Search

Background: Sinonasal exophytic papillomas (SNEP) are benign tumours arising from nasal mucosa. Human papillomavirus (HPV) infection seems to be related to the aetiology of a fraction of SNEP cases. SNEP presentation can be focal (FSNEP) or diffuse (DSNEP), but factors related to focal or diffuse presentation have not yet been well ascertained. This study aimed to analyse clinical, histological, and HPV-related differences between FSNEP and DSNEP. Methods: A retrospective cohort of 18 patients with SNEP from our centre were evaluated. Demographic, clinical and follow-up data were collected. All samples were subject to histopathological evaluation, DNA quality control, HPV-DNA detection, and viral load assessment. Univariate analyses were performed to evaluate differences between FSNEP and DSNEP. Results: Twelve SNEP patients were included in the final analysis. Seven patients had a diffuse nasal presentation, being younger than patients affected with FSNEP (42.7 years vs. 65.2 years, p = 0.019). The nasal septum was significantly more affected in DSNEP than in FSNEP (85.7% vs. 20%, p = 0.029). HPV-DNA was detected more frequently (100%) in DSNEP (HPV11 in six cases, HPV6 in one case) than in FSNEP (40%, p = 0.045, HPV6 in two cases). The median viral load among HPV6-positive samples was 626.8 virus/cell for FSNEP and 80.2 for DSNEP, and among HPV11-positive samples was 1673.7 for DSNEP. Recurrences were more frequent in the diffuse than in the focal group (85.7% vs. 20%, p = 0.029). Conclusions: The diffuse presentation of SNEP seems to be related to younger patients, nasal septum involvement, HPV infection, mostly HPV11, and a higher risk of recurrence. [ABSTRACT FROM AUTHOR]

Recent studies have revealed the impact of human papillomavirus (HPV) infections on the cervicovaginal microbiome; however, few have explored the utility of self-collected specimens (SCS) for microbiome detection, obtained using standardised methods for HPV testing. Here, we present a proof-of-concept analysis utilising Oxford Nanopore sequencing of the 16S rRNA gene in paired samples collected either by the patient using an Evalyn Brush or collected by a physician using liquid-based cytology (LBC). We found no significant differences in the α-diversity estimates between the SCS and LBC samples. Similarly, when analysing β-diversity, we observed a close grouping of paired samples, indicating that both collection methods detected the same microbiome features. The identification of genera and Lactobacillus species in each sample allowed for their classification into community state types (CSTs). Notably, paired samples had the same CST, while HPV-positive and -negative samples belonged to distinct CSTs. As previously described in other studies, HPV-positive samples exhibited heightened bacterial diversity, reduced Lactobacillus abundance, and an increase in genera like Sneathia or Dialister. Altogether, this study showed comparable results between the SCS and LBC samples, underscoring the potential of self-sampling for analysing the microbiome composition in cervicovaginal samples initially collected for HPV testing in the context of cervical cancer screening. [ABSTRACT FROM AUTHOR]

Human Papillomavirus (HPV) prophylactic vaccination has proven effective in preventing new infections, but it does not treat existing HPV infections or associated diseases. Hence, there is still an important reservoir of HPV in adults, as vaccination programs are mainly focused on young women. The primary objective of this non-randomized, open-label trial is to evaluate if a 3-dose regimen of Gardasil-9 in HPV16/18-positive women could reduce the infective capacity of their body fluids. We aim to assess if vaccine-induced antibodies could neutralize virions present in the mucosa, thus preventing the release of infective particles and HPV transmission to sexual partners. As our main endpoint, the E1^E4-HaCaT model will be used to assess the infectivity rate of cervical, anal and oral samples, obtained from women before and after vaccination. HPV DNA positivity, virion production, seroconversion, and the presence of antibodies in the exudates, will be evaluated to attribute infectivity reduction to vaccination. Our study will recruit two different cohorts (RIFT-HPV1 and RIFT-HPV2) of non-vaccinated adult women. RIFT-HPV1 will include subjects with an HPV16/18 positive cervical test and no apparent cervical lesions or cervical lesions eligible for conservative treatment. RIFT-HPV2 will include subjects with an HPV16/18 positive anal test and no apparent anal lesions or anal lesions eligible for conservative treatment, as well as women with an HPV16/18 positive cervical test and HPV-associated vulvar lesions. Subjects complying with inclusion criteria for both cohorts will be recruited to the main cohort, RIFT-HPV1. Three doses of Gardasil-9 will be administered intramuscularly at visit 1 (0 months), visit 2 (2 months) and visit 3 (6 months). Even though prophylactic HPV vaccines would not eliminate a pre-existing infection, our results will determine if HPV vaccination could be considered as a new complementary strategy to prevent HPV-associated diseases by reducing viral spread. Trial registration: https://clinicaltrials.gov/ct2/show/NCT05334706. [ABSTRACT FROM AUTHOR]

Elevated rates of human papillomavirus (HPV)-related anal high-grade squamous intraepithelial lesions (HSIL) and anal cancer (AC) in populations like men who have sex with men (MSM) living with HIV underscore the need for effective screening. While high-resolution anoscopy-guided biopsy is the gold standard, limited provider availability poses a challenge. This has spurred interest in identifying biomarkers for improved AC prevention. Antibodies against HPV16 oncoprotein E6, known as markers for cervical and oropharyngeal cancers, are the focus of the current study. The systematic review and meta-analysis included six studies meeting inclusion criteria, assessing HPV16 E6 seroprevalence in individuals with anal HSIL or AC. A two-step meta-analysis estimated pooled odds ratios and 95% confidence intervals (CI) for HPV16 E6 seroprevalence and HSIL or AC. Pooled prevalence, sensitivity, specificity, and diagnostic odds ratios were also calculated. This meta-analysis revealed a 3.6-fold increased risk of HSIL for HPV16 E6 seropositive individuals, escalating to a 26.1-fold risk increase for AC. Pooled specificity and sensitivity indicated a high specificity (0.99; 95%CI: 0.99, 0.99) but lower sensitivity (0.19; 95%CI: 0.10, 0.34) for HPV16 E6 serostatus as an AC biomarker. In conclusion, while HPV16 E6 seroprevalence demonstrates specificity as a potential biomarker for HPV-related AC, its utility as a standalone screening tool may be limited. Instead, it could serve effectively as a confirmation test, particularly in high-risk populations, alongside other diagnostic methods. Further research is imperative to explore HPV16 E6 seroconversion dynamics and alternative screening algorithms. [ABSTRACT FROM AUTHOR]

A growing proportion of head and neck cancer (HNC), especially oropharyngeal cancer (OPC), is caused by human papillomavirus (HPV). There are several markers for HPV‐driven HNC, one being HPV early antigen serology. We aimed to investigate the diagnostic accuracy of HPV serology and its performance across patient characteristics. Data from the VOYAGER consortium was used, which comprises five studies on HNC from North America and Europe. Diagnostic accuracy, that is, sensitivity, specificity, Cohen's kappa and correctly classified proportions of HPV16 E6 serology, was assessed for OPC and other HNC using p16INK4a immunohistochemistry (p16), HPV in situ hybridization (ISH) and HPV PCR as reference methods. Stratified analyses were performed for variables including age, sex, smoking and alcohol use, to test the robustness of diagnostic accuracy. A risk‐factor analysis based on serology was conducted, comparing HPV‐driven to non‐HPV‐driven OPC. Overall, HPV serology had a sensitivity of 86.8% (95% CI 85.1‐88.3) and specificity of 91.2% (95% CI 88.6‐93.4) for HPV‐driven OPC using p16 as a reference method. In stratified analyses, diagnostic accuracy remained consistent across sex and different age groups. Sensitivity was lower for heavy smokers (77.7%), OPC without lymph node involvement (74.4%) and the ARCAGE study (66.7%), while specificity decreased for cases with <10 pack‐years (72.1%). The risk‐factor model included study, year of diagnosis, age, sex, BMI, alcohol use, pack‐years, TNM‐T and TNM‐N stage. HPV serology is a robust biomarker for HPV‐driven OPC, and its diagnostic accuracy is independent of age and sex. Future research is suggested on the influence of smoking on HPV antibody levels. [ABSTRACT FROM AUTHOR]

Simple Summary: The utility of a diagnostic algorithm for the detection of HPV-driven oral cavity (OCC), oropharyngeal (OPC), and laryngeal (LC) carcinomas using HPV-DNA testing followed by p16INK4a immunohistochemistry, taking E6*I mRNA detection as the reference standard, was assessed in HPV-DNA-positive formalin-fixed paraffin-embedded samples from 29 countries. The concordance of p16INK4a and E6*I mRNA among 78, 257, and 51 HPV-DNA-positive OCC, OPC, and LC, respectively, was moderate to substantial in OCC and OPC but only fair in LC. A different p16INK4a expression pattern was observed in those cases HPV-DNA-positive for types other than HPV16, as compared to HPV16-positive cases. We concluded that the diagnostic algorithm of HPV-DNA testing followed by p16INK4a immunohistochemistry might be helpful in the diagnosis of HPV-driven OCC and OPC, but not LC. Our study provides new insights into the use HPV-DNA, p16INK4a, and HPV-E6*I mRNA for diagnosing an HPV-driven head and neck carcinoma. Background: Tests or test algorithms for diagnosing HPV-driven oral cavity and laryngeal head and neck carcinomas (HNC) have not been yet validated, and the differences among oral cavity and laryngeal sites have not been comprehensively evaluated. We aimed to assess the utility of a diagnostic algorithm for the detection of HPV-driven oral cavity (OCC), oropharyngeal (OPC) and laryngeal (LC) carcinomas using HPV-DNA testing followed by p16INK4a immunohistochemistry, taking E6*I mRNA detection as the reference standard. Methods: Formalin-fixed paraffin-embedded OCC, OPC, and LC carcinomas were collected from pathology archives in 29 countries. All samples were subjected to histopathological evaluation, DNA quality control, and HPV-DNA detection. All HPV-DNA-positive samples (including 78 OCC, 257 OPC, and 51 LC out of 3680 HNC with valid HPV-DNA results) were also tested for p16INK4a immunohistochemistry and E6*I mRNA. Three different cutoffs of nuclear and cytoplasmic staining were evaluated for p16INK4a: (a) >25%, (b) >50%, and (c) ≥70%. The concordance of p16INK4a and E6*I mRNA among HPV-DNA-positive OCC, OPC, and LC cases was assessed. Results: A total of 78 OCC, 257 OPC, and 51 LC were HPV-DNA-positive and further tested for p16INK4a and E6*I mRNA. The percentage of concordance between p16INK4a (cutoff ≥ 70%) and E6*I mRNA among HPV-DNA-positive OCC, OPC, and LC cases was 79.5% (95% CI 69.9–89.1%), 82.1% (95% CI 77.2–87.0%), and 56.9% (95% CI 42.3–71.4%), respectively. A p16INK4a cutoff of >50% improved the concordance although the improvement was not statistically significant. For most anatomical locations and p16INK4a cutoffs, the percentage of discordant cases was higher for HPV16- than HPV-non16-positive cases. Conclusions: The diagnostic algorithm of HPV-DNA testing followed by p16INK4a immunohistochemistry might be helpful in the diagnosis of HPV-driven OCC and OPC, but not LC. A different p16INK4a expression pattern was observed in those cases HPV-DNA-positive for types other than HPV16, as compared to HPV16-positive cases. Our study provides new insights into the use HPV-DNA, p16INK4a, and HPV-E6*I mRNA for diagnosing an HPV-driven HNC, including the optimal HPV test or p16INK4a cutoffs to be used. More studies are warranted to clarify the role of p16INK4a and HPV status in both OPC and non-OPC HNC. [ABSTRACT FROM AUTHOR]

Copyright of Revista Española de Quimioterapia is the property of Sociedad Espanola de Quimioterapia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: HIV‐positive men who have sex with men (MSM) are a vulnerable group for anal cancer (AC), a cancer with a well‐described precursor lesion, which can be detected early in screening programs using anal liquid‐based cytology (aLBC). We aim to compare two aLBC sample collection devices: cytology brush (CB) and Dacron swab (DS). Methods: Retrospective analysis of two consecutive study periods, the first using CB and the second DS. Participants underwent an aLBC, a human papillomavirus (HPV) DNA test and a high‐resolution anoscopy (HRA), and a biopsy was performed for suspicious lesions. The sensitivity and specificity of aLBC, area under the receiver operating characteristic (ROC) curve (AUC), and concordance between cytology and HRA were assessed using Cohen's kappa coefficient. Results: A total of 239 participants were enrolled (CB group, 120; DS group, 119). aLBC was benign in 46% of samples, and high‐grade squamous intraepithelial lesion (HSIL) was detected in 11.7%. Prevalence of biopsy‐proven HSIL was 15.3%. No differences in cytological and histological results were observed between the groups. aLBC‐HRA concordance was weak for benign results (CB group, k = 0.309; DS group, k = 0.350) as well as for HSIL (k = 0.321 and 0.387, respectively). Sensitivity and specificity were 100% and 51.4%, respectively, in the CB group and 88% and 54.3% in the DS group (AUC = 0.711 and 0.759, respectively, P‐value =.514). Representation of the transformation zone (TZ) was adequate in 83.3% of samples in the CB group and 50.4% in the DS group (P‐value <.001). Conclusion: Our data suggest that both devices had similar accuracy to detect anal HSIL, although samples collected with CB are more likely to have an adequate TZ representation, the presence of which could be an indicator of sample quality. This article aims to compare two anal cytology sample collection devices for anal cancer screening in HIV‐positive men who have sex with men: cytology brush and Dacron swab. The results suggest that both devices have similar accuracy to detect anal HSIL, although samples collected with CB are more likely to have an adequate TZ representation. [ABSTRACT FROM AUTHOR]

Abstract Background Information on human papillomavirus (HPV) type distribution is necessary to evaluate the potential impact of current and future HPV vaccines. We estimated the relative contribution (RC) to invasive cervical cancer (ICC) and precancerous cervical lesions of the nine HPV types (HPV 6/11/16/18/31/33/45/52/58) included in an HPV vaccine currently under development. Methods Estimations on ICC were based on an international study of 8,977 HPV positive cases and estimations on precancerous cervical lesions were extracted from a published meta-analysis including 115,789 HPV positive women. Globocan 2008 and 2010 World Population Prospects were used to estimate current and future projections of new ICC cases. Results RC of the 9 HPV types in ICC was 89.4%, with 18.5% of cases positive for HPV 31/33/45/52/58. Regional variations were observed. RCs varied by histology, ranging between 89.1% in squamous cell carcinomas (SCC) and 95.5% in adenocarcinomas (ADC). HPV 16/18/45 were detected in 94.2% of ADC. RC of the 9 types altogether decreased with age (trend test p The RCs of individual high risk HPV types varied by cytological and histological grades of HPV-positive precancerous cervical lesions, and there was an under representation of HPV 18 and 45 compared to ICC. Conclusions The addition of HPV 31/33/45/52/58 to HPV types included in current vaccines could prevent almost 90% of ICC cases worldwide. If the nine-valent vaccine achieves the same degree of efficacy than previous vaccines, world incidence rates could be substantially reduced.

International surveys find HPV‐negativity in up to 30% of cervical adenocarcinomas. We investigated the pathological diagnosis by expert consensus with immunohistochemistry and the presence of somatic mutations in recognised tumour genes in HPV‐positive and negative cervical adenocarcinomas (CADC). A sample was selected of 45 paraffin‐embedded cervical blocks diagnosed locally as usual cervical adenocarcinoma from a global study. These represented different diagnoses made at previous diagnostic review and HPV status. All were suitable for analysis for somatic tumour associated gene mutations. Three pathologists examined H/E slides and immunohistochemistry for p16, progesterone receptor and p53 and classified the cases. L1 genes from high‐risk HPVs and low‐risk HPVs were analysed by SPF10 PCR‐DEIA‐LiPA25 version 1 in whole tissue sections and microdissected tumour and retested by PCR for E6/E7 genes of hrHPVs if negative. Cases were analysed for microsatellite instability and next‐generation sequencing mutation analysis. From the 45 cases, 20 cases of usual CADC were confirmed of which 17 (85%) were HPV‐positive in tumour cells. The other 25 cases were reclassified as endometrial, serous, clear‐cell and gastric‐type adenocarcinomas and all were HPV‐negative in tumour cells. Careful retesting for HPV DNA and IHC leads to more accurate identification of HPV‐positive usual cervical adenocarcinomas. Endometrioid endometrial adenocarcinomas, other uterine adenocarcinoma with multiple somatic mutations were important in misclassification of HPV‐negative cases locally managed as cervical adenocarcinoma, as was gastric‐type adenocarcinoma with germline STK11 mutation in East Asia. Few consensuses confirmed HPV‐negative usual cervical adenocarcinomas showed somatic tumorigenic mutations also seen in some HPV‐positive usual CADC. What's new? As many as 30 percent of cervical adenocarcinomas initially test negative for human papillomavirus (HPV), which is necessary but not sufficient for the development of cervical cancer. Here, the authors carried out an extensive survey of different categories of adenocarcinoma initially diagnosed and managed as cervical adenocarcinoma. Analyses show that misdiagnosis of endometrioid endometrial cancer and serous or clear cell cancers as cervical adenocarcinoma are not infrequent and that HPV‐negative cervical adenocarcinoma is a real, though infrequent diagnosis. The findings highlight issues of misdiagnosis and the role of somatic or germ‐line mutations in tumor genes in cervical adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) is the cause of a fraction of head and neck squamous cell carcinoma. Although this relation is well-known, it is still not clear the role of HPV in premalignant oral lesions such as oral lichen planus (OLP) and dysplasia. We aimed to evaluate the HPV-DNA prevalence and type distribution in a set of oral biopsies obtained from patients diagnosed with OLP and dysplasia, as well as the role of HPV in these lesions. Methods: A retrospective cohort of all premalignant oral lesions consecutively diagnosed from March 30th 1995 to May 21st 2014 at Hospital of Bellvitge and Odontological University Hospital of Bellvitge was identified and classified in four groups: OLP (groups 1 and 2) and dysplasias (groups 3 and 4) that progressed or not to invasive cancer during follow-up. A random selection targeting 25 cases was aimed to be performed for each group. All selected cases were subjected to pathological evaluation, DNA quality control and HPV-DNA detection. HPV-DNA positive samples were further subject to p16INK4a analysis. Results: A total of 83 cases yielded a valid HPV-DNA result. From those, 7 and 34 cases were OLP that progressed or not to invasive cancer during follow-up, whereas 24 and 18 cases were displasias that progressed or not to invasive cancer during follow-up, respectively. HPV-DNA was detected in 4 samples (3 dysplastic lesions and 1 OLP). Two samples were HPV16 positive (2%), 1 sample HPV18 positive (1%) and 1 sample (1%) was HPV indeterminate. Two out of four HPV-DNA positive cases had high p16INK4a expression and none of the HPV positive cases progressed to invasive cancer during long-term follow-up. Conclusions: We found a low HPV-DNA attributable fraction in premalignant lesions of the oral cavity, suggesting that HPV is unlikely to play a significant role in oral carcinogenesis in our setting. [ABSTRACT FROM AUTHOR]

Background: Given the different nature and better outcomes of oropharyngeal carcinoma (OPC) associated with human papillomavirus (HPV) infection, a novel clinical stage classification for HPV-related OPC has been accepted for the 8th edition AJCC TNM (ICON-S model). However, it is still unclear the HPV-relatedness definition with best diagnostic accuracy and prognostic value. Material and methods: The aim of this study was to compare different staging system models proposed for HPV-related OPC patients: 7th edition AJCC TNM, RPA stage with non-anatomic factors (Princess Margaret), RPA with N categories for nasopharyngeal cancer (MD-Anderson) and AHR-new (ICON-S), according to different HPV-relatedness definitions: HPV-DNA detection plus an additional positive marker (p16INK4a or HPV-mRNA), p16INK4a positivity alone or the combination of HPV-DNA/p16INK4a positivity as diagnostic tests. Results: A total of 788 consecutive OPC cases diagnosed from 1991 to 2013 were considered eligible for the analysis. Of these samples, 66 (8.4%) were positive for HPV-DNA and (p16INK4a or HPV-mRNA), 83 (10.5%) were p16INK4a positive and 58 (7.4%) were double positive for HPV-DNA/p16INK4a. ICON-S model was the staging system, which performed better in our series when using at least two biomarkers to define HPV-causality. When the same analysis was performed considering only p16INK4a-positivity, RPA stage with non-anatomic factors (Princess Margaret) has the best classification based on AIC criteria. Conclusion: HPV-relatedness definition for classifying HPV-related OPC patient do impact on TNM classification and patients’ survival. Further studies assessing HPV-relatedness definitions are warranted to better classify HPV-related OPC patients in the era of de-escalation clinical trials. [ABSTRACT FROM AUTHOR]

The main etiological factor of precancerous lesion and invasive cervical cancer are oncogenic human papillomaviruses types (HPVs). The objective of this study was to establish the distribution of the most common HPVs in different cervical lesions and cancer prior to the implementation of organized population-based cervical screening and HPV vaccination in Croatia. In this study, 4,432 cervical specimens, collected through a 16-year period, were tested for the presence of HPV-DNA by polymerase chain reaction (PCR) with three sets of broad-spectrum primers and type-specific primers for most common low-risk (LR) types (HPV-6, 11) and the most common high-risk (HR) types (HPV-16, 18, 31, 33, 45, 52, 58). Additional 35 archival formalin-fixed, paraffin embedded tissue of cervical cancer specimens were analyzed using LiPA25 assay. The highest age-specific HPV-prevalence was in the group 18–24 years, which decreased continuously with age (P<0.0001) regardless of the cytological diagnosis. The prevalence of HR-HPV types significantly increased (P<0.0001) with the severity of cervical lesions. HPV-16 was the most common type found with a prevalence (with or without another HPV-type) of 6.9% in normal cytology, 15.5% in atypical squamous cells of undetermined significance, 14.4% in low-grade squamous intraepithelial lesions, 33.3% in high-grade squamous intraepithelial lesions, and 60.9% in cervical cancer specimens (P<0.0001). This study provides comprehensive and extensive data on the distribution of the most common HPV types among Croatian women, which will enable to predict and to monitor the impact of HPV-vaccination and to design effective screening strategies in Croatia. [ABSTRACT FROM AUTHOR]

Background: In addition to cervical cancer, human papillomavirus (HPV) is responsible for a significant proportion of cancers and precancerous lesions of the vulva, vagina, anus, penis, head and neck, as well as genital warts. We estimated the annual number of new cases of these diseases attributable to 9-valent HPV vaccine types in women and men in Europe. Methods: The annual number of new cancers of the cervix, vulva, vagina, anus, penis, and selected head and neck sites in the population of the European Medicines Agency territory was estimated based on age-specific incidence rates extracted from Cancer Incidence in 5 Continents, Volume X and Eurostat population data for 2015. The annual number of new cancers attributable to 9-valent HPV vaccine types was estimated by applying the HPV attributable fraction from reference publications based on a large European multicenter study. For non-cervical cancers, HPV attributable fractions were based on oncogenically-active HPV infections only (i.e., detection of HPV DNA and either mRNA and/or p16 positivity). For precancerous lesions of the cervix, vulva, vagina, and anus, and for genital warts, previously published estimations were updated for the 2015 population. Results: The annual number of new cancers attributable to 9-valent HPV vaccine types was estimated at 47,992 (95% bound: 39,785-58,511). Cervical cancer showed the highest burden (31,130 cases), followed by head and neck cancer (6,786 cases), anal cancer (6,137 cases), vulvar cancer (1,466 cases), vaginal cancer (1,360 cases), and penile cancer (1,113 cases). About 81% were estimated to occur in women and 19% in men. The annual number of new precancerous lesions (CIN2+, VIN2/3, VaIN2/3, and AIN2/3) and genital warts attributable to 9-valent HPV vaccine types was estimated at 232,103 to 442,347 and 680,344 to 844,391, respectively. Conclusions: The burden of cancers associated with 9-valent HPV vaccine types in Europe is substantial in both sexes. Head and neck cancers constitute a heavy burden, particularly in men. Overall, about 90% of HPV-related cancers, 80% of precancerous lesions, and 90% of genital warts are expected to be attributable to 9-valent HPV vaccine types each year, demonstrating the important preventive potential of the 9-valent HPV vaccine in Europe. [ABSTRACT FROM AUTHOR]

Few studies have assessed the burden of human papillomavirus (HPV) infection in Pakistan. We aim to provide specific information on HPV-type distribution in invasive cervical cancer (ICC) in the country. A total of 280 formalin-fixed paraffin-embedded tissue blocks were consecutively selected from Shaukat Khanum Memorial Cancer Hospital and Research Centre (Lahore, Pakistan). HPV-DNA was detected by SPF10 broad-spectrum PCR followed by DNA enzyme immunoassay and genotyping by LiPA25. HPV-DNA prevalence was 87.5% (95%CI: 83.0-91.1), with 96.1% of cases histologically classified as squamous cell carcinoma. Most of the HPV-DNA positive cases presented single infections (95.9%). HPV16 was the most common type followed by HPV18 and 45. Among HPV-DNA positive, a significantly higher contribution of HPV16/18 was detected in Pakistan (78.4%; 72.7-83.3), compared to Asia (71.6%; 69.9-73.4) and worldwide (70.8%; 69.9-71.8) and a lower contribution of HPVs31/33/45/52/58 (11.1%; 7.9-15.7 vs. 19.8%; 18.3-21.3 and 18.5%; 17.7-19.3). HPV18 or HPV45 positive ICC cases were significantly younger than cases infected by HPV16 (mean age: 43.3, 44.4, 50.5 years, respectively). A routine cervical cancer screening and HPV vaccination program does not yet exist in Pakistan; however, the country could benefit from national integrated efforts for cervical cancer prevention and control. Calculated estimations based on our results show that current HPV vaccine could potentially prevent new ICC cases. [ABSTRACT FROM AUTHOR]

Background Invasive penile cancer is a rare disease with an approximately 22 000 cases per year. The incidence is higher in less developed countries, where penile cancer can account for up to 10% of cancers among men in some parts of Africa, South America, and Asia. Objective To describe the human papillomavirus (HPV) DNA prevalence, HPV type distribution, and detection of markers of viral activity (ie, E6*I mRNA and p16 INK4a ) in a series of invasive penile cancers and penile high-grade squamous intraepithelial lesions (HGSILs) from 25 countries. A total of 85 penile HGSILs and 1010 penile invasive cancers diagnosed from 1983 to 2011 were included. Design, setting, and participants After histopathologic evaluation of formalin-fixed paraffin-embedded samples, HPV DNA detection and genotyping were performed using the SPF-10/DEIA/LiPA 25 system, v.1 (Laboratory Biomedical Products, Rijswijk, The Netherlands). HPV DNA–positive cases were additionally tested for oncogene E6*I mRNA and all cases for p16 INK4a expression, a surrogate marker of oncogenic HPV activity. Outcome measurements and statistical analysis HPV DNA prevalence and type distributions were estimated. Results and limitations HPV DNA was detected in 33.1% of penile cancers (95% confidence interval [CI], 30.2–36.1) and in 87.1% of HGSILs (95% CI, 78.0–93.4). The warty-basaloid histologic subtype showed the highest HPV DNA prevalence. Among cancers, statistically significant differences in prevalence were observed only by geographic region and not by period or by age at diagnosis. HPV16 was the most frequent HPV type detected in both HPV-positive cancers (68.7%) and HGSILs (79.6%). HPV6 was the second most common type in invasive cancers (3.7%). The p16 INK4a upregulation and mRNA detection in addition to HPV DNA positivity were observed in 69.3% of HGSILs, and at least one of these HPV activity markers was detected in 85.3% of cases. In penile cancers, these figures were 22.0% and 27.1%, respectively. Conclusions About a third to a fourth of penile cancers were related to HPV when considering HPV DNA detection alone or adding an HPV activity marker, respectively. The observed HPV type distribution reinforces the potential benefit of current and new HPV vaccines in the reduction of HPV-related penile neoplastic lesions. Patient summary About one-third to one-quarter of penile cancers were related to human papillomavirus (HPV). The observed HPV type distribution reinforces the potential benefit of current and new HPV vaccines to prevent HPV-related penile neoplastic lesions. [ABSTRACT FROM AUTHOR]

Background: We estimated the potential impact of an investigational 9-valent human papillomavirus (HPV) vaccine (HPVs 6/11/16/18/31/33/45/52/58) in HPV-related cervical disease in Brazil, Mexico, India and China, to help to formulate recommendations on cervical cancer prevention and control. Methods: Estimations for invasive cervical cancer (ICC) were based on an international study including 1356 HPV-positive cases for the four countries altogether, and estimations for precancerous cervical lesions were extracted from a published meta-analysis including 6025 HPV-positive women from the four mentioned countries. Globocan 2012 and 2012 World Population Prospects were used to estimate current and future projections of new ICC cases. Results: Combined proportions of the 9 HPV types in ICC were 88.6% (95%CI: 85.2-91.3) in Brazil, 85.7% (82.3-88.8) in Mexico, 92.2% (87.9-95.3) in India and 97.3% (93.9-99.1) in China. The additional HPV 31/33/ 45/52/58 proportions were 18.8% (15.3-22.7) in Brazil, 17.6% (14.2-21.2) in Mexico, 11.3% (7.5-16.1) in India and 11.9% (7.5-17.2) in China. HPV6 and 11 single types were not identified in any of the samples. Proportion of the individual 7 high risk HPV types included in the vaccine varied by cytological and histological grades of HPV-positive precancerous cervical lesions. HPV 16 was the dominant type in all lesions, with contributions in low grade lesions ranging from 16.6%(14.3-19.2) in Mexico to 39.8% (30.0-50.2) in India, and contributions in high grade lesions ranging from 43.8% (36.3-51.4) in Mexico to 64.1% (60.6-67.5) in Brazil. After HPV 16, variations in other majors HPV types were observed by country, with an under representation of HPV 18 and 45 compared to ICC. Conclusion: The addition of HPVs 31/33/45/52/58 to HPV types included in current vaccines could increase the ICC preventable fraction in a range of 12 to 19% across the four countries, accounting the 9-types altogether 90% of ICC cases. Assuming the same degree of efficacy of current vaccines, the implementation of the 9-valent HPV vaccine in Brazil, Mexico, India and China would substantially impact on the reduction of the world cervical cancer burden. [ABSTRACT FROM AUTHOR]

Contribution over time of human papillomavirus (HPV) types in human cancers has been poorly documented. Such data is fundamental to measure current HPV vaccines impact in the years to come. We estimated the HPV type-specific distribution in a large international series of invasive cervical cancer (ICC) over 70 years prior to vaccination. Paraffin embedded ICC cases diagnosed between 1940 and 2007 were retrieved from eleven countries in Central-South America, Asia and Europe. Included countries reported to have low-medium cervical cancer screening uptake. Information on age at and year of diagnosis was collected from medical records. After histological confirmation, HPV DNA detection was performed by SPF-10/DEIA/LiPA25 (version1). Logistic regression models were used for estimating the adjusted relative contributions (RC) of HPV16 and of HPV18 over time. Among 4,771 HPV DNA positive ICC cases, HPV16 and HPV18 were the two most common HPVs in all the decades with no statistically significant variations of their adjusted-RC from 1940-59 to 2000-07 (HPV16-from 61.5 to 62.1%, and HPV18-from 6.9 to 7.2%). As well, the RC of other HPV types did not varied over time. In the stratified analysis by histology, HPV16 adjusted-RC significantly increased across decades in adenocarcinomas. Regarding age, cases associated to either HPV16, 18 or 45 were younger than those with other HPV types in all the evaluated decades. The observed stability on the HPV type distribution predicts a high and stable impact of HPV vaccination in reducing the cervical cancer burden in future vaccinated generations. [ABSTRACT FROM AUTHOR]

Background: Exploring the presence and role of human papillomavirus (HPV) in head and neck cancer (HNC) is a necessary step to evaluate the potential impact of HPV prophylactic vaccines. Objective: To assess the prevalence and oncogenic role of HPV in HNC in Senegal. Methods: This is a multicenter cross-sectional study. Paraffin-embedded blocks of cases diagnosed with invasive HNC between 2002 and 2010 were collected from 4 pathology laboratories in Senegal. Presence of HPV DNA was determined by PCR and DEIA, and genotyping performed with LiPA25. Tubulin analysis was performed to assess DNA quality. HPV DNA-positive cases were tested for p16INK4a expression. Findings: A total of 117 cases were included in the analysis: 71% were men, mean age was 52 years old (SD ±18.3), and 96% of cases were squamous cell carcinoma. Analysis was performed on 41 oral cavity tumors, 64 laryngeal tumors, 5 oropharyngeal tumors and 7 pharyngeal tumors. Only four cases (3.4%; 95% CI = 0.9%-8.5%) harbored HPV DNA. HPV types detected were HPV16, HPV35 and HPV45. However, among HPV-positive cases, none showed p16INK4a overexpression. Conclusion: Our findings indicate that HPV DNA prevalence in HNC in Senegal is very low, suggesting that HPV is not a strong risk factor for these cancers. Additional larger studies are needed to confirm these findings and explore other potential risk factors specific to the region. [ABSTRACT FROM AUTHOR]

Objectives To describe human papillomavirus (HPV) distribution in invasive cervical carcinoma (ICC) from Mali and Senegal and to compare type-specific relative contribution among sub-Saharan African (SSA) countries. Methods A multicentric study was conducted to collect paraffin-embedded blocks of ICC. Polymerase chain reaction, DNA enzyme immunoassay and line probe assay were performed for HPV detection and genotyping. Data from SSA (Mozambique, Nigeria and Uganda) and 35 other countries were compared. Results One hundred and sixty-four ICC cases from Mali and Senegal were tested from which 138 were positive (adjusted prevalence = 86.8%; 95% CI = 79.7-91.7%). HPV16 and HPV18 accounted for 57.2% of infections and HPV45 for 16.7%. In SSA countries, HPV16 was less frequent than in the rest of the world (49.4% vs. 62.6%; P < 0.0001) but HPV18 and HPV45 were two times more frequent (19.3% vs. 9.4%; P < 0.0001 and 10.3% vs. 5.6%; P < 0.0001, respectively). There was an ecological correlation between HIV prevalence and the increase of HPV18 and the decrease of HPV45 in ICC in SSA ( P = 0.037 for both). Conclusion HPV16/18/45 accounted for two-thirds of the HPV types found in invasive cervical cancer in Mali and Senegal. Our results suggest that HIV may play a role in the underlying HPV18 and HPV45 contribution to cervical cancer, but further studies are needed to confirm this correlation. [ABSTRACT FROM AUTHOR]

Countries are now challenged by the rapid development of vaccines aimined at the primary prevention of infections. In the years to come, several vaccines will need to be considered as potential candidates in routine immunization programs. Recently, two new vaccines against two/four types of human papillomavirus (HPV) have been commercialized. Bivalent HPV 16 and 18 (Cervarix™) and quadrivalent HPV 6, 11, 16 and 18 (Gardasil®) vaccines are now extensively used in some countries. These vaccines will prevent infection and long-running complications, such as cervical cancer, other HPV-related cancers and genital warts (for the quadrivalent vaccine). The beneficial effect of these vaccines will be largely observed in women. This article summarizes the burden of HPV preventable disease worldwide and briefly describes the impact of secondary prevention and the most relevant aspects of the current available vaccines, their efficacy and safety. Finally, some major aspects that are likely to impact the introduction of these vaccines around the world are outlined, with particular emphasis on developing countries. [ABSTRACT FROM AUTHOR]

Background Many countries, mainly high- and upper-middle income, have implemented human papillomavirus (HPV) vaccination programs, with 47 million women receiving the full course of vaccine (three doses) in 2014. To evaluate the potential impact of HPV vaccines in the reduction of HPV-related disease, we aimed to estimate the HPV type distribution and burden of anogenital and head and neck cancers attributable to HPV types (HPVs 16/18/31/33/45/52/58/6/11) included in currently licensed HPV vaccines. Methods In all, 18 247 formalin-fixed paraffin-embedded specimens were retrieved from 50 countries. HPV DNA detection and typing were performed with the SPF-10 PCR/DEIA/LiPA25 system. With the exception of cervical cancer, HPV DNA-positive samples were additionally subjected to HPV E6*I mRNA detection and/or p16INK4a immunohistochemistry. For cervical cancer, estimates were based on HPV DNA, whereas for other sites, estimates were based on HPV DNA, E6*I mRNA, and p16INK4a biomarkers. Results The addition of HPVs 31/33/45/52/58 to HPVs 16/18/6/11 in the nonavalent HPV vaccine could prevent almost 90% of cervical cancer cases worldwide. For other sites, the nonavalent HPV vaccine could prevent 22.8% of vulvar, 24.5% of penile, 60.7% of vaginal, 79.0% of anal cancers, 21.3% of oropharyngeal, 4.0% of oral cavity, and 2.7% of laryngeal cancer cases. Conclusions Our estimations suggest a potential impact of the nonavalent HPV vaccine in reducing around 90% of cervical cancer cases and a global reduction of 50% of all the cases at HPV-related cancer sites. [ABSTRACT FROM AUTHOR]

Squamous cell carcinomas with two or more coexisting clearly different histological subtypes of penile carcinomas are designated as mixed carcinomas in current classification models. They represent about 10% of all penile carcinomas. The aim of this study was to detect HPV genotypes in these unusual tumors. Tumors were selected from an international series of 1010 patients with penile carcinomas. Mixed carcinomas were grouped, according to WHO recommendations, as follows: 1. Carcinomas with warty/basaloid features mixed with HPV-independent carcinomas and 2. HPV-independent subtypes mixed with each other. HPV detection and p16INK4a immunostaining were performed. For HPV detection, whole tissue section-PCR analyses were performed by SPF10-DEIA-LiPA25 (version 1). As expected, HPV was detected more frequently in HPV-associated mixed carcinomas than in HPV-independent mixed carcinomas. Carcinomas with basaloid or warty features mixed with other SCC subtypes showed an HPV positivity rate of 46% (33 of 72 tumors) compared with 7% found in tumors with nonwarty/basaloid morphology (2 of 29 tumors). Eleven high-risk HPV genotypes were identified and the most common was HPV16 (65%) usually associated with basaloid morphology. p16INK4a immunostaining was positive in 76% of HPV-positive tumors. As in nonmixed carcinomas, although in lower proportion, a variable array of HPV genotypes was detected in mixed carcinomas. Apparently, the presence of a non-HPV component in an otherwise typical HPV-associated type tumor does adversely affect the prevalence of HPV positivity. Any amount of HPV-associated morphology superior to 20% in a mixed tumor is sufficient to classify them as HPV-associated, a WHO requirement. [ABSTRACT FROM AUTHOR]

Objective Human papillomavirus (HPV) vaccines can potentially control cervical cancer and help to reduce other HPV-related cancers. We aimed to estimate the relative contribution (RC) of the nine types (HPVs 16/18/31/33/45/52/58/6/11) included in the recently approved 9-valent HPV vaccine in female anogenital cancers and precancerous lesions (cervix, vulva, vagina and anus). Methods Estimations were based on an international study designed and coordinated at the Catalan Institute of Oncology (Barcelona-Spain), including information on 10,575 invasive cervical cancer (ICC), 1709 vulvar, 408 vaginal and 329 female anal cancer cases and 587 Vulvar Intraepitelial Neoplasia grade 2/3 (VIN2/3), 189 Vaginal Intraepitelial Neoplasia grade 2/3 (VaIN2/3) and 29 Anal Intraepitelial Neoplasia grade 2/3 (AIN2/3) lesions. Consecutive histologically confirmed paraffin-embedded cases were obtained from hospital pathology archives from 48 countries worldwide. HPV DNA-detection and typing was performed by SPF 10 -DEIA-LiPA 25 system and RC was expressed as the proportion of type-specific cases among HPV positive samples. Multiple infections were added to single infections using a proportional weighting attribution. Results HPV DNA prevalence was 84.9%, 28.6%, 74.3% and 90.0% for ICC, vulvar, vaginal and anal cancers, respectively, and 86.7%, 95.8% and 100% for VIN2/3, VaIN2/3 and AIN2/3, respectively. RC of the combined nine HPV types was 89.5% (95% confidence interval (CI): 88.8–90.1)-ICC, 87.1% (83.8–89.9)-vulvar, 85.5% (81.0–89.2)-vaginal, 95.9% (93.0–97.9)-female anal cancer, 94.1% (91.7–96.0)-VIN2/3, 78.7% (71.7–84.2)-VaIN2/3 and 86.2% (68.3–96.1)-AIN2/3. HPV16 was the most frequent type in all lesions. Variations in the RC of HPVs 31/33/45/52/58 by cancer site were observed, ranging from 7.8% (5.0–11.4)-female anal cancer to 20.5% (16.1–25.4)-vaginal cancer. Conclusions The addition of HPVs 31/33/45/52/58 to HPV types included in current vaccines (HPV16/18) could prevent almost 90% of HPV positive female anogenital lesions worldwide. Taking into account that most HPV-related cancers are ICC ones, the 9-valent HPV vaccine could potentially avoid almost 88% of all female anogenital cancers. [ABSTRACT FROM AUTHOR]