Summary Background Oral human papillomavirus (HPV) infection causes a subset of oropharyngeal cancers. These cancers disproportionately affect men, are increasing in incidence, and have no proven ...prevention methods. We aimed to establish the natural history of oral HPV infection in men. Methods To estimate incidence and clearance of HPV infections, men residing in Brazil, Mexico, and the USA who were HIV negative and reported no history of anogenital cancer were recruited into the HPV Infection in Men (HIM) cohort study. A subset of the cohort who provided two or more oral rinse-and-gargle samples with valid HPV results and who completed a minimum of 2 weeks of follow-up were included in this analysis. Oral rinse-and-gargle samples and questionnaire data were obtained every 6 months for up to 4 years. Samples were analysed for the presence of oncogenic and non-oncogenic HPV infections by the linear array method. Findings 1626 men aged 18–73 years and with a median follow-up of 12·7 months (IQR 12·1–14·7) were included in the analysis. During the first 12 months of follow-up, 4·4% (95% CI 3·5–5·6; n=115 incident infections) of men acquired an incident oral HPV infection, 1·7% (1·2–2·5; n=53 incident infections) an oral oncogenic HPV infection, and 0·6% (0·3–1·1; n=18 incident infections) an oral HPV 16 infection. Acquisition of oral oncogenic HPV was significantly associated with smoking and not being married or cohabiting, but was similar across countries, age groups, and reported sexual behaviours. Median duration of infection was 6·9 months (95 % CI 6·2–9·3; n=45 cleared infections) for any HPV, 6·3 months (6·0–9·9; n=18 cleared infections) for oncogenic HPV, and 7·3 months (6·0–not estimable; n=5 cleared infections) for HPV 16. Eight of the 18 incident oral HPV 16 infections persisted for two or more study visits. Interpretation Newly acquired oral oncogenic HPV infections in healthy men were rare and most were cleared within 1 year. Additional studies into the natural history of HPV are needed to inform development of infection-related prevention efforts. Funding US National Cancer Institute, Merck Sharp & Dohme.
Summary Background Human papillomaviruses (HPVs) cause genital warts and cancers in men. The natural history of HPV infection in men is largely unknown, and that information is needed to inform ...prevention strategies. The goal in this study was to estimate incidence and clearance of type-specific genital HPV infection in men, and to assess the associated factors. Methods Men (aged 18–70 years), residing in Brazil, Mexico, and the USA, who were HIV negative and reported no history of cancer were recruited from the general population, universities, and organised health-care systems. They were assessed every 6 months for a median follow-up of 27·5 months (18·0–31·2). Specimens from the coronal sulcus, glans penis, shaft, and scrotum were obtained for the assessment of the status of HPV genotypes. Findings In 1159 men, the incidence of a new genital HPV infection was 38·4 per 1000 person months (95% CI 34·3–43·0). Oncogenic HPV infection was significantly associated with having a high number of lifetime female sexual partners (hazard ratio 2·40, 1·38–4·18, for at least 50 partners vs not more than one partner), and number of male anal-sexual partners (2·57, 1·46–4·49, for at least three male partners vs no recent partners). Median duration of HPV infection was 7·52 months (6·80–8·61) for any HPV and 12·19 months (7·16–18·17) for HPV 16. Clearance of oncogenic HPV infection decreased in men with a high number of lifetime female partners (0·49, 0·31–0·76, for at least 50 female partners vs not more than one partner), and in men in Brazil (0·71, 0·56–0·91) and Mexico (0·73, 0·57–0·94) compared with the USA. Clearance of oncogenic HPV was more rapid with increasing age (1·02, 1·01–1·03). Interpretation The data from this study are useful for the development of realistic cost-effectiveness models for male HPV vaccination internationally. Funding National Cancer Institute.
ICTV Virus Taxonomy Profile: Papillomaviridae Van Doorslaer, Koenraad; Chen, Zigui; Bernard, Hans-Ulrich ...
Journal of general virology,
08/2018, Volume:
99, Issue:
8
Journal Article
Peer reviewed
Open access
The Papillomaviridae is a family of small, non-enveloped viruses with double-stranded DNA genomes of 5 748 to 8 607 bp. Their classification is based on pairwise nucleotide sequence identity across ...the L1 open reading frame. Members of the Papillomaviridae primarily infect mucosal and keratinised epithelia, and have been isolated from fish, reptiles, birds and mammals. Despite a long co-evolutionary history with their hosts, some papillomaviruses are pathogens of their natural host species. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of the Papillomaviridae, which is available at http://www.ictv.global/report/papillomaviridae.
Abstract This review focuses on recent publications of clinical trials of two prophylactic human papillomavirus (HPV) vaccines: Gardasil® (Merck & Co., Inc., Whitehouse Station, NJ USA), a ...quadrivalent vaccine containing L1 virus-like particles (VLPs) of types -6, 11, 16, and 18, and Cervarix™ (GlaxoSmithKline Biologicals, Rixensart, Belgium), a bivalent vaccine containing VLPs of types -16 and 18. In efficacy trials involving young women, both vaccines produced outstanding efficacy against primary and secondary endpoints associated with the vaccine type HPVs and were highly and consistently immunogenic. Both had excellent safety records and, as expected, the most frequent vaccine-related adverse were mild to moderate injection site sequelae. No evidence of waning protection was observed after four years for endpoints examined ranging from incident infection to cervical intraepithelial neoplasia grade 3 associated with the vaccine type HPVs. Gardasil® was also highly efficacious at preventing vaginal/vulvar lesions and genital warts. However, neither vaccine demonstrated therapeutic efficacy against prevalent infections or lesions, regardless of the associated HPV type. Cervarix™ has shown limited cross-protection against infection with specific closely related types while preliminary results of limited cross-protection have been presented for Gardasil® . As expected, more limited efficacy was noted for both vaccines when women with prevalent infection were included or endpoints associated with any HPV type were evaluated. Immunological bridging trials involving adolescent girls and boys were also recently published. For both vaccines, serum VLP antibody levels in girls were non-inferior to those generated in young women and antibody response to Gardasil® was also non-inferior in boys. The results of these studies have led to the approval of Gardasil® and Cervarix™ by national regulatory agencies in a number of countries.
The major steps in cervical carcinogenesis include infection of the metaplastic epithelium of the cervical transformation zone with one or more of the 12–18 carcinogenic types of human papillomavirus ...(HPV) infection, viral persistence, clonal progression of the persistently-infected epithelium to cervical precancer, and invasion. Although these fundamental steps are established, several new epidemiologic studies have shed light on the factors that influence each of these transitions. The importance of the transformation zone in cervical cancer has been extended to other HPV-induced cancers such as anal or tonsillar cancers. Natural history studies show that HPV with normal cervical cytology and cervical intraepithelial neoplasia (CIN) grade 1 behave similarly, with the majority of both showing regression. Although these studies have demonstrated the importance of HPV persistence in the development of precancer CIN-3, the timing from infection to evidence of CIN-3 varies from 1 to 10 years. Whether equivalent lesions diagnosed later differ in their natural history remains unknown. Several factors have been implicated in enhancing persistence and/or progression. However, none are consistently associated with both except age: young women are less likely to show persistence and older women with persistence are more likely to be at risk of invasive cancer. Recent studies have also underscored the importance of the host immune response in clearance of established infections. Finally, data on non-cervical HPV infections, such as penile infections are limited to date compared to cervical infections. Several ongoing cohort studies should give us further insight into male infections in the near future.
Male sexual behavior influences the rates of cervical dysplasia and invasive cervical cancer, as well as male human papillomavirus
(HPV) infection and disease. Unfortunately, little is known ...regarding male HPV type distribution by age and across countries.
In samples combined from the coronal sulcus, glans penis, shaft, and scrotum of 1,160 men from Brazil, Mexico, and the United
States, overall HPV prevalence was 65.2%, with 12.0% oncogenic types only, 20.7% nononcogenic types only, 17.8% both oncogenic
and nononcogenic, and 14.7% unclassified infections. Multiple HPV types were detected in 25.7% of study participants. HPV
prevalence was higher in Brazil (72.3%) than in the United States (61.3%) and Mexico (61.9%). HPV16 (6.5%), HPV51 (5.3%),
and HPV59 (5.3%) were the most commonly detected oncogenic infections, and HPV84 (7.7%), HPV62 (7.3%), and HPV6 (6.6%) were
the most commonly detected nononcogenic infections. Overall HPV prevalence was not associated with age. However, significant
associations with age were observed when specific categories of HPV, nononcogenic, and unclassified HPV infections were considered.
Studies of HPV type distribution among a broad age range of men from multiple countries is needed to fill the information
gap internationally with respect to our knowledge of HPV infection in men. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2036–43)
Oral human papillomavirus type-16 (HPV16) infection is a risk factor for oropharyngeal cancer. We examined oral HPV infection among healthy men.
Oral rinse/gargle specimens and questionnaire data ...were collected from 1,688 healthy men aged 18 to 74 (median = 31 years), from the United States, Mexico, and Brazil. HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59, and noncarcinogenic HPV types were detected using Roche Linear Array.
Oral HPV DNA was detected in 67 of 1,680 (4.0%, 95% CI = 3.1%-5.0%) β-globin-positive specimens; carcinogenic HPVs were detected in 1.3% (95% CI = 0.8%-2.0%; n = 22) and HPV16 was the most commonly detected carcinogenic HPV type (0.6%, 95% CI = 0.2%-1.1%; n = 10). The prevalence of oral HPV infection was similar by country except for HPV55, which had notably higher prevalence in Mexico (3.0%) than Brazil (0%) or the United States (0.2%). Oral HPV prevalence nonsignificantly increased over increasing age categories (P(trend) = 0.096). The strongest predictor of oral HPV was current tobacco use, which increased the odds 2.5-fold (95% CI = 1.4-4.4). Oral sexual behaviors were not associated with oral HPV infection.
Oral HPV16 infection was rare in healthy men, especially at younger ages, and was positively associated with current tobacco use.
Oral HPV appears to be about 10-fold less prevalent than infection at genital sites in men (4% vs. ∼40%, respectively). It remains unclear whether this reflects reduced exposure or if the oral region is more resistant to HPV infection compared with anogenital sites.
Objectives To estimate the seroprevalence of Chlamydia trachomatis (CT), herpes simplex type-2 (HSV2), hepatitis C (HCV), Epstein-Barr virus (EBV) and nine human papilloma virus (HPV) types, and ...investigated factors associated with the seropositivity among men from three countries (Brazil, Mexico and U.S). Methods Archived serum specimens collected at enrollment for n = 600 men were tested for antibodies against CT, HSV2, HCV, EBV, and 9-valent HPV vaccine types (6/11/16/18/31/33/45/52/58) using multiplex serologic assays. Socio-demographic, lifestyle and sexual behavior data at enrollment were collected through a questionnaire. Results Overall, 39.3% of the men were seropositive for CT, 25.4% for HSV2, 1.3% for HCV, 97.3% for EBV, 14.0% for at least one of the seven oncogenic HPV (types: 16/18/31/33/45/52/58), and 17.4% for HPV 6/11. In the unadjusted models, age, race, smoking, sexual behavior variables, and seropositivity for high-risk HPV were significantly associated with the seropositivity for CT. In multivariable analyses, self-reported black race, higher numbers of lifetime female/male sexual partners, current smoking, and seropositivity to high-risk HPV were significantly associated with increased odds of CT seropositivity. Odds of HSV2 seroprevalence were elevated among older men and those seropositive for high risk HPV. Conclusion Exposure to STIs is common among men. Prevention and screening programs should target high-risk groups to reduce the disease burden among men, and to interrupt the disease transmission to sexual partners.
The high prevalence of human papillomavirus (HPV), the most common sexually transmitted infection, arises from the coexistence of over 200 genetically distinct types. Accurately predicting the impact ...of vaccines that target multiple types requires understanding the factors that determine HPV diversity. The diversity of many pathogens is driven by type-specific or “homologous” immunity, which promotes the spread of variants to which hosts have little immunity. To test for homologous immunity and to identify mechanisms determining HPV transmission, we fitted nonlinear mechanistic models to longitudinal data on genital infections in unvaccinated men. Our results provide no evidence for homologous immunity, instead showing that infection with one HPV type strongly increases the risk of infection with that type for years afterward. For HPV16, the type responsible for most HPV-related cancers, an initial infection increases the 1-year probability of reinfection by 20-fold, and the probability of reinfection remains 14-fold higher 2 years later. This increased risk occurs in both sexually active and celibate men, suggesting that it arises from autoinoculation, episodic reactivation of latent virus, or both. Overall, our results suggest that high HPV prevalence and diversity can be explained by a combination of a lack of homologous immunity, frequent reinfections, weak competition between types, and variation in type fitness between host subpopulations. Because of the high risk of reinfection, vaccinating boys who have not yet been exposed may be crucial to reduce prevalence, but our results suggest that there may also be large benefits to vaccinating previously infected individuals.
The role of inflammation in human papillomavirus (HPV) infection and disease is complex since it involves responses capable of preventing initial infections, clearing those ongoing as well as ...promoting persistence and progression of associated lesions. Avoiding the immune response has been considered a key aspect of HPV persistence which is the main factor leading to HPV-related neoplasia. HPVs have evolved different ways of targeting immune signaling pathways. Moreover, host inflammatory response may promote lesion progression and affect tumor fate by diverse mechanisms including the direct participation of inflammatory cells. In this review, we discuss the interplay between HPV oncogenic proteins and an array of inflammatory responses that ultimately may lead to cancer.
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