acquired HIV Five Years Post Gardasil Quadrivalent Vaccination: The ZIMGARD Cohort.

BACKGROUND Human papillomavirus (HPV) vaccination programs are a key intervention in protecting individuals against HPV-related disease. HIV1-infected individuals are at increased risk of HPV-associated cancers. This study was conducted to evaluate the potential role of prophylactic HPV vaccines in preventing new HPV infections among participants with perinatally acquired HIV who received the quadrivalent HPV vaccine at least five years before this study. METHODS This cross-sectional study was conducted at Newlands Clinic, Harare, Zimbabwe. The clinic provided the Gardasil quadrivalent HPV vaccine (4vHPV) to 624 adolescents living with HIV starting in December 2015. Vaginal and penile swabs were collected and tested for HPV types from the study participants who had received the 4vHPV vaccine 5-6 years before enrolment. RESULTS We present the results of 98 participants (44.6% female) vaccinated at a median age of 15 years (IQR 12-16). The mean amount of time since vaccination was 6 years (SD: ±0.4). The HPV-positive rate amongst the analyzed swabs was 69% (68/98). Among 30/98 (31%) HPV-positive participants, 13/98 (13%) had low-risk HPV types, and 17/98 (17%) had high-risk HPV types. Twelve participants tested positive for HPV18, only one participant tested positive for HPV16, and an additional four (4.3%) tested positive for either type 6 or 11, with respect to vaccine-preventable low-risk HPV types. CONCLUSION The Gardasil quadrivalent HPV vaccine (4vHPV) was expected to protect against infection with HPV types 16, 18, 6, and 11. We demonstrated a possible waning of immunity to HPV18 in 17% of the participants, and an associated loss in cross-protection against HPV45. We observed a relatively high prevalence of 'opportunistic non-vaccine HPV types' or 'ecological niche occupiers' in this cohort, and suggest further research on the involvement of these types in cervical and other genital cancers. Our study is one of the few, if not the first, to report on HPV vaccine immunoprotection among people living with HIV (PLWH), thereby setting a baseline for further studies on HPV vaccine effectiveness among PLWH