Genital Human Papillomavirus Types Research Articles

Global and regional estimates of genital human papillomavirus prevalence among men: a systematic review and meta-analysis

The epidemiology of human papillomavirus (HPV) in women has been well documented. Less is known about the epidemiology of HPV in men. We aim to provide updated global and regional pooled overall, type-specific, and age-specific prevalence estimates of genital HPV infection in men. We conducted a systematic review and meta-analysis to assess the prevalence of genital HPV infection in the general male population. We searched Embase, Ovid MEDLINE, and the Global Index Medicus for studies published between Jan 1, 1995, and June 1, 2022. Inclusion criteria were population-based surveys in men aged 15 years or older or HPV prevalence studies with a sample size of at least 50 men with no HPV-related pathology or known risk factors for HPV infection that collected samples from anogenital sites and used PCR or hybrid capture 2 techniques for HPV DNA detection. Exclusion criteria were studies conducted among populations at increased risk of HPV infection, exclusively conducted among circumcised men, and based on urine or semen samples. We screened identified reports and extracted summary-level data from those that were eligible. Data were extracted by two researchers independently and reviewed by a third, and discrepancies were resolved by consensus. We extracted only data on mucosal α-genus HPVs. Global and regional age-specific prevalences for any HPV, high-risk (HR)-HPV, and individual HPV types were estimated using random-effects models for meta-analysis and grouped by UN Sustainable Development Goals geographical classification. We identified 5685 publications from database searches, of which 65 studies (comprising 44 769 men) were included from 35 countries. The global pooled prevalence was 31% (95% CI 27-35) for any HPV and 21% (18-24) for HR-HPV. HPV-16 was the most prevalent HPV genotype (5%, 95% CI 4-7) followed by HPV-6 (4%, 3-5). HPV prevalence was high in young adults, reaching a maximum between the ages of 25 years and 29 years, and stabilised or slightly decreased thereafter. Pooled prevalence estimates were similar for the UN Sustainable Development Goal geographical regions of Europe and Northern America, Sub-Saharan Africa, Latin America and the Caribbean, and Australia and New Zealand (Oceania). The estimates for Eastern and South-Eastern Asia were half that of the other regions. Almost one in three men worldwide are infected with at least one genital HPV type and around one in five men are infected with one or more HR-HPV types. Our findings show that HPV prevalence is high in men over the age of 15 years and support that sexually active men, regardless of age, are an important reservoir of HPV genital infection. These estimates emphasise the importance of incorporating men in comprehensive HPV prevention strategies to reduce HPV-related morbidity and mortality in men and ultimately achieve elimination of cervical cancer and other HPV-related diseases. Instituto de Salud Carlos III, European Regional Development Fund, Secretariat for Universities and Research of the Department of Business and Knowledge of the Government of Catalonia, and Horizon 2020. For the Spanish and French translations of the abstract see Supplementary Materials section.

Four conserved amino acids on human papillomavirus E6 predict clinical high-risk types.

Human papillomavirus (HPV) types included in the genus alpha papillomavirus (alpha-HPVs) are subdivided into high- and low-risk HPVs associated with tumorigenicity. According to conventional risk classification, over 30 alpha-HPVs remain unclassified and HPV groups phylogenetically classified using the L1 gene do not exactly correspond to the conventional risk classification groups. Here, we propose a novel cervical lesion progression risk classification strategy. Using four E6 risk distinguishable amino acids (E6-RDAAs), we successfully expanded the conventional classification to encompass alpha-HPVs and resolve discrepancies. We validated our classification system using alpha-HPV-targeted sequence data of 325 cervical swab specimens from participants in Japan. Clinical outcomes significantly correlated with the E6-RDAA classification. Four of five HPV types in the data set that were not conventionally classified (HPV30, 34, 67, and 69) were high-risk according to our classification criteria. This report sheds light on the carcinogenicity of rare genital HPV types using a novel risk classification strategy.

Interactions of the protein tyrosine phosphatase PTPN3 with viral and cellular partners through its PDZ domain: insights into structural determinants and phosphatase activity.

The human protein tyrosine phosphatase non-receptor type 3 (PTPN3) is a phosphatase containing a PDZ (PSD-95/Dlg/ZO-1) domain that has been found to play both tumor-suppressive and tumor-promoting roles in various cancers, despite limited knowledge of its cellular partners and signaling functions. Notably, the high-risk genital human papillomavirus (HPV) types 16 and 18 and the hepatitis B virus (HBV) target the PDZ domain of PTPN3 through PDZ-binding motifs (PBMs) in their E6 and HBc proteins respectively. This study focuses on the interactions between the PTPN3 PDZ domain (PTPN3-PDZ) and PBMs of viral and cellular protein partners. We solved the X-ray structures of complexes between PTPN3-PDZ and PBMs of E6 of HPV18 and the tumor necrosis factor-alpha converting enzyme (TACE). We provide new insights into key structural determinants of PBM recognition by PTPN3 by screening the selectivity of PTPN3-PDZ recognition of PBMs, and by comparing the PDZome binding profiles of PTPN3-recognized PBMs and the interactome of PTPN3-PDZ. The PDZ domain of PTPN3 was known to auto-inhibit the protein's phosphatase activity. We discovered that the linker connecting the PDZ and phosphatase domains is involved in this inhibition, and that the binding of PBMs does not impact this catalytic regulation. Overall, the study sheds light on the interactions and structural determinants of PTPN3 with its cellular and viral partners, as well as on the inhibitory role of its PDZ domain on its phosphatase activity.

Assessment of the State of Knowledge about HPV Infection and HPV Vaccination among Polish Resident Doctors.

HPV (human papillomavirus) vaccinations have been introduced into the population of many countries through vaccination programs, although their acceptance varies from country to country, largely dependent on the state of knowledge about diseases caused by genital HPV types as well as cultural, social, and religious factors. The aim of the study was to analyze the state of knowledge about HPV and HPV vaccines among doctors during their specialization in gynecology and obstetrics, dermatology and venereology, and pediatrics. Another objective of the study was to analyze the impact of the state of knowledge about HPV vaccination on their attitude to primary prevention, i.e., vaccinations. A questionnaire was used to collect the data and 639 doctors took part in the study. The analysis was carried out mainly using descriptive statistical methods. In Poland, doctors’ knowledge about HPV is low, independent of gender, age, and subject of specialization. Doctors’ knowledge about the HPV vaccine is very low and independent of sex, age, and subject of specialization. However, doctors’ knowledge about HPV and the HPV vaccine influences the attitude to HPV vaccination and does not affect pro-active behaviors.

Structural and functional characterization of the PDZ domain of the human phosphatase PTPN3 and its interaction with the human papillomavirus E6 oncoprotein

The human protein tyrosine phosphatase non-receptor type 3 (PTPN3) is a PDZ (PSD-95/Dlg/ZO-1) domain-containing phosphatase with a tumor-suppressive or a tumor-promoting role in many cancers. Interestingly, the high-risk genital human papillomavirus (HPV) types 16 and 18 target the PDZ domain of PTPN3. The presence of a PDZ binding motif (PBM) on E6 confers interaction with a number of different cellular PDZ domain-containing proteins and is a marker of high oncogenic potential. Here, we report the molecular basis of interaction between the PDZ domain of PTPN3 and the PBM of the HPV E6 protein. We combined biophysical, NMR and X-ray experiments to investigate the structural and functional properties of the PDZ domain of PTPN3. We showed that the C-terminal sequences from viral proteins encompassing a PBM interact with PTPN3-PDZ with similar affinities to the endogenous PTPN3 ligand MAP kinase p38γ. PBM binding stabilizes the PDZ domain of PTPN3. We solved the X-ray structure of the PDZ domain of PTPN3 in complex with the PBM of the HPV E6 protein. The crystal structure and the NMR chemical shift mapping of the PTPN3-PDZ/peptide complex allowed us to pinpoint the main structural determinants of recognition of the C-terminal sequence of the E6 protein and the long-range perturbations induced upon PBM binding.

Seroprevalences of Antibodies to 11 Human Papillomavirus (HPV) Types Mark Cumulative HPV Exposure

The antibody responses against human papillomavirus type 16 (HPV-16) and HPV-18 are well known, but many genital HPV types are oncogenic. We assessed the correlation between detection of type-specific HPV DNA and antibodies for 11 HPV types. A total of 2024 women attending the organized national cervical cancer screening program in Slovenia were tested for cervical high-risk HPV DNA (HPV-16, -18, -31, -33, -35, -39, -45, -52, -56, -58, -59, and -68) and serum anti-HPV antibodies. Of these, 1848 women were tested with the same methods 3 years earlier. Type-specific antibodies against 10 of 11 HPV types (HPV-16, -18, -31, -33, -35, -39, -45, -52, -56, and -58) were associated with concomitant presence of type-specific DNA (median odds ratio [OR], 7.5; 95% confidence interval [CI], 2.2-26.1). When the concomitant presence of type-specific HPV DNA at the 3-year visit was combined with the presence of the same HPV DNA type 3 years earlier, the statistical precision was greatly improved, and antibodies against all 11 types (HPV-16, -18, -31, -33, -35, -39, -45, -52, -56, -58, and -59) were associated with the presence of DNA of the same HPV type (median OR, 7.4; 95% CI, 4.2-12.8). Sensitivity had a slight tendency to increase (from 47% to 52%) when DNA positivity at the earlier time point was included, whereas specificity was the same (88%). Seroconversion was associated with previous HPV DNA positivity. Seropositivity mostly remained stable during the observation period. For 11 HPV types, type-specific seropositivity was associated with the presence of DNA of the same HPV type (either concomitantly or previously). Antibodies to these HPV types mark cumulative HPV exposure.

Abstract 5750: USP15 inhibits HPV16 E6 degradation and catalytically inactive USP15 has reduced inhibitive activity

Abstract HPVs can be classified as either high-risk or low-risk depending on the transforming potential of the virus. Most cervical cancers and a significant proportion of other anogenital cancers have been associated with infection by a small number of high-risk genital HPV types. Tumorigenesis induced by high-risk genital HPVs has been linked to the expression of two viral oncoproteins, E6 and E7, which cooperate in cellular immortalization and transformation processes. HPV16 E6 is an oncoprotein that causes the development of high-risk type human papilloma virus (HPV) and induces cancers, including oropharyngeal, anal, and cervical cancers. The stability of E6 is essential for its complete function as an oncoprotein. Using the yeast two-hybrid system, we identified ubiquitin-specific protease 15 (USP15) as an HPV16 E6-interacting protein. USP15 encodes a protein that consist of 952 amino acids and functions as a deubiquitinating enzyme. Deubiquitination is an essential process that releases ubiquitin chains from ubiquitin-protein conjugates. Aberrations in the ubiquitin-proteasome system have been recently connected to the pathogenesis of several human protein degradation disorders, including cancer and neurodegenerative diseases; as such, the proteasome is now considered to be important in the mechanism of carcinogenesis. USP15 cleaves polyubiquitin chains of HPV16 E6 and/or ubiquitin precursors. Immunohistochemical analysis showed that USP15 was highly expressed in normal cervical squamous cells, and cervical cancer cells. Our results indicated that USP15 can increase the level of HPV16 E6 by inhibiting E6 degradation. USP15 dose-dependently inhibited the degradation of HPV16 E6. In contrast, catalytically inactive mutants of USP15 had a reduced inhibitory effect on E6 degradation. In particular, USP15 mutants of all three cysteine boxes and the NHL mutant of the KRF box had a drastically reduced inhibitive effect on HPV16 E6 degradation. In addition, HPV16 E6 mRNA was not induced by USP15; therefore, HPV16 E6 appears to be post-translationally regulated. These results suggest that USP15 has the ability to stabilize E6 as a deubiquitinating enzyme, and HPV16 E6 can affect biological functions as an oncoprotein in infected human cells. Citation Format: Aoi Tokuda, Masafumi Yoshimoto, Yuji Yaginuma. USP15 inhibits HPV16 E6 degradation and catalytically inactive USP15 has reduced inhibitive activity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5750. doi:10.1158/1538-7445.AM2017-5750

Genome-wide discovery of viral microRNAs based on phylogenetic analysis and structural evolution of various human papillomavirus subtypes.

In mammals, microRNAs (miRNAs) play key roles in controlling posttranscriptional regulation through binding to the mRNAs of target genes. Recently, it was discovered that viral miRNAs may be involved in human cancers and diseases. It is likely that viral miRNAs help viruses enter the latent phase of their life cycle and become undetected by the host's immune system, while increasing the host's risk for cancer development. Cervical cancer is typically related to the infection of human papillomavirus (HPV) through sexual transmission. To further understand the molecular mechanisms underlying the associations of HPV infection with genital diseases, we developed a systematic method for viral miRNA identification and viral miRNA-mediated regulatory network construction based on genome-wide sequence analysis. The complete genomes of certain high-risk HPV subtypes were used to predict putative viral pre-miRNAs by bioinformatics approaches. In addition, small RNA libraries in human cervical lesions from existing publications were collected to validate the predicted HPV pre-miRNAs. For the construction of virally encoded miRNA-mediated regulatory network of HPV infection, cervical squamous epithelial carcinoma gene expression data were extracted from the RNA sequencing platform in The Cancer Genome Atlas; the differentially expressed genes were used to identify the putative targets of viral miRNAs. Predicted cellular target genes of HPV-encoded miRNAs provide an overview of these viral miRNA's putative functions. Finally, a large-scale genome analysis was carried out to examine the phylogenetic relationship and structural evolution among genital HPV types that have the potential to cause genital cancer. In this study, we discovered putative HPV-encoded miRNAs, which were validated against the small RNA libraries in human cervical lesions. Furthermore, as indicated by their biological functions, host genes targeted by HPV-encoded miRNAs may play significant roles in virus infection and carcinogenesis. These viral miRNAs pose as promising candidates for the development of antiviral drugs. More importantly, the identified subtype-specific miRNAs have the potential to be used as biomarkers for HPV subtype determination.

Human papillomavirus vaccination in men who have sex with men - what will be required by 2020 for the same dramatic changes seen in heterosexuals.

This paper addresses the issue of whether men who have sex with men (MSM) will share the spectacular reductions in human papillomavirus (HPV) infection and its associated neoplasia that we are currently witnessing in heterosexuals. The reproductive rate for HPV infection in heterosexuals is not well established, but 70% vaccination coverage in women has resulted in a fall of more than 90% in genital warts and HPV types 16/18 in young women and 80% fall in young men indicating that the critical vaccination threshold has been exceeded for this group. Published data on the three elements of the reproductive rate for HPV infection (i.e. transmission probability per sexual partnership, rate of partner change and duration of infectiousness) suggest they are higher in MSM than heterosexuals. This indicates that the reproductive rate for HPV will be higher in MSM and hence the critical vaccination threshold will also be higher. But while vaccinating 70% of girls protect 70% of sexual partnerships in heterosexuals, vaccinating 70% of boys protect more than 70% of partnerships in MSM. Only 9% (30% by 30%) of sexual partnerships in MSM are not protected with 70% coverage. Therefore vaccinating 70% of boys will protect 91% of sexual partnerships in MSM. However the efficacy of the HPV vaccine is much lower when sexually active MSM are vaccinated rather than boys. We argue that if MSM are to have the same benefit from the HPV vaccine that heterosexuals had, boys and not adult MSM will need to be vaccinated.

Association Between Vaginal Douching and Genital Human Papillomavirus Infection Among Women in the United States

The very few studies that have examined the association between vaginal douching and genital human papillomavirus (HPV) infection have found contrary results. We investigated the associations between douching and numbers of HPV genotypes infecting 1271 participants aged 20-49 years in the 2003-2004 US National Health and Nutrition Examination Survey. After controlling for relevant covariates, douching in the past 6 months was significantly associated with infection by higher numbers of all genital HPV types (relative risk ratio, 1.26; 95% confidence interval, 1.03-1.54) and HPV high-risk types (1.40; 1.09-1.80).

Sexually transmitted infections in children as a marker of child sexual abuse and direction of future research.

This review considers recent evidence on sexually transmitted infections (STIs) as a marker of child sexual abuse (CSA), when diagnosed after the neonatal period. It also aims to identify if there are specific areas where additional research is required. An evidence-based systematic review using strict inclusion criteria shows that CSA is a major cause of STIs in children. In children 12 years and below, 36-83% of Neisseria gonorrhoeae and 75-94% of Chlamydia trachomatis infections are due to CSA; for children 14 years and younger, 31-58% of anogenital warts are due to CSA. In child genital sampling, genital human papillomavirus (HPV) types were more common in those considered abused (13.7%) than nonabused (1.3%). HPV typing of genital warts in children were all of genital type 6. Subsequent research, into N. gonorrhoeae, C. trachomatis, Trichomonas vaginalis and syphilis in children including ophthalmic infection, found that 13 of 15 cases were confirmed/likely due to CSA. Recent data indicate that bacterial vaginosis and Mycoplasma genitalium are related to sexual activity in adults but did not assess children. STIs in children under 13-14 years may indicate CSA. Genital HPV types are associated with CSA. Research is required of sufficient standard to contribute to the evidence base.

Medical and sociodemographic factors associated with human papillomavirus (HPV) vaccination adherence among female survivors of childhood cancer.

Among those 9-26 years of age, vaccination can prevent specific types of genital human papillomavirus (HPV), the most common sexually transmitted infection and cause of cervical and other cancers. The objective of this study was to estimate the prevalence of and factors associated with HPV vaccine initiation and completion among females surviving childhood cancer. One-hundred fourteen young adults and 230 mothers with daughters surviving childhood cancer completed surveys querying HPV vaccination history along with medical and sociodemographic factors potentially associated with vaccination outcomes. Vaccination rate differences by age necessitated analysis of outcomes by age group: 9-13 years (preadolescents), 14-17 years (adolescents), and 18-26 years (young adults). Multivariable logistic regression was utilized to identify factors associated with HPV vaccination outcomes. Overall, 34.6% (119/344) of survivors initiated and 20.9% (72/344) completed HPV vaccination. Preadolescents were least likely to have initiated vaccination (P < 0.001). Physician recommendation was associated with initiation across age groups (OR = 6.81-11.96, Ps < 0.001-.01), whereas older age at diagnosis (≥12 years of age) was associated with lower vaccination initiation among young adults only (OR = 0.28; 95%CI, 0.10-0.76, P = 0.012). Physician recommendation (OR = 7.54; 95%CI, 1.19-47.69, P = 0.032; adolescent group) and greater treatment intensity (OR = 5.25; 95%CI, 1.00-27.61, P = 0.050; young adult group) were associated with vaccine completion, whereas being non-White was associated with decreased vaccination completion (OR = 0.17; 95%CI, 0.05-0.66, P = 0.010; adolescent group). A minority of youths surviving childhood cancer have initiated or completed HPV vaccination. Strategies to increase vaccination among survivors are discussed.

Genotyping of High Risk Human Papillomavirus (HPV) among cervical precancer and cancer patients

Introduction: Human papillomavirus (HPV) is a DNA virus which has tropism for epithelial cells, is the major etiological factor for development of cervical precancerous and cancerous lesions. Nearly 100 diff erent types of HPV have been characterized and thereare a large number of other types. HPV infection is one of the most common causes of sexually transmitted disease in both men and women worldwide. It is associated with a variety of clinical conditions that range from innocuous lesions to cancer. Genital HPV types are divided into high and low-risk types, according to the oncogenic potential. Molecular and epidemiologic studies have solidifi ed the association between high risk HPV types (especially HPV-16 and HPV-18) and cervical squamous cell carcinoma. HPV infection is often transient and self-limiting but infection may persists and progress to high grade lesions and cancer. In addition to persistent high-risk HPV infection, other viral factors such as high viral loads, HPV variants, infections with multiple high-risk HPV types and genetic predisposition contribute to the development of cervical cancer. Th e aim of the present study was to detect HPV DNA and identify high risk HPV genotype among women having cervical intraepithelial neoplasia and carcinoma and to evaluate potential effi cacy of prophylactic HPV vaccine. Methods: Cervical swab from histopathologically diagnosed CIN (n=51) and carcinoma (n=39) patients were taken and high risk HPV DNA was detected by HC II assay. Polymerase Chain Reaction was used to identify high risk HPV genotype. Result: HPV DNA was detected in 41 (45.56%) patients by HC II assay. HPV type 16 was detected in 27 (81.82%) followed by type 18 in 3 (9.09%) and type 45 in 2 (6.06%) cases of cervical carcinoma. Among precancerous cases, only type 16 was detected. Conclusion: Knowledge based on HPV prevalence and genotype could be used to predict the effi cacy of cost eff ective prophylactic vaccine, introduction of newer generation vaccine and management of cervical carcinoma.

Low doses of flagellin-L2 multimer vaccines protect against challenge with diverse papillomavirus genotypes

Genetically modified bacterial flagellin (Fla), a Toll-like receptor-5 (TLR5) ligand, was evaluated as a fusion partner for human papillomavirus (HPV) L2-based immunogens in two animal challenge models; either cutaneous inoculation of rabbits with HPV ‘quasivirions’ containing cottontail rabbit papillomavirus (CRPV) genomes that induce warts, or intra-vaginal inoculation of mice with HPV ‘pseudovirions’ encapsidating a luciferase reporter plasmid and measurement of bioluminescence to determine infectivity. An Escherichia coli production system was developed for flagellin-L2 (Fla-L2) fusions containing either monomeric HPV-16 L2 a.a. 11(×11–200) or oligomeric L2 comprising a fusion of the a.a. 11–88 peptides of five (Fla∼5×11–88) or eight (Fla∼8×11–88) genital HPV types. Immunogenicity and bioactivity of Fla-L2 constructs were assessed using an in vitro neutralization and cell-based TLR-5 binding assay, respectively. Efficacy was evaluated following active immunization of rabbits or mice administered 3 intramuscular doses of Fla-L2 recombinants without exogenous adjuvant, followed by challenge. In addition, passive immunization studies of naïve rabbits with serial dilutions of pooled immune sera were used to determine End-Point Protection Titers (EPPT) for each formulation against a broader spectrum of HPV quasivirions. Efficacy was assessed for up to 10 weeks on the basis of wart volume induced following challenge and results compared to licensed L1-VLP vaccines (Gardasil and Cervarix). Following active immunization at doses as low as 1μg, Fla-L2 fusions afforded complete protection against infection (mice) and disease (rabbits) following either homologous or heterologous HPV challenge. Passive immunization with anti-L2 immune sera discriminated between the different vaccine candidates under evaluation, demonstrated the protective role of antibody and suggested the superiority of this oligomeric L2-TLR5 agonist fusion approach compared to L1-based vaccines in its ability to cross-protect against non-vaccine HPV types.

Prevalence of Human Papillomavirus in Anal and Oral Sites Among Patients with Genital Warts

Genital warts are caused by human papillomavirus (HPV). HPV is a leading cause of anogenital malignancies and a role of HPV in the aetiology of oro-pharyngeal cancers has been demonstrated. The frequency of oral HPV infection in patients with genital warts and the association between concomitant genital, anal and oral infection is unclear. A total of 201 men and women with genital wart-like lesions were recruited. Swab samples were obtained from the genital warts and the anal canal and an oral rinse was collected. Anal HPV was found in 46.2% and oral HPV in 10.4% of the participants. Concordance between anal and genital wart HPV types was 78.1%, while concordance between oral and genital wart types was 60.9%. A lower concordance of 21.7% was observed between anal and oral HPV types. Significantly more women than men had multiple HPV types and anal HPV. In conclusion, extra genital HPV is common in patients with genital warts. A gender inequality seems to exist.

Pre-vaccination seroprevalence of 15 human papillomavirus (HPV) types among women in the population-based Slovenian cervical screening program

ObjectivesTo estimate seroprevalence of 11 high-risk (hr) HPV types and four low-risk (lr) HPV types among 20–64 years old Slovenian women participating in the population-based cervical cancer screening program. MethodsSerum samples from 3259 women were tested for HPV type-specific antibodies with a multiplexed pseudovirion-based serological assay (PsV-Luminex). ResultsSeropositivity for any of the 15 HPV types was 65.7%, any of the 11 hr-HPV types 59.2%, and any of the four lr-HPV types 33.1%. Antibodies against at least one of the four vaccine HPV types (HPV 6, 11, 16, 18) were detected in 40.8% women. Among hr-HPV types, seropositivity was highest for HPV 16 (25.2%) and among lr-HPV types for HPV 6 (19.1%). Age-specific HPV16 seropositivity was highest among 30–39 years old (29.6%) and decreased with increasing age to 14.0% among 60–64 years old. ConclusionThe lifetime sexual exposure to genital HPV types is substantial, emphasising the need for HPV vaccination.

Solitary epidermolytic acanthoma

Solitary epidermolytic acanthoma is thought to be an uncommon lesion. It can present as a solitary, localized or disseminated process that is unrelated to the genetic form of icthyosis. A retrospective review of solitary epidermolytic acanthomas was performed at the Ackerman Academy of Dermatopathology, NY, over a 2 year period. The clinical and histopathological features of solitary epidermolytic acanthomas were described in 64 biopsies from 60 individuals. In situ hybridization for human papillomavirus (HPV) was performed on all genital lesions. The incidence of epidermolytic acanthomas in our series was higher than previously reported (27.8/100,000). Genital location was the most common and the incidence of genital lesions was 8/100,000. In situ hybridization showed no evidence of genital HPV types within the lesions. The histological features of solitary epidermolytic acanthoma were re-evaluated. Genital skin was the most common location for solitary epidermolytic acanthoma, but we found no evidence to suggest a role for genital HPV types. A strong male predominance was noted, and the lesions demonstrate a wide range of clinical and pathological findings.

Metagenomic sequencing of “HPV-negative” condylomas detects novel putative HPV types

Condylomas are caused by human papillomavirus (HPV), but may in rare cases be “negative for HPV” by PCR. Metagenomic sequencing can be used for an unbiased assessment of the presence of virus. Ten swab sample pools, each containing four cases of “HPV-negative” condylomas, were subjected to metagenomic sequencing. One pool contained Molluscum contagiosum. Five pools contained HPV, of which three pools contained novel putative HPV-types. The 12 samples in these three pools were sequenced individually. Six of these contained HPV and two contained Molluscum contagiosum. Altogether, 1337 HPV-related reads were detected, representing 23 novel putative Gammapapillomaviruses, 10 established HPV types (genital HPV types 6, 57, 58 and 66, Betapapillomavirus types 5, 105, 124, and Gammapapillomavirus types 50, 130, 150) and two described HPV sequences (KC7 and FA69). Complete genomes of Gammapillomavirus FA69 and SE87 were compiled. Metagenomic sequencing reveals that seemingly “HPV-negative” condylomas contain known and previously unknown HPV types.

Sequence variation of human papillomavirus Type 31 long control region: Phylogenetic and functional implications

About one-third of human papillomavirus (HPV) types infect the anogenital tract. High-risk genital HPV types (such as HPV 16, 18, 31, 33, and 35) are linked causally to the development of cervical cancer. The long control region (LCR) of the HPV genome regulates the replication and transcription of the viral genome. In this study, the functional significance of nucleotide sequence variation within the LCR of HPV 31 was investigated. The LCR was amplified by polymerase chain reaction (PCR) from 41 HPV 31 positive cervical samples of Hungarian women. A phylogenetic tree constructed from the nucleotide sequences of the LCR variants revealed the presence of three intratypic variant lineages of HPV 31, in accordance with previous results. In order to explore the functional consequences of sequence variation in the LCR of HPV 31, selected LCR variants were cloned into a luciferase reporter vector, transfected into C33-A cells and tested in luciferase reporter assays. Significant differences were found between the transcriptional activities of HPV 31 LCR variants belonging to different variant lineages. As the LCR is governing the transcription of the E6 and E7 oncogenes, the differences in the transcriptional activities of LCR variants may be associated with differences in their oncogenic potential.

Genital human papillomaviruses among women of reproductive age in Jamaica

To characterize the prevalence and distribution of genital human papillomavirus (HPV) types among women in Jamaica, and to explore risk factors associated with HPV infection. This was a cross-sectional study that took place in April-July 2010 with 852 sexually-active women, 16-49 years of age, who had attended a selected public or private primary health clinic in one of Jamaica's four health authority regions. Sociodemographic data was collected from each participant by trained study staff. Each participant had a gynecological examination that included a clinical Pap test and a cervical sample for HPV detection and typing-performed using the Research Use Only Linear Array (LA) genotyping assay (Roche Diagnostics Corp., Indianapolis, Indiana, United States). Overall and type-specific prevalence of HPV infection was calculated for 37 HPV types included in the LA genotyping assay. HPV DNA was detected in 460 of the 852 women (54.0%). Oncogenic HPV was detected in 297 women (34.9%) and HPV types 16/18 were found in 86 women (10.1%). The most frequently occurring HPV types were: 16 (6.2%); 35 (6.0%); 62 and 83 (5.5%); 61 and 58 (5.4%); 84 (4.7%); 18 (4.3%); and, 66 and 81 (4.2%). HPV prevalence was highest among women who were single, young (16-19 years), and had had more than three sexual partners in their lifetime. These results, coupled with high rates of cervical cancer, support introducing HPV vaccines while maintaining and strengthening cervical cancer screening services. Policy decision-making that reflects these results is instrumental to establishing a comprehensive cervical cancer program in Jamaica.