Prevalence of human papillomavirus (HPV) types 16 and 18 in cervical cancer in Stockholm, Sweden during 2019-2023 compared to 2003-2008.

BACKGROUND: The prevalence of different HPV types, especially HPV16 and 18 in cervical cancer in patients diagnosed 2019-2023 in Stockholm was compared to corresponding data from 2003-2008 before the introduction of HPV vaccination in Sweden. MATERIAL AND METHODS: Cervical cancer samples from 125 patients diagnosed 2019-2023 in Stockholm were analysed for 27 HPV types by multiplex assay and the HPV type prevalence data was compared to data obtained in 154 cervical samples from 2003-2008. RESULTS: Patient median age was higher 2019-2023 compared to 2003-2008 (55-years vs. 42-years, p = 0.046). Overall HPV prevalence was 93.6%, HPV16 and 18 accounted for 62.2% of all squamous cell carcinoma cases (SCC) and 63.6% of all adenocarcinoma cases (ADC) vs. 92.9%, 69.7% and 88.6% respectively 2003-2008. CONCLUSION: The joint prevalence of HPV16 and 18 in SCC and ADC tended to be slightly lower in 2019-2023 as compared to 2003-2008, but the difference was not statistically significant.

Dataset for vaginal human papillomavirus infection among adolescent and early adult girls in Jos, Nigeria.

OBJECTIVES: To assess risk factors for HPV infection, determine knowledge about HPV vaccines, assess willingness to receive the HPV vaccine among adolescent and early adult girls in Nigeria, we administered a structured questionnaire. We also collected samples to determine the prevalence and patterns of HPV infections. DATA DESCRIPTION: The dataset contains the responses of 205 participants from 10 randomly selected public and private secondary schools in Jos, Nigeria. The data includes information on risk factors for HPV infections such as sexual behaviours, knowledge about HPV vaccine and willingness to receive the vaccine. This is valuable information that can be compared to data from studies in other environments or to determine changes in the pattern of risk factors and HPV prevalence in this population over time.

Human papillomavirus spectrum of HPV-infected women in Nigeria: an analysis by next-generation sequencing and type-specific PCR.

BACKGROUND: Human papillomavirus (HPV) infection and cervical cancer are leading health problems and causes of death in many parts of the world. There are ~ 200 HPV types that can infect humans. This study aims to understand the spectrum of HPV infections in Nigerian women with normal or abnormal cytology. METHODS: We screened cervical samples from 90 women with possible HPV infections collected in two regional hospitals in Nigeria. The first screening was done using next-generation DNA sequencing (NGS), identifying multiple HPV types in many samples. Thereafter, type-specific PCR analysis was used to verify the NGS-identified HPV types in each sample. RESULTS: NGS analysis of the 90 samples from the Nigerian cohort identified 44 HPV types. The type-specific PCR confirmed 25 HPV types out of the 44 HPV types detected by NGS, and ~ 10 of these types were the most prevalent. The top five prevalent types found in the Nigerian cohort were HPV71 (17%), HPV82 (15%), HPV16 (16%), HPV6 (10%), and HPV20 (7%). Among the PCR-confirmed HPV types, we found 40.98% high-risk HPV types, 27.22% low-risk HPV types, and 31.15% undetermined HPV types. Among these 25 HPV types in Nigeria, only six were included in the current nine-valent HPV vaccine. We also observed strikingly high multiple HPV infections in most patients, with as many as nine HPV types in a few single samples. CONCLUSIONS: Our NGS-PCR approach of HPV typing in the Nigerian cohort samples unveiled all possible HPV types currently circulating in Nigerian people. We confirmed 25 HPV types using NGS and PCR, with many samples infected with multiple HPV types. However, only six of these types are part of the nine-valent HPV vaccines indicating the need to develop region-specific selective vaccines.

Dataset for Vaginal Human Papillomavirus infection among adolescent and early adult girls in Jos, Nigeria.

Objectives: To assess risk factors for HPV infection, determine knowledge about HPV vaccines, assess willingness to receive the HPV vaccine among adolescent and early adult girls in Nigeria, we administered a structured questionnaire. We also collected samples to determine the prevalence and patterns of HPV infections. Data description: The dataset contains the responses of 205 participants from 10 randomly selected public and private secondary schools in Jos, Nigeria. The data includes information on risk factors for HPV infections such as sexual behaviours, knowledge about HPV vaccine and willingness to receive the vaccine. This is valuable information that can be compared to data from studies in other environments or to determine changes in the pattern of risk factors and HPV prevalence in this population over time.

Genital Human Papillomavirus Infection in women from Florianópolis - Santa Catarina, Brazil / Infecção genital pelo Papilomavírus Humano em mulheres de Florianópolis - Santa Catarina, Brasil

Introduction: Human Papillomavirus (HPV) infection is the most common sexually transmitted infection in women. About 80% of sexually active women will have contact with this virus at some age in their lives. Most infections will be transient, but when the infection becomes persistent, associated with high oncogenic risk HPV, there may be progression to cancer, especially cervical cancer. The best way to prevent HPV infection is through the use of vaccines. Objective: To assess which are the most prevalent types of HPV in the city of Florianópolis, Brazil and if the majority of the diagnosed types are contained in the HPV vaccines currently available on the market and in the public health sector. Methods: More than 14,727 HPV tests were evaluated for the diagnosis of genital HPV infection in women from Florianópolis. The prevalence of infection was evaluated according to age of the women. HPV detection was performed using molecular biology tests, such as hybrid capture (for diagnosis of the HPV group, high or low oncogenic risk) and PCR (viral genotyping) techniques. Results: The diagnosis of HPV infection was made for women between one and 102 years of age. The highest positivity of the exams was observed in women aged 20­25 years (51% of the exams). The most prevalent age group was 31­35 years old (23.5%), and the lowest was for women aged 70 and above (0.6%). High oncogenic risk HPV was detected in 94.1% of positive samples and was the most frequent in all age groups. Mixed infection (high- and low-risk HPV) was more prevalent in the 66­70 age group (25.6%). The most frequent genotypes were non-16/18 high oncogenic risk HPV (77% of positive cases). HPV 16 was found in 17.1% of positive cases, and HPV 18 in 6.5%. Conclusion: The most prevalent types of HPV in Florianópolis in the last 6 years are non-16/18 high oncogenic risk HPV types, viral types not covered by the current HPV vaccine available in the public health sector in Brazil.

Introdução: A infecção pelo Papilomavírus Humano (HPV)é a infecção sexualmente transmissível mais frequente na mulher. Cerca de 80% das mulheres sexualmente ativas irão entrar em contato com este vírus em algum momento da sua vida. A maioria das infecções será transitória, mas quando a infecção se torna persistente, associada aos HPV de alto risco oncogênico, poderá haver a progressão para o câncer, principalmente o câncer de colo de útero. A melhor forma de prevenção da contaminação pelo HPV é através da utilização das vacinas. Objetivo: Avaliar quais são os tipos de HPV mais prevalentes na cidade de Florianópolis, Brasil, e se a maioria dos tipos diagnosticados estão contidos nas vacinas contra o HPV atualmente disponíveis no mercado e no setor público de saúde. Métodos: Foram avaliados 14.727 exames para diagnóstico da infecção genital pelo HPV em mulheres de Florianópolis, de acordo com a idade das mulheres. A detecção do HPV foi realizada através dos exames de biologia molecular pelas técnicas de captura híbrida (para diagnóstico do grupo de HPV, alto ou baixo risco oncogênico) e PCR (genotipagem viral). Resultados: Foram avaliados exames para diagnóstico da infecção de mulheres entre um e 102 anos de idade. A maior positividade dos exames foi observada em mulheres dos 20­25 anos (51% dos exames). A faixa etária de maior prevalência foi dos 31­35 anos (23,5%), e a menor, após os 70 anos (0,6%). O HPV de alto risco oncogênico foi detectado em 94,1% dos casos positivos e foi o mais frequente em todas as faixas etárias. A infecção mista (HPV de alto e baixo risco) foi mais prevalente na faixa etária dos 66­70 anos (25,6%). Os genótipos mais frequentes foram os HPV de alto risco oncogênico não 16/18 (77% dos casos positivos). O HPV 16 foi encontrado em 17,1% dos casos positivos, e o HPV 18 em 6,5%. Conclusão: Os tipos de HPV mais prevalentes em Florianópolis nos últimos 6 anos são os HPV de alto risco oncogênico não 16/18, tipos virais não cobertos pela atual vacina contra o HPV disponível no setor público de saúde do Brasil.Palavras-chave: HPV. Tipos de HPV. Câncer de colo de útero. Cobertura vacinal.

High APOBEC3B mRNA Expression Is Associated with Human Papillomavirus Type 18 Infection in Cervical Cancer.

The APOBEC3 (A3) proteins are cytidine deaminases that exhibit the ability to insert mutations in DNA and/or RNA sequences. APOBEC3B (A3B) has been evidenced as a DNA mutagen with consistent high expression in several cancer types. Data concerning the A3B influence on HPV infection and cervical cancer are limited and controversial. We investigated the role of A3B expression levels in cervical cancer in affected women positive for infection by different HPV types. Tumor biopsies from cancerous uterine cervix were collected from 216 women registered at Hospital do Câncer II of Instituto Nacional de Câncer, and infecting HPV was typed. A3B expression levels were quantified from RNA samples extracted from cervical biopsies using real-time quantitative PCR. Median A3B expression levels were higher among HPV18+ samples when compared to HPV16+ counterparts and were also increased compared to samples positive for other HPV types. In squamous cell carcinoma, HPV18+ samples also showed increased median A3B expression when compared to HPV Alpha-9 species or only to HPV16+ samples. Our findings suggest that A3B expression is differentially upregulated in cervical cancer samples infected with HPV18. A3B could be potentially used as a biomarker for HPV infection and as a prognostic tool for clinical outcomes in the context of cervical cancer.

Prevalence and distribution of selected cervical human papillomavirus types in HIV infected and HIV uninfected women in South Africa, 1989-2021: A narrative review.

Background: Human papillomavirus infection, a causative agent of cervical cancer, is of great concern, more so in populations with high HIV prevalence, such as South Africa. Aim: This review aimed to examine the prevalence and distribution of selected cervical human papillomavirus (HPV) types in HIV infected and HIV uninfected women in South Africa. Methods: PubMed and Web of Science databases were searched using key words. For data integrity, data was assessed by two authors independently. The study inclusion criteria comprised records on cervical HPV, HPV genotyping and HPV type distribution among South African women. Statistical analysis was performed using Social Science Statistics. Results: Sixty-nine articles met the inclusion criteria for analysis. Data on cervical HPV prevalence and type distribution was available only for five of the nine provinces of South Africa. Only 4/69 studies used sequencing as an approach to identify HPV types. In a general population, HPV type 16 was the most frequent (8.80%), followed by types 35 (4.86%), 18 (4.14%), 58 and 52 with the frequency of 3.65% and 3.62%, respectively. Furthermore, the least frequent type was HPV 70 (0.74%). Both HIV infected and HIV uninfected populations had a higher prevalence of high-risk human papillomavirus (hrHPV) types 16, 18 and 35 than other HPV types; while HPV types 6, 11 and 70 were the least frequent types from these populations. Lastly, HPV 16 was the most predominant type among women with normal (2.03%) and abnormal cervical cytology (6.60%). Conclusion: Expanding on HPV genotyping will improve the knowledge in patterns of HPV type distribution in South Africa that will further help in decision making to improve current diagnostics, and future vaccine development and assessment.

Merkel Cell Polyoma Virus and Cutaneous Human Papillomavirus Types in Skin Cancers: Optimal Detection Assays, Pathogenic Mechanisms, and Therapeutic Vaccination.

Oncogenic viruses are recognized to be involved in some cancers, based on very well-established criteria of carcinogenicity. For cervical cancer and liver cancer, the responsible viruses are well-known (e.g., HPV, HBV); in the case of skin cancer, there are still many studies which are trying to identify the possible viral etiologic agents as principal co-factors in the oncogenic process. We analysed scientific literature published in the last 5 years regarding mechanisms of carcinogenicity, methods of detection, available targeted therapy, and vaccination for Merkel cell polyomavirus, and beta human papillomavirus types, in relation to skin cancer. This review is targeted at presenting the recent findings which support the involvement of these viruses in the development of some types of skin cancers. In order to optimize the management of skin cancer, a health condition of very high importance, it would be ideal that the screening of skin cancer for these two analysed viruses (MCPyV and beta HPV types) to be implemented in each region's/country's cancer centres' molecular detection diagnostic platforms, with multiplex viral capability, optimal sensitivity, and specificity; clinically validated, and if possible, at acceptable costs. For confirmatory diagnosis of skin cancer, another method should be used, with a different principle, such as immunohistochemistry, with specific antibodies for each virus.

Genital infection by Human Papillomavirus (HPV) in women from Santa Catarina/Brazil / Infecção genital pelo Papilomavírus Humano (HPV) em mulheres de Santa Catarina/Brasil

Human Papillomavirus (HPV) infection is the most common sexually transmitted infection in women. About 80% of sexually active women will have contact with this virus at some point in their lives. Most infections will be transient, but when the infection becomes persistent and associated with a high oncogenic risk of Human Papillomavirus, there may be progression to cancer, especially cervical cancer. The best way to prevent Human Papillomavirus infection is through the use of vaccines, which have been available to the public in Brazil since 2014. Objective: This study aimed to assess the most prevalent types of Human Papillomavirus in the state of Santa Catarina, Brazil, and its mesoregions and if the majority of diagnosed types are contained in the Human Papillomavirus vaccines currently available on the market. Methods: A total of 20,000 Human Papillomavirus tests were evaluated for the diagnosis of genital Human Papillomavirus infection in women from the state of Santa Catarina, Brazil. The prevalence of infection was evaluated according to age and the city of origin of the exams. Human Papillomavirus detection was performed using molecular biology tests, such as hybrid capture (for diagnosis of the Human Papillomavirus group, high or low oncogenic risk) and polymerase chain reaction (viral genotyping) techniques. Results: The diagnosis of Human Papillomavirus infection was performed on women between 1 and 102 years of age. The age with the highest Human Papillomavirus positivity, as expected, was 20­25 years (45.6%) and the lowest after 70 years (7.1%). The highest Human Papillomavirus positivity of the exams was observed in the Serrana region of Santa Catarina state (58.9% of the exams). A high-oncogenic-risk Human Papillomavirus was detected in 93% of positive samples and was the most frequent in all age groups. Mixed infection (high- and low-risk Human Papillomavirus) was more prevalent in the 66­70 age group (29.3%) and in the Southern Region of Santa Catarina (26.4%). The most frequent genotypes in the state of Santa Catarina were non-16/18 high oncogenic risk Human Papillomavirus (76.9% of positive cases). Human Papillomavirus 16 was found in 17.1% of positive cases and Human Papillomavirus 18 in 6.6%. Conclusion: The most prevalent types of Human Papillomavirus in the state of Santa Catarina in the past 6 years are the non-16/18 high oncogenic risk Human Papillomavirus types, which are viral types not covered by the current Human Papillomavirus vaccines available in Brazil.

A infecção por Papilomavírus Humano é a infecção sexualmente transmissível mais frequente na mulher. Cerca de 80% das mulheres sexualmente ativas entrarão em contato com esse vírus em algum momento. A maioria das infecções será transitória, mas quando ela é persistente, associada aos Papilomavírus Humano de alto risco oncogênico, poderá progredir para câncer, principalmente de colo de útero. A melhor forma de se prevenir da contaminação pelo vírus é por meio de vacina, disponível no sistema público do Brasil desde 2014. Objetivo: Avaliar os tipos de Papilomavírus Humano mais prevalentes no estado de Santa Catarina e suas mesorregiões, e se a maioria dos tipos diagnosticados estão contidos nas vacinas contra o Papilomavírus Humano atualmente disponíveis no mercado. Métodos: Foram avaliados 20 mil exames para diagnóstico da infecção genital pelo Papilomavírus Humano em mulheres de todo o estado. A prevalência da infecção foi comparada de acordo com a idade e a procedência dos exames. A detecção do Papilomavírus Humano deu-se pelos exames de biologia molecular pelas técnicas de captura híbrida (para diagnóstico do grupo de Papilomavírus Humano, alto ou baixo riscos oncogênicos) e de PCR (genotipagem viral). Resultados: Foram avaliados exames para diagnóstico da infecção de mulheres entre um e 102 anos de idade. A faixa etária de maior positividade, como era de ser esperado, foi dos 20 aos 25 anos (45.6%) e a menor depois dos 70 anos (7.1%). A maior positividade dos exames foi observada na região Serrana do estado (58.9% dos exames). O Papilomavírus Humano de alto risco oncogênico foi detectado em 93% dos casos positivos e foi o mais frequente em todas as faixas etárias. A infecção mista (Papilomavírus Humano de alto e baixo riscos) foi mais prevalente na faixa etária dos 66 aos 70 anos (29.3%) e na região Sul Catarinense (26.4%). Os genótipos mais frequentes no estado foram os Papilomavírus Humano de alto risco oncogênico não 16/18 (76.9% dos casos positivos). O Papilomavírus Humano 16 foi encontrado em 17.1% dos casos positivos e o Papilomavírus Humano 18 em 6.6%. Conclusão:Os tipos de Papilomavírus Humano mais prevalentes no estado de Santa Catarina, nos últimos seis anos, são os Papilomavírus Humano de alto risco oncogênico não 16/18, tipos virais não cobertos pelas atuais vacinas contra o Papilomavírus Humano disponíveis no Brasil.

Minimal prevalence of HPV vaccination and common occurrence of high-risk HPV types in pregnant women with HIV: data from a national study in Italy.

Among 733 pregnant women with HIV followed between 2013 and 2021, only 8 (1.1%) had prior HPV vaccination. One had low-grade squamous intraepithelial lesions [LSIL], and none had HPV type information. Among the 725 non-vaccinated women, 578 (79.7%) had information on cervical cytology. Rate of cytologic abnormalities in this group was 20.6% (0.2% atypical glandular cells of undetermined significance [AGC], 1.7% atypical squamous cells of undetermined significance [ASC-US], 11.1% LSIL, and 7.6% high-grade squamous intraepithelial lesions [HSIL]). Among 56 women with HPV type information, 75.0% carried high risk types, with similar occurrence in women with and without cytologic abnormalities, 30.4% had multiple high-risk types, and 75.9% carried at least one of the types included in the currently recommended 9-valent vaccine.

Stratified Mucin-Producing Intraepithelial Lesion (SMILE) of the Uterine Cervix: High-Risk HPV Genotype Predominance and p40 Immunophenotype.

Stratified mucin-producing intraepithelial lesion (SMILE) is a rare high-grade cervical precancerous lesion designated a variant of adenocarcinoma in situ (AIS) in the WHO classification. We aimed to determine HPV genotypes, immunohistochemical phenotype and mucin presence in SMILE. Between 2010 and 2018, SMILE was diagnosed in 34 out of 6958 (0.5%) cervical biopsies, in 23 patients. Twenty-six tissue samples from twenty-one patients were available for further analysis, including 13 with SMILE alone, 12 with SIL and/or AIS and one with HSIL, AIS and endocervical adenocarcinoma. HPV genotyping was performed using the Seegene Anyplex II HPV 28 assay. Of the 26 samples, a single HPV genotype was identified in the majority of cases (n = 22), including 12/13 SMILEs associated with SIL/AIS. All but one were high-risk HPV genotypes (23/24; 96.8%). We identified seven different HPV genotypes, the most common being HPV16 (n = 10; 43.5%), HPV18 (n = 8, 34.8%) and HPV 31 (n = 5, 21.7%). All SMILEs showed a strong positive reaction to p16, CK7, CK19 and high Ki67 expression comparable to adjacent HSIL and/or AIS if present. SMILE showed variable mucin presence and p40-positive squamous differentiation suggesting phenotypic diversity in cervical precancerous lesions infected by single HPV.

Comparison of Aptima and hybrid capture-2 HPV tests and Pap test in the referral population in Japan.

The Aptima human papillomavirus (HPV) test (APTIMA) detects E6-E7 mRNA in abnormal cells in the uterine cervix. To investigate the accuracy of APTIMA for cervical cancer screening in Japan, 423 subjects, mostly referrals with abnormal cytology or being followed up for cervical intraepithelial neoplasia (CIN)1, were screened using two HPV tests, hybrid capture 2 (HC2) and APTIMA, and by the Pap test. Colposcopy was conducted in all subjects with a positive result in either test type. HPV genotyping was performed by Genosearch-31. A result of atypical squamous cells-undetermined significance (ASC-US) or worse on the HC2 test (ASC-US-HC2), and low-grade squamous intraepithelial lesion (LSIL) or worse (LSIL+) on the Pap test, was regarded as positive. APTIMA (97.5%) was more sensitive than LSIL+ (85.1%) for detecting CIN2 or worse (CIN2+) (McNemar test; p = .0003), and more sensitive (98.6%) than ASC-US-HC2 (92.7%) for detecting CIN3+. APTIMA and HC2 had similar sensitivities. HPV genotyping revealed that CIN2/3 with high-risk HPV (HR-HPV) was overlooked in five cases by ASC-US-HC2, and in four cases by HC2, while no such lesions were missed by APTIMA. Thus, APTIMA might be superior to HC2 for primary HPV screening in Japan. One cancer case positive for HPV67 (potentially high risk, [pHR]) was overlooked by Pap test and both HPV tests, suggesting a need for a new HPV test able to detect pHR-HPV types.

The frequency of high-risk human papillomavirus types, HPV16 lineages, and their relationship with p16INK4a and NF-κB expression in head and neck squamous cell carcinomas in Southwestern Iran.

High-risk human papillomaviruses (hr-HPVs) are the key risk factors implicated in the development of a significant proportion of head and neck squamous cell carcinomas (HNSCCs). We aimed to investigate the distribution of hr-HPV types and HPV16 lineages in a sample of patients with HNSCC and the possible association between HPV status and the expression of P16INK4A and NF-κB in Iranian HNSCC patients. We examined 108 formalin-fixed, paraffin-embedded (FFPE) histologically confirmed primary SCC tissue specimens of different head and neck anatomical sites. HPV types and HPV16 lineages were determined by nested PCR and overlapping nested PCR assays, respectively, followed by gene sequencing and phylogenetic analysis. The expression of p16INK4a and NF-κB was evaluated by immunohistochemistry. Twenty-five (23.1%) HNSCC tissue specimens were tested positive for HPV infection. The most prevalent HPV type was HPV-16, followed by HPV18 and HPV11. HPV16 variants belonged to the lineage A and lineage D which were further sorted into sublineages A1, A2, and D2. A significant association between HPV status and p16INK4a immunoreactivity was observed in more than 76% of the HPV-related HNSCCs (P < 0.0001). The overexpression of p16INK4a and cytoplasmic NF-κB was more common in low-grade HNSCC tumors. Our data highlights that HPV16, in particular the A2 sublineage, followed by A1 and D2 sublineages are the major agents associated with HNSCCs in Iran. Based on HPV16 predominance and its lineage distribution pattern, it seems that the prophylactic vaccines developed for cervical cancer prevention could also be applicable for the prevention of HPV-related HNSCCs in our population.

Transforming Properties of Beta-3 Human Papillomavirus E6 and E7 Proteins.

The beta human papillomaviruses (HPVs) are subdivided into 5 species (beta-1 to beta-5), and they were first identified in the skin. However, the beta-3 species appears to be more highly represented in the mucosal epithelia than in the skin. Functional studies have also highlighted that beta-3 HPV49 shares some functional similarities with mucosal high-risk (HR) HPV16. Here, we describe the characterization of the in vitro transforming properties of the entire beta-3 species, which includes three additional HPV types: HPV75, HPV76, and HPV115. HPV49, HPV75, and HPV76 E6 and E7 (E6/E7), but not HPV115 E6 and E7, efficiently inactivate the p53 and pRb pathways and immortalize or extend the life span of human foreskin keratinocytes (HFKs). As observed for HR HPV16, cell cycle deregulation mediated by beta-3 HPV E6/E7 expression leads to p16INK4a accumulation, whereas no p16INK4a was detected in beta-2 HPV38 E6/E7 HFKs. As shown for HPV49 E6, HPV75 and HPV76 E6s degrade p53 by an E6AP/proteasome-mediated mechanism. Comparative analysis of cellular gene expression patterns of HFKs containing E6 and E7 from HR HPV16, beta-3 HPV types, and beta-2 HPV38 further highlights the functional similarities of HR HPV16 and beta-3 HPV49, HPV75, and HPV76. The expression profiles of these four HPV HFKs show some similarities and diverge substantially from those of beta-3 HPV115 E6/E7 and beta-2 HPV38 E6/E7 HFKs. In summary, our data show that beta-3 HPV types share some mechanisms with HR HPV types and pave the way for additional studies aiming to evaluate their potential role in human pathologies.IMPORTANCE Human papillomaviruses are currently classified in different genera. Mucosal HPVs belonging to the alpha genus have been clearly associated with carcinogenesis of the mucosal epithelium at different sites. Beta HPV types have been classified as cutaneous. Although findings indicate that some beta HPVs from species 1 and 2 play a role, together with UV irradiation, in skin cancer, very little is known about the transforming properties of most of the beta HPVs. This report shows the transforming activity of E6 and E7 from beta-3 HPV types. Moreover, it highlights that beta-3 HPVs share some biological properties more extensively with mucosal high-risk HPV16 than with beta-2 HPV38. This report provides new paradigms for a better understanding of the biology of the different HPV types and their possible association with lesions at mucosal and/or cutaneous epithelia.

Multiple HPV Infections and Viral Load Association in Persistent Cervical Lesions in Mexican Women.

Persistent high-risk human papillomavirus (HR-HPV) infections play a major role in the development of invasive cervical cancer (CC), and screening for such infections is in many countries the primary method of detecting and preventing CC. HPV typing can be used for triage and risk stratification of women with atypical squamous cells of undetermined significance (ASC-US)/low-grade cervical lesions (LSIL), though the current clinical practice in Mexico is to diagnose CC or its preceding conditions mainly via histology and HR-HPV detection. Additional information regarding these HPV infections, such as viral load and co-infecting agents, might also be useful for diagnosing, predicting, and evaluating the possible consequences of the infection and of its prevention by vaccination. The goal of this follow-up hospital case study was to determine if HPV types, multiple HPV infections, and viral loads were associated with infection persistence and the cervical lesion grade. A total of 294 cervical cytology samples drawn from patients with gynecological alterations were used in this study. HPV types were identified by real-time PCR DNA analysis. A subset of HPV-positive patients was reevaluated to identify persistent infections. We identified HPV types 16, 18, and 39 as the most prevalent. One hundred five of the patients (59%) were infected with more than one type of HPV. The types of HPV associated with multiple HPV infections were 16, 18, and 39. In the follow-up samples, 38% of patients had not cleared the initially detected HPV infection, and these were considered persistent. We found here an association between multiple HPV infections and high viral loads with and infection persistence. Our findings suggest there are benefits in ascertaining viral load and multiple HPV infections status of HR-HPV infections for predicting the risk of persistence, a requirement for developing CC. These findings contribute to our understanding of HPV epidemiology and may allow screening programs to better assess the cancer-developing risks associated with individual HR-HPV infections.

Beta human papillomaviruses infection and skin carcinogenesis.

During the last decade, the worldwide incidence of keratinocyte carcinomas (KC) has increased significantly. They are now the most common malignancy, representing approximately 30% of all cancers. The role of ultraviolet (UV) radiation as a major environmental risk factor for skin cancers is well recognized. The aim of this review is to analyse the current understanding of the nature of beta-human papillomavirus (HPV) and its association with KC and explore the implications for the management and prevention of these cancers. A comprehensive review of the literature on beta-HPV and its association with KC was undertaken, the results reported in the form of a narrative review. A subgroup of HPV that infects the mucosal epithelia of the genital tract has been firmly associated with carcinogenesis. In addition, some HPV types with cutaneous tropism have been proposed to cooperate with UV in the development of KC. The first evidence for this association was reported in 1922 in patients with epidermodysplasia verruciformis (EV). Since then, epidemiological studies have highlighted the higher risk of skin cancer in patients with EV and certain cutaneous HPV types, and in vitro studies have elucidated molecular mechanisms and transforming properties of beta-HPV. Furthermore, in vivo research conducted on transgenic mice models has shown the possible role of beta-HPV in cutaneous carcinogenesis as a co-factor with UV radiation and immunosuppression. There is good evidence supporting the role of beta-HPV in the oncogenesis of KC. The high prevalence of beta-HPV in human skin and the worldwide burden of KC makes the search for an effective vaccine relevant and worthwhile.

Histomorphologic assessment and distribution of high-risk human papillomavirus (HPV) types in cervical high-grade squamous intraepithelial lesions with unusual histomorphologic features.

In rare cases, equivocal histomorphology ('deceiving dysplasia') does not allow immediate diagnosis of cervical high-grade squamous intraepithelial lesion (HSIL). We studied whether these cases are correlated with specific high-risk human papillomavirus (hr HPV) types. During 2011-2017, 39 cases of p16-positive cervical tissue biopsies with unusual ('deceiving') dysplastic histomorphology were identified and matched with the same number of controls (typical HSIL samples). Histomorphological characteristics were reviewed blindly and HPV testing was performed using the clinically validated RealTime test (Abbott) and Anyplex HPV 28 (Seegene). HPV 16 and HPV 31 were the two most frequent HPV types in both groups, although minimum, proportional, hierarchical and any etiological attribution estimates for HPV 16 were significantly lower in the deceiving group (13.2%, 21.3%, 23.7% and 23.7%) than in the control group (32.4%, 48.1%, 48.6% and 48.6%). In addition, the distribution of other hr HPV types differed between the two study groups, with five HPV types (HPV 56, 58, 59, 73 and 82) detected only in the deceiving group. Histomorphologic review of both groups (regardless of HPV type) confirmed significant differences in nuclear atypia, maximum lesion thickness and cellularity, although these were diminished when cross-comparisons between HPV16/18 and non-HPV16/18 cases pooled from both study groups were evaluated. Different attribution estimates for HPV 16, HPV 16/18 and non-16/18 hr HPV types in deceiving and control groups were observed, in particular for HPV 16. However, an unusual (deceiving) histomorphology may also depend on unknown HPV-related molecular changes.

Factors associated with human papillomavirus infection - findings from a cervical cancer screening program for female employees in Beijing.

BACKGROUND: In 2018, the Beijing Federation of Trade Unions organized a cervical cancer screening program for female employees for the first time. This study aimed to investigate the screening results of this program and determine the factors associated with human papillomavirus (HPV) infection. METHODS: A total of 8297 female employees participating in the screening program between January 1, 2018, and December 31, 2018, were enrolled in this study. The methods for screening cervical cancer included ThinPrep cytology test (TCT) and HPV genotyping test. Single-factor analysis and multiple binary logistic regression analysis were used to identify the factors associated with HPV infection. RESULTS: Of the 8297 women (median age: 43.00 years), TCT was found to be abnormal in 116 patients (1.40%) and 1169 (14.09%) were positive for HPV genotyping test. Notably, HPV-52 was the most prevalent subtype (3.05%), followed by HPV-16 (2.82%), HPV-58 (2.01%), HPV-51 (1.58%) and HPV-56 (1.49%). Multivariate logistic regression analysis revealed that taxi drivers (OR =1.98; 95% CI =1.31-2.99) and single women with a history of sexual activity (OR =2.32; 95% CI =1.41-3.82) were significantly associated with an increased risk of HPV infection (P<0.05), whereas medical workers (OR =0.67; 95% CI =0.51-0.88) and factory workers (OR =0.36; 95% CI =0.17-0.77) were protective factors for HPV infection (P<0.05). CONCLUSION: HPV-52, HPV-16 and HPV-58 are the most common types of high-risk HPV among female employees in Beijing. Being taxi drivers and single women with a history of sexual activity are significantly associated with the risk of HPV infection.

Cancer susceptibility of beta HPV49 E6 and E7 transgenic mice to 4-nitroquinoline 1-oxide treatment correlates with mutational signatures of tobacco exposure.

We have previously showed that a transgenic (Tg) mouse model with cytokeratin 14 promoter (K14)-driven expression of E6 and E7 from beta-3 HPV49 in the basal layer of the epidermis and of the mucosal epithelia of the digestive tract (K14 HPV49 E6/E7 Tg mice) are highly susceptible to upper digestive tract carcinogenesis upon exposure to 4-nitroquinoline 1-oxide (4NQO). Using whole-exome sequencing, we show that in K14 HPV49 E6/E7 Tg mice, development of 4NQO-induced cancers tightly correlates with the accumulation of somatic mutations in cancer-related genes. The mutational signature in 4NQO-treated mice was similar to the signature observed in humans exposed to tobacco smoking and tobacco chewing. Similar results were obtained with K14 Tg animals expressing mucosal high-risk HPV16 E6 and E7 oncogenes. Thus, beta-3 HPV49 share some functional similarities with HPV16 in Tg animals.