Investigation of three oncogenic epitheliotropic viruses shows human papillomavirus in association with non-melanoma skin cancer.

Non-melanoma skin cancers (NMSC) share similar risk factors with other virus-related cancers, despite the lack of proved causal association between viral infection and NMSC development. We investigated the presence of Merkel cell polyomavirus (MCPyV), Epstein-Barr virus (EBV), and human papillomavirus (HPV) DNA in 83 NMSC fresh-frozen and 16 non-cancerous skin biopsies and evaluated viral infection according to demographical data, histopathological diagnosis, and ultraviolet exposure. Our results showed that 75% of NMSC biopsies were positive for at least one out of three viruses, whereas only 38% of non-cancerous skin biopsies were positive (p = 0.02). Notably, HPV detection was frequent in NMSC (43%) and nearly absent (one sample, 6.7%) in non-cancerous biopsies (p = 0.007). MCPyV was associated with sites of higher exposure to ultraviolet radiation (p = 0.010), while EBV was associated with a compromised immune system (p = 0.032). Our study showed that HPV was strongly associated with NMSC while EBV and MCPyV with other risk factors. Though further studies are required to elucidate the role of viral infection in NMSC development and management, this study supports the possible role of oncogenic viruses in skin cancers, especially HPV.

Human papillomavirus, Epstein-Barr virus, and methylation status of p16ink4a in penile cancer.

Little is known about penile carcinogenesis. The aim of this study was to evaluate the prevalence of HPV and EBV, and the methylation status of p16ink4a in penile cancer samples, and to contribute to the understanding of the mechanisms responsible for penile cancer development. HPV DNA was detected in 63.6% of 122 cases, with HPV16 being the most prevalent type. EBV DNA was detected in 47.7%, with EBV-1 being the most prevalent type. HPV/EBV co-infections were found in 27.3% of the cases. Hypermethylation in p16ink4a was detected in 64.5% of 110 tested cases. An association between the absence of HPV absence and p16ink4a hypermethylation was also found. Death and/or progressive disease was associated with grade (P = 0.001), T stage (P < 0.0001), and N stage (P < 0.0001). In the multivariable model, grade and N stage were independent risk factors for disease-free survival (P = 0.008 and P < 0.001, respectively). Patients without viral infection had a median age significantly lower than that of the HPV-infected patients. We suggest at least two pathways for penile carcinogenesis, one HPV-independent linked to epigenetic events, probably via p16ink4a inactivation; and another, dependent on HPV infection.

The Role of Oncogenic DNA Viruses in Penile Cancer Development.

Penile cancer is a relatively rare neoplasia in developed countries, with significant morbidity and mortality in developing countries. Penile cancer can be subdivided into human papillomavirus (HPV)-positive and HPV-negative cases. Worldwide, the HPV prevalence in penile cancer samples is around 50%, and HPV16 is the most prevalent genotype. Although HPV is an important factor for cancer development, other oncogenic factors may be associated with carcinogenesis. Some of these factors can be infectious, such as the Epstein-Barr virus (EBV), as well as the Merkel cell polyomavirus (MCPyV). The prevalence rates of nearly 50% for both HPV and EBV infections indicate an important role of these viruses in penile tissue malignancy, reinforcing the idea of a multifactorial etiology of the disease. Although the HPV role is better understood, EBV is thought to facilitate persistence, integration, and mutations. Recent studies on the Merkel cell polyomavirus have not shown a relevant prevalence in penile cancer samples, but its presence indicates the opportunistic infectious potential of this virus. Regarding HPV-negative cases, the literature suggests a link with younger age and epigenetic alterations, mainly through the p16INK4a pathway. Recently, several biomarkers that might act as prognostic tools (e.g., Ki-67, squamous cell carcinoma antigen, among others) have been proposed, but the results remain controversial. In addition, other risk factors have also been associated with penile carcinogenesis, such as the presence of phimosis, noncircumcision, chronic inflammation, and number of sexual partners. Further studies are needed to develop tools for early detection and epidemiological surveillance of penile cancer.

Epidemiological surveillance of Human Papillomavirus (HPV) genotypes in oral and genital tracts and the impact of HPV vaccination on male university students from Rio de Janeiro state, Brazil / Vigilância Epidemiológica dos genótipos de papilomavírus humano (HPV) nos tratos oral e genital e o impacto da vacinação em estudantes universitários do sexo masculino do estado do Rio de Janeiro, Brasil

Introduction: Human Papillomavirus (HPV) infections are of significant concern in men, given its potential impact on their health and the risk of transmission to partners. Understanding and addressing this infection in men is crucial to evaluate the effectiveness of vaccination in reducing HPV-related diseases. Objective: To assess the impact of HPV vaccination, potential genotype shifts, and adverse effects, through a prospective study conducted with male university students. Methods:The study involved 286 volunteers who were examined at Sexually Transmitted Disease Clinics at the Universidade Federal Fluminense in Niterói, Rio de Janeiro, Brazil. The HPV prevalence was evaluated using generic PCR, genotyped by DNA microarray and monitored adverse effects. Results: The findings of this study revealed the absence of moderate or severe adverse effects. Genetic shifts were observed, including the disappearance of oncogenic HPV types 16 and 18. Surprisingly, even after completing the full vaccine regimen, students still harbored HPV11 in the oral tract. Furthermore, persistent HPV 6 and 11 infections were identified in three students, who had pre-existing infections prior to vaccination, at the follow-up visit. Multivariate analysis uncovered independent associations, notably an increased risk of HPV infection in the oral tract among men who have sex with men. HPV prevalence rates remained low both before and after the vaccination scheme (T0: 14.7%, T1: 8.7%). Even after the full vaccination scheme, the prevalence remained similar at T2 (14.6%), with no statistically significant differences recorded. HPV11 emerged as the most prevalent type throughout the study, followed by HPV6. Vaccine genotypes were detected in a significant proportion of samples at T0 (85.4%), T1 (89.5%), and T2 (100%). Conclusion: Overall, this study suggests that vaccination may represent a promising approach to reducing HPV-related health risks. These findings shed light on the potential benefits and challenges of HPV vaccination, emphasizing the need for continued monitoring and vaccination efforts

Introdução: As infecções por papilomavírus humano (HPV) são de grande preocupação em homens, dada sua possível influência na saúde deles e no risco de transmissão para parceiros. Compreender e abordar essa infecção em homens é fundamental para avaliar a eficácia da vacinação na redução de doenças relacionadas ao HPV. Objetivo: Avaliar o impacto da vacinação contra o HPV, possíveis alterações genotípicas e efeitos adversos, por meio de um estudo prospectivo realizado em estudantes universitários do sexo masculino. Métodos: O estudo envolveu 286 voluntários examinados em Clínicas de Doenças Sexualmente Transmissíveis na Universidade Federal Fluminense, em Niterói, Rio de Janeiro, Brasil. A prevalência do HPV foi avaliada por polymerase chain reaction (PCR) genérico e genotipada por microarranjo de DNA, e foram monitorados os efeitos adversos. Resultados: Os resultados deste estudo revelaram a ausência de efeitos adversos moderados ou graves. Observaram-se mudanças genéticas, incluindo o desaparecimento dos tipos oncogênicos do HPV 16 e 18. Surpreendentemente, mesmo após a conclusão do esquema completo de vacinação, os estudantes ainda abrigavam o HPV 11 na cavidade oral. Além disso, foram identificadas infecções persistentes pelo HPV 6 e 11 em três estudantes que já tinham infecções preexistentes antes da vacinação e na visita de acompanhamento. A análise multivariada revelou associações independentes, especialmente um aumento no risco de infecção pelo HPV na cavidade oral em homens que têm relações sexuais com homens. As taxas de prevalência do HPV permaneceram baixas tanto antes quanto depois do esquema de vacinação (T0: 14,7%, T1: 8,7%). Mesmo após a conclusão do esquema de vacinação, a prevalência permaneceu semelhante em T2 (14,6%), sem diferenças estatisticamente significativas registradas. O HPV 11 emergiu como o tipo mais prevalente ao longo do estudo, seguido pelo HPV 6. Genótipos da vacina foram detectados em uma proporção significativa de amostras em T0 (85,4%), T1 (89,5%) e T2 (100%). Conclusão: No geral, este estudo sugere que a vacinação pode representar uma abordagem promissora para a redução dos riscos à saúde relacionados ao HPV. Esses achados lançam luz sobre os benefícios e desafios potenciais da vacinação contra o HPV, enfatizando a necessidade de monitoramento contínuo e esforços de vacinação

Human Papillomavirus infection in oral and anogenital sites: prevalence and rates of concordance / Infecção pelo Papilomavírus Humano em regiões orais e anogenitais: prevalência e taxa de concordância

Introduction: HPV infection causes cancer at several anatomical sites. However, the infection's natural history in non-cervical sites is understudied. Objective: To evaluate oral and anogenital HPV infections, correlating HPV prevalence rates and genotypes with site of infection and risk factors. Methods: In the present study, 351 samples from oral, genital, and anal sites of 117 patients were investigated by using PCR MY09/11 detection, followed by genotyping with RFLP. Results: HPV DNA prevalence was 89.7% (105/117) in genital lesions, 53.8% (63/117) in oral samples, and 58.9% (69/117) in anal samples. Regarding the risk factors associated with HPV in genital lesions, statistically significant rates for oral (p=0.039) and anal sex practices (p=0.0000012) were found. For oral samples, a relevant correlation concerning oral contraceptive use (p=0.039), tobacco smoking (p=0.036), and alcohol use (p=0.0075) were observed; whereas in anal samples, higher risk for HPV infection in patients who reported non-exclusive sexual partners (p=0.013) were found. The presence of viral DNA in all the three sites concurrently was observed in 36.8% of the cases (43/117). Among them, 18% (21/117) presented concordant HPV genotypes, diverging from the literature, and thus corroborating that there is still much to learn about HPV natural history, since different biological behaviors are expected within different populations. Differences in anatomy and physiology of the studied sites can determine different prevalence rates of infection by diverse genotypes. Conclusion: Due to the high prevalence of HPV DNA in extragenital sites, further studies are required to define aspects of HPV natural history among different human anatomical sites.

Introdução: As infecções causadas pelos papilomavírus humanos (HPV) são responsáveis pelo desenvolvimento de cânceres em diversos sítios anatômicos humanos. Entretanto, a história natural da infecção em sítios que não a cérvice uterina não é muito clara. Objetivo: Avaliar infecções orais, genitais e anais por HPV, correlacionando taxas de prevalência do vírus e seus genótipos aos sítios de infecção e a fatores de risco sócio-demográficos. Métodos: Em nosso estudo, investigamos 351 amostras coletadas dos sítios oral, genital e anal de 117 pacientes, por meio da técnica de PCR MY09/11, seguida de genotipagem por RFLP. Todos os pacientes apresentavam lesões genitais benignas. Resultados: A prevalência do HPV foi de 89,7% (105/117) nas lesões genitais, 53,8% (63/117) nas amostras orais e 58,9% (69/117) nas amostras anais. Em relação aos fatores de risco associados à infecção genital, encontramos diferenças estatísticas significativas para prática de sexo oral (p=0,039) e sexo anal (p=0,0000012). Já para as amostras orais, observamos importante correlação entre infecção e uso de contraceptivo oral (p=0,039), tabagismo (p=0,036) e uso de álcool (p=0,0075) enquanto nas amostras anais, alto risco de infecção pelo HPV foi associado a pacientes relatando parceiros sexuais não exclusivos (p=0,013). A presença do DNA viral simultaneamente nos três sítios estudados foi observada em 36,8% dos casos (43/117). Desses, 18% (21/117) apresentaram genótipos concordantes, diferindo da literatura, na qual há grande disparidade de descrições. Conclusão: Há a necessidade de novos estudos a fim de esclarecer a história natural do HPV em sítios extragenitais em diferentes populações, avaliando características anatômicas e fisiológicas com o intuito de esclarecer diferentes taxas de infecção por genótipos do HPV e diferentes processos de doença.

Evaluation of anogenital human papillomavirus infection in asymptomatic men from Rio de Janeiro, Brazil

Infection by human papillomavirus (HPV) is among the most prevalent sexually transmitted diseases worldwide. However, there are still gaps in the knowledge regarding the natural history of HPV infection in men. This study aimed to determine the prevalence of HPV infection in penile swab samples, derived from a clinically asymptomatic male population. For this purpose, 261 samples were collected between January 2011 and July 2013 in different institutions in the city of Rio de Janeiro. These samples were collected from the glans, corona, frenulum and coronal sulcus of the penis. Viral identification was made through generic and type-specific Polymerase Chain Reaction, and Restriction Fragment Length Polymorphism techniques. Prevalence of HPV infection was 16.5% (43 subjects). The most prevalent HPV type was HPV6 (34.9%), followed by HPV16 (23.3%), HPV11 (16.3%), HPV45 (9.3%) and HPV58 (2.3%). Hence, infection was associated with low-risk oncogenic types in 53.7% of the studied individuals, while high-risk oncogenic types were detected in 46.3%. Statistically significant results were found for the group of men who have sex with men, the group who have active anal intercourse, and subjects that lacked circumcision. After adjustments, sexual behavior and lack of circumcision remained as independent risk factors for HPV infection. We believe that these results may contribute to a clearer view about the circulation of HPV in the general male population, as well as to the identification of risk factors associated with the epidemiology of HPV infection in our state.