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Purpose: We sought to understand clinician-level barriers to providing HPV vaccination to survivors of childhood and young adult cancers (CYACs). Methods: We conducted 30-minute qualitative intervi...

Background Cervical cancer is the leading cause of cancer among women in Tanzania, with approximately 10,000 new cases and 7,000 deaths annually. In April 2018, the Government of Tanzania introduced 2 doses of human papillomavirus (HPV) vaccine nationally to adolescent girls to prevent cervical cancer, following a successful 2-year pilot introduction of the vaccine in the Kilimanjaro Region. Methods We interviewed key informants at the national level in Tanzania from February to November 2019, using a semi-structured tool to better understand national decision-making and program implementation. We conducted a comprehensive desk review of HPV vaccine introduction materials and reviewed administrative coverage data. Results Ten key informants were interviewed from the Ministry of Health, Community Development, Gender, Elderly, and Children, the World Health Organization, and other partners, and HPV vaccine planning documents and administrative coverage data were reviewed during the desk review. Tanzania introduced HPV vaccine to a single-age cohort of 14-year-old girls, with the decision-making process involving the Tanzania Immunization Technical Advisory Group and the national Interagency Coordination Committee. HPV vaccine was integrated into the routine immunization delivery strategy, available at health facilities and through outreach services at community sites, community mobile sites (>10 km from the health facility), and primary and secondary schools. Pre-introduction activities included trainings and microplanning workshops for health workers and school personnel at the national, regional, council, and health facility levels. Over 6,000 health workers and 22,000 school personnel were trained nationwide. Stakeholder and primary health care committee meetings were also conducted at the national level and in each of the regions as part of the advocacy and communication strategy. Administrative coverage of the first dose of HPV vaccine at the end of 2019 was 78%, and second dose coverage was 49%. No adverse events following HPV vaccination were reported to the national level. Discussion Tanzania successfully introduced HPV vaccine nationally targeting 14-year-old girls, using routine delivery strategies. Continued monitoring of vaccination coverage will be important to ensure full 2-dose vaccination of eligible girls. Tanzania can consider periodic intensified vaccination and targeted social mobilization efforts, as needed.

Background In April 2018, Tanzania introduced the human papillomavirus (HPV) vaccine nationally to 14-year-old girls, utilizing routine delivery strategies (i.e. vaccinating girls at health facilities and community outreach, including schools). We sought to assess awareness, feasibility, and acceptability of the HPV vaccination program among health workers and community-level stakeholders. Methods We conducted cross-sectional in-person surveys among health workers, school personnel, community leaders, and council leaders in 18 council areas across six regions of Tanzania in October–November 2019. Regions were purposively selected to provide demographic, geographic, and vaccination coverage variability; sub-regional levels used random or stratified random sampling. Surveys included questions on HPV vaccine training and knowledge, delivery strategy, target population, and vaccine and program acceptability. Descriptive analysis was completed for all variables stratified by respondent groups. Results Across the 18 councils, there were 461 respondents, including health workers (165), school personnel (135), community leaders (143), and council leaders (18). Over half of each respondent group (50–78%) attended a training or orientation on HPV vaccine. Almost 75% of the health workers and school personnel respondent groups, and less than half (45%) of community leaders correctly identified the target age group for HPV vaccine. Most (80%) of the health workers indicated HPV vaccination was available at health facilities and schools; most (79%) indicated that the majority of girls receive HPV vaccine in school. Approximately half (52%) of all respondents reported hearing misinformation about HPV vaccine, but 97% of all respondents indicated that HPV vaccine was either “very accepted” or “somewhat accepted” in their community. Conclusion The HPV vaccination program in Tanzania was well accepted by community stakeholders in 18 councils; adequate knowledge of HPV vaccine and the HPV vaccination program was demonstrated by health workers and school personnel. However, continued technical support for integration of HPV vaccination as a routine immunization activity and reinforcement of basic knowledge about HPV vaccine in specific community groups is needed. The Tanzania experience provides an example of how this vaccine can be integrated into routine immunization delivery strategies and can be a useful resource for countries planning to introduce HPV vaccine as well as informing global partners on how to best support to countries in operationalizing their HPV vaccine introduction plans.

Incidence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing globally and the human papillomavirus (HPV) has been linked to this increase. This study aimed to present a comprehensive overview of OPSCC trends in incidence rates by age group and investigate differences in risk factors profile. Netherlands Cancer Registry data from 1989-2018 were analyzed to calculate the annual percentage change (APC) over European standardized incidence rates by gender and age group using joinpoint regression software. Smoking, alcohol drinking and HPV-status were available for 2015-2018. During 1989-2018, 13 048 cases of OPSCC were reported with a male-to-female ratio of 2.1:1. The overall incidence rate increased by 5.4% (APC) annually from 1989 to 1996 but slowed thereafter by 1.2%. Significant declines were found in patients of 35-44 years (APCs -3.7%). Adults aged 45-59 years displayed significant increases from 1989 to 2001, followed by a significant decline. In patients >= 60 years, the incidence rates increased overall, with APC for women being consistently higher than men. The data on HPV status was available for 69% of the patients, of whom 47% were HPV+. Smoking and alcohol consumption were more prevalent, that is 75 and 76 % respectively. The declining trends of OPSCC for Dutch people aged 35-44 years from 1989 to 2018 and for those aged 45-59 years from 2002 onwards are inconsistent to trends reported elsewhere in the developed countries. The prevalence of smoking and drinking alcohol was quite high in all age groups, whereas the proportion of HPV-positivity was relatively low.

Background Cervical cancer is a leading cause of cancer-associated mortality among women in India, with 96,922 new cases and 60,078 deaths each year, almost one-fifth of the global burden. In 2018, Sikkim state in India introduced human papillomavirus (HPV) vaccine for 9–13-year-old girls, primarily through school-based vaccination, targeting approximately 25,000 girls. We documented the program’s decision-making and implementation processes. Methods We conducted a post-introduction evaluation in 2019, concurrent with the second dose campaign, by interviewing key stakeholders (state, district, and local level), reviewing planning documents, and observing cold chain sites in two purposefully-sampled community areas in each of the four districts of Sikkim. Using standard questionnaires, we interviewed health and education officials, school personnel, health workers, community leaders, and age-eligible girls on program decision-making, planning, training, vaccine delivery, logistics, and communication. Results We conducted 279 interviews and 29 observations in eight community areas across four districts of Sikkim. Based on reported administrative data, Sikkim achieved >95% HPV vaccination coverage among targeted girls for both doses via two campaigns; no severe adverse events were reported. HPV vaccination was well accepted by all stakeholders; minimal refusal was reported. Factors identified for successful vaccine introduction included strong political commitment, statewide mandatory school enrollment, collaboration between health and education departments at all levels, and robust social mobilization strategies. Conclusions Sikkim successfully introduced the HPV vaccine to multiple-age cohorts of girls via school-based vaccination, demonstrating a model that could be replicated in other regions in India or similar low- and middle-income country settings.

The introduction of the Human papillomavirus (HPV) vaccine has shown potential to not only prevent cervical cancer but also drive adolescents’ access to other health care services, even in low-income countries. Few studies have been conducted to date to identify best practices and estimate the acceptance, operational challenges and benefits of including broader adolescent health interventions into immunization efforts, knowledge which is essential to supporting widespread integration. In this paper we review the efforts undertaken by the government of Togo to integrate adolescent health programming with the HPV vaccination roll out. With the support of partners (GAVI, WHO, UNFPA and UNICEF), the country successfully completed, in 2017, two years of an HPV vaccine demonstration project, which entailed vaccinating 10-year-old girls against HPV in two selected districts of the country and integrating a health education component focused on puberty education / menstrual hygiene and hand washing practice. Our study is a post-implementation program evaluation, using mixed methods to assess key questions of feasibility and acceptability of an integrated adolescent package of care. It showed that the HPV vaccination in conjunction with the health education sessions was well received by the majority of health care providers, teachers and parents. Our study confirmed that in Togo it proved feasible to combine education and HPV vaccination in school-based service delivery. However, more operational research is neded to understand how to increase the impact and sustainability of the co-delivery of interventions. We did not analyze the health impact and cost implications of the intervention, which will be an important consideration for scaling up such integration efforts alongside routine immunization.

Background The introduction of primary HPV screening has doubled the number of colposcopy referrals because of the direct referral of HPV-positive women with a borderline or mild dyskaryosis (BMD) cytology (ASC-US/LSIL) triage test. Further risk-stratification is warranted to improve the efficiency of HPV-based screening. Methods This study evaluated the discriminative power of FAM19A4/miR124-2 methylation, HPV16/18 genotyping and HPV16/18/31/33/45 genotyping in HPV-positive women with BMD (n = 294) in two Dutch screening trials. Absolute CIN3+ risks and colposcopy referrals within one screening round were calculated. Results Methylation analysis discriminated well, yielding a CIN3+ risk of 33.1% after a positive result and a CIN3+ risk of 9.8% after a negative result. HPV16/18 and HPV16/18/31/33/45 genotyping resulted in a 27.6% and 24.6% CIN3+ risk after a positive result, and a 13.2% and 9.1% CIN3+ risk after a negative result. Colposcopy referral percentages were 41.2%, 43.2%, and 66.3% for FAM19A4/miR124-2 methylation, HPV16/18 and HPV16/18/31/33/45 genotyping, respectively. The CIN3+ risk after a negative result could be lowered to 2.8% by combining methylation and extended genotyping, at the expense of a higher referral percentage of 75.5%. Conclusion The use of FAM19A4/miR124-2 methylation and/or HPV genotyping in HPV-positive women with BMD can lead to a substantial reduction in the number of direct colposcopy referrals.

Background: Head and neck cancer (HNC) develops due to a number of risk factors, including infection of Human Papillomavirus (HPV). The genetic predisposition also plays an important role in deregulating different signaling pathways including the NF-KB pathway. Certain polymorphisms are reported to affect the NF-kB pathway genes. Objectives: The present research was conducted to study the association of HPV with NF-KB1 (p50) gene polymorphisms in HNC patients of the Pakistani population. Methods: Genomic DNA from HNC tumors samples was extracted using the Exgene SV DNA extraction Kit. Allele-specific PCR and direct sequencing were done for analysis of NF-κB1 SNPs 94ins/del (rs28362491), rs1598858 and rs4648068. Results: The genotypes AGrs1598858, AGrs4648068 and GGrs4648068 were associated with significantly increased risk of head and neck cancer in studied population. Furthermore the HNC cases with genotypes AGrs1598858 and GGrs4648068 displayed growing risk of HPV related cancers. Promotor region SNP 94ins/del (rs28362491) was not detected in studied population. Tobacco use, lymph nodes involvement and poorly differentiated tumors were positively associated with HPV induced cancers. Conclusion: It is the first comprehensive study from Pakistan, to evaluate the polymorphic variants of NF-κB1. Genotypes AGrs4648068, GGrs4648068, and AGrs1598858 of NF-κB1 gene are associated with increased risk of head and neck cancers in the studied HPV infected Pakistani population. It can be concluded that HPV infection, involvement of lymph nodes and tobacco use can act synergetic and add up in modulating HPV induced HNC with intronic SNPs of NF-κB1 gene in Pakistani population.

The study aimed to compare the performance of human papillomavirus (HPV)-based strategies to cytology for detecting cervical intraepithelial neoplasia grade 3 or worse (CIN3+) in routine program in China. The study included 50,434 women ages 30–64 years from January 2015 to December 2019, to assess four strategies: cytology with HPV triage (strategy 1), primary HPV testing with reflex cytology (strategy 2), primary HPV testing with HPV-16/18 genotyping and reflex cytology for non-16–18 high-risk HPV genotypes (strategy 3), and co-testing (strategy 4). The main outcomes were sensitivity for CIN3+ and colposcopy referral rate. Overall, the rates of HPV positivity and cytologic abnormality were 7.0% [95% confidential interval (CI), 6.8–7.2] and 3.5% (95% CI, 3.3–3.6], respectively. The sensitivity for CIN3+ were 88.5% for strategy 4, 83.2% for strategy 3, 64.6% for strategy 1, and 60.1% for strategy 2. The relative sensitivity of strategy 4 and strategy 3 compared with strategy 1 for detecting CIN3+ were 1.38 (95% CI, 1.24–1.54) and 1.29 (95% CI, 1.14–1.46), respectively. The colposcopy referral rates of strategies 4 and 3 were significantly higher than that of strategy 1 (2.4% and 2.2% vs. 1.4%, P < 0.001). In conclusion, co-testing and primary HPV testing with HPV-16/18 genotyping and reflex cytology improved the sensitivity for CIN3+ compared with cytology but increased the colposcopy referral rate. Long-term negative predicted value for HPV-negative women should be studied to determine the screening interval. Our study provides further evidence to the introduction of HPV-based strategies in China. Prevention Relevance: Both co-testing and primary HPV testing with HPV-16/18 genotyping and reflex cytology triage provided higher sensitivity for detecting CIN3+; however, the number of colposcopy referrals also increased compared with cytology in a routine program. It has great public health implications for the introduction of HPV-based screening strategies in China.

The prevalence of human papillomavirus (HPV) infection and HPV genotypes varies in different regions. However, there is little data on HPV prevalence and genotyping in Guangxi Province, South China. This study conducted a 10-year survey in a health center, to estimate the prevalence characteristics of HPV genotypes.By using polymerase chain reaction (PCR) amplification and nucleic acid molecular hybridization, the HPV genotypes were detected from 77,756 females who were patients of the Department of Obstetrics and Gynecology and those who visited the Health Management Center for a physical examination between August 2011 and November 2020. The prevalence, genotypes, age-related HPV infections, as well as chronological change of HPV prevalence, and the HPV genotype distribution were analyzed.The overall prevalence of HPV infection was 21.14% (16,439/77,756). The HPV infection rate differed significantly between the patients of the Department of Obstetrics and Gynecology and the women who underwent a physical examination (22.98% vs. 9.88%, p 0.05). The prevalence rates of high-risk HPV, low-risk HPV, mixed HPV (mixed high-risk, and low-risk HPV infection), and multiple HPV infections were 18.96% (14,739/77,756), 4.09% (3178/77,756), 1.90% (1478/77,756), and 4.94% (3838/77,756), respectively. The most prevalent genotypes were HPV 52, 16, and 58. The age-associated HPV prevalence showed bimodal curves, with the first peak at25 years and the second peak at56 years.This study provides baseline data on the HPV prevalence in the general female population of Nanning, Guangxi Province. Women25 and56 years old faced the greatest threat of HPV infection, and HPV 52, 16, and 58 were the most common genotypes.

Human papillomavirus (HPV) infection in men is a serious issue because it is associated with genital warts, anogenital cancers, and HPV transmission to their sex partners. This study aimed to investigate the prevalence and genotypes of HPVs in Vietnamese male patients hospitalized with sexually transmitted infection (STI) symptoms between 2016 and 2020 by using PCR and reverse dot blot hybridization analysis. HPV DNA was detected in 191/941 (20.3%) penile cell samples. The HPV patient's mean age was 30.3 in the range of 16- and 69-year-old. The highest HPV prevalence (84.7%) was found in patients between 20- and 39-year-old. A total of 313 HPV genotypes were identified. Multiple-infection rate was 42.9%. The most common high-risk (HR)-HPV genotypes were HPV-16 (8.0%), HPV-51 (7.7%), HPV-52 (4.8%), HPV-56 (4.2%), and HPV-18 (3.8%). Furthermore, HPV-11 and HPV-6 genotypes were the two most common low-risk (LR)-HPV genotypes with the rate of 36.7% and 21.4%, respectively. Notably, HPV-52 was found circulating in Vietnam for the first time. In conclusion, this study results showed that HPV prevalence in Vietnamese male patients was common and diverse. In addition, regarding public health and cancer prevention, the inclusion of the HPV vaccination into the national vaccination program for both men and women is recommended. This article is protected by copyright. All rights reserved.

Introduction To direct interventions, the Florida counties with the greatest risk of current and future human papillomavirus‒associated cancers were identified by estimating county-level (1) percentages of adolescents aged 13–17 years who initiated (≥1 dose) and were up to date (2–3 doses) for the human papillomavirus vaccine and (2) human papillomavirus‒associated cancer incidence rates. Methods Records were obtained for human papillomavirus vaccinations from the Florida immunization registry (2006–2019), incident cancer cases from the Florida registry (2013–2017), and annual population counts from the Florida Department of Health (2006–2019). In 2020, annual county-level human papillomavirus vaccine initiation, human papillomavirus vaccine up-to-date, and age-adjusted human papillomavirus‒associated cancer incidence rates were estimated. Results Among adolescents aged 13–17 years, average 2018–2019 county-specific human papillomavirus vaccine initiation ranged from 38% to 100% for females and from 34% to 96% for males. Up-to-date estimates ranged from 20% to 72% for females and from 24% to 77% for males. The majority (78%) of counties with initiation and up-to-date estimates within the lowest tercile were located in Northern Florida. County-specific 2013–2017 annualized, adjusted human papillomavirus‒associated cancer incidence rates ranged from 0 to 29.8 per 100,000 among females and from 5.4 to 24.1 per 100,000 among males. Counties within the highest tercile for human papillomavirus‒associated cancers were primarily (90% for females and 77% for males) located in Northern Florida. Conclusions Human papillomavirus‒associated cancer risk varies widely across Florida counties, with particularly high risk within Northern Florida. Targeting interventions toward counties with low vaccination and high cancer rates may reduce human papillomavirus‒associated cancers.

While platinum-based chemotherapy, radiation therapy and or surgery are effective in reducing human papillomavirus (HPV) driven cancer tumours, they have some significant drawbacks, including low specificity for tumour, toxicity, and severe adverse effects. Though current therapies for HPV-driven cancers are effective, severe late toxicity associated with current treatments contributes to the deterioration of patient quality of life. This warrants the need for novel therapies for HPV derived cancers. In this short review, we examined RNA-based therapies targeting the major HPV oncogenes, including short-interfering RNAs (siRNAs) and clustered regularly interspaced short palindromic repeats (CRISPR) as putative treatment modalities. We also explore other potential RNA-based targeting approaches such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and mRNA vaccines as future treatment modalities for HPV cancers. Some of these technologies have already been approved for clinical use for a range of other human diseases but not for HPV cancers. Here we explore the emerging evidence supporting the effectiveness of some of these gene-based therapies for HPV malignancies. In short, the evidence sheds promising light on the feasibility of translating these technologies into a clinically relevant treatment modality for HPV derived cancers and potentially other virally driven human cancers.

Aims To evaluate whether biomarkers derived from fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) performed prior to (prePET) and during the third week (interim PET; iPET) of radiotherapy can predict treatment outcomes in human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPC). Materials and methods This retrospective analysis included 46 patients with newly diagnosed OPC treated with definitive (chemo)radiation and all patients had confirmed positive HPV status (HPV+OPC) based on p16 immunohistochemistry. The maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV) and total lesional glycolysis (TLG) of primary, index node (node with the highest TLG) and total lymph nodes and their median percentage (≥50%) reductions in iPET were analysed, and correlated with 5-year Kaplan–Meier and multivariable analyses (smoking, T4, N2b-3 and AJCC stage IV), including local failure-free survival, regional failure-free survival, locoregional failure-free survival (LRFFS), distant metastatic failure-free survival (DMFFS), disease-free survival (DFS) and overall survival. Results There was no association of outcomes with prePET parameters observed on multivariate analysis. A complete metabolic response of primary tumour was seen in 13 patients; the negative predictive value for local failure was 100%. More than a 50% reduction in total nodal MTV provided the best predictor of outcomes, including LRFFS (88% versus 47.1%, P = 0.006, hazard ratio = 0.153) and DFS (78.2% versus 41.2%, P = 0.01, hazard ratio = 0.234). More than a 50% reduction in index node TLG was inversely related to DMFFS: a better nodal response was associated with a higher incidence of distant metastatic failure (66.7% versus 100%, P = 0.009, hazard ratio = 3.0). Conclusion The reduction (≥50%) of volumetric nodal metabolic burden can potentially identify a subgroup of HPV+OPC patients at low risk of locoregional failure but inversely at higher risk of distant metastatic failure and may have a role in individualised adaptive radiotherapy and systemic therapy.

Background Infections with human papillomaviruses (HPVs) may enter a latent state, and eventually become reactivated following loss of immune control. It is unclear what proportion of incident HPV detections are reactivations of previous latent infections vs new transmissions. Methods The HPV Infection and Transmission among Couples through Heterosexual activity (HITCH) cohort study prospectively followed young newly formed heterosexual partners recruited between 2005 and 2011 in Montréal, Canada. We calculated the fraction of incident HPV detections nonattributable to sexual transmission risk factors with a Bayesian Markov model. Results are the median (2.5th-97.5th percentiles) of the estimated posterior distribution. Results A total of 544 type-specific incident HPV detection events occurred in 849 participants; 33% of incident HPV detections occurred in participants whose HITCH partners were negative for that HPV type and who reported no other sex partners over follow-up. We estimate that 43% (38%–48%) of all incident HPV detections in this population were not attributable to recent sexual transmission and might be potentially reactivation of latent infections. Conclusions A positive HPV test result in many cases may be a reactivated past infection, rather than a new infection from recent sexual behaviors or partner infidelity. The potential for reactivation of latent infections in previously HPV-negative women should be considered in the context of cervical cancer screening.

The International Endocervical adenocarcinoma Criteria and Classification (IECC) categorizes tumors into human papilloma virus (HPV) associated (HPVA), not associated (NHPV), and invasive adenocarcinoma not otherwise specified (IA NOS). HPVA and NHPV encompass 11 histotypes and an algorithm of mucin content, HPV ribonucleic acid (RNA), estrogen receptor and GATA3 is proposed for the diagnosis of most. In this study, the IECC algorithm's diagnoses were compared with hematoxylin and eosin (H&E) based IECC histotyping. Kappa statistics measured performance agreement. With additional markers, hierarchical clustering by random forest (RF) classification identified the most discriminating between tumor types, and investigated other algorithms. Three pathologists independently reviewed digitized H&E images of n=152 primary cervical adenocarcinomas for IECC histotype and mucin content, and tissue microarrays for expression of HPV RNA by in situ hybridization and 16 antibodies by immunohistochemistry. Results were finalized by consensus. There were n=113 HPVA, n=22 NHPV, and n=17 IA NOS. Mucin was obvious in n=36 and limited in n=116. Among n=124 with satisfactory test results, HPV RNA was positive in n=96, estrogen receptor in n=72, and GATA3 in n=15. The IECC algorithm diagnosed n=99 which agreed with H&E histotyping in n=64 for a fair κ of 0.36 (95% confidence interval, 0.21-0.50): n=12 were undiagnosed and n=13 were IA NOS. Small sample sizes restricted RF to HPVA versus NHPV which were discriminated by p16, HPV RNA, and MUC6 with an area under the curve of 0.74 (95% confidence interval, 0.58-0.90). The IECC algorithm for histotyping under-performed. The RF algorithmin for categorization was favorable, but validation in larger studies and investigation of additional algorithms to discriminate between all IECC histotypes are needed.

BACKGROUND Human papillomavirus-related oropharyngeal squamous cell carcinoma (HPV-OPSCC) presents frequently as metastasis in a neck lymph node that may be cystic or necrotic. Fine-needle aspiration (FNA) biopsies are often first-line diagnostic procedures. p16 immunohistochemistry (IHC) is a surrogate marker for high-risk HPV (hrHPV) infection but can be challenging to interpret. This study evaluated the use of hrHPV in situ hybridization (ISH) in cytology cell blocks of cystic neck lesions. METHODS Twenty-four FNA cases with cell blocks and surgical correlates were evaluated. p16 IHC and hrHPV ISH were assessed on cell blocks (C-p16 and C-hrHPV ISH), and hrHPV ISH on surgical samples (S-hrHPV ISH). All results were classified as negative, positive, or equivocal. RESULTS Two cases were excluded because of insufficient tissue on recut. On the basis of C-hrHPV ISH cases, 12 were positive, 5 were negative, and 5 were equivocal. All 12 positive C-hrHPV ISH cases had concordant S-hrHPV ISH with no false positives. Of the 5 negative C-hrHPV ISH cases, 4 had concordant S-hrHPV ISH, and 1 had a discordant S-hrHPV ISH. Of the 5 equivocal C-hrHPV ISH cases, S-hrHPV ISH were both positive and negative. Fourteen cases were equivocal by C-p16; 9 cases were reliably classified by C-hrHPV ISH (5 positive, 4 negative; 64%). CONCLUSIONS C-hrHPV ISH can be reliably used, especially when positive. A negative or equivocal interpretation of C-hrHPV ISH may warrant repeat testing. Compared to C-p16, C-hrHPV ISH is more frequently diagnostic and could be helpful for HPV-OSCC diagnosis and management.

AIMS To compare the clinical performance of high-risk human papillomavirus (hrHPV) DNA detection between urine and cervical samples collected from the same patient for the detection of CIN2+ lesions (high-grade squamous intraepithelial lesions or cervical cancer lesions). The secondary objectives were to evaluate agreement among hrHPV genotypes and to compare patient satisfaction between urine and cervical sample collection. METHODS This prospective cross-sectional study enrolled 96 women with abnormal cervical cytology who attended the colposcopy clinic at Siriraj Hospital (Bangkok, Thailand) between July 2016 and January 2017. Self-collected random-voiding and first stream urine samples were collected into a universal sterile urine container and immediately mixing with preservative before the pelvic examination. Cervical tissue sampling was performed according to standard treatment guidelines. Both specimens were sent for extraction and detection of hrHPV by Anyplex II HPV high-risk testing. Study patients were surveyed to compare patient satisfaction between urine and cervical sample collection. RESULTS Carcinogenic hrHPV positive rate was 73% in urine samples and 81% in cervical samples. The sensitivity for HPV in the detection CIN2+ was high in both the urine and cervical groups at 86.2% and 94.8%, respectively. Agreement between the urine and cervical groups for HPV 16 or 18 detection was high, with kappa values of 0.86 for subtypes 16/18. Urine specimen collection had significantly higher satisfaction and acceptability than cervical specimen collection. CONCLUSION Urine hrHPV testing by real-time polymerase chain reaction demonstrated high sensitivity and accuracy for the detection of CIN2+ lesions, with very good agreement when compared with cervical sample testing.

Purpose This study aimed at targeting shared factors that influence the prevention of multiple diseases, which can help address various health problems simultaneously. We identified correlates of human papillomavirus (HPV) vaccination that overlap with COVID-19 vaccination. Design Cross-sectional survey data. Setting Online Qualtrics recruitment panel. Subject Religious parents of 342 adolescents who were unvaccinated for HPV (response rate was 68.1%). Measures Outcome variables were COVID-19 vaccination intention for (1) self, (2) child, and (3) HPV vaccination intention for child. Independent variables were psychological factors. Covariates were sociodemographic and socioeconomic factors. Analysis We conducted multivariate linear regressions on each outcome variable after controlling for covariates. Result Some psychological correlates of HPV overlapped as protective factors for all three outcomes. Higher perceived vulnerability of child to HPV was associated with higher vaccination intention against COVID-19 for self (β = .37, 95% confidence interval [CI] = .25–.48), child (β = .32, .21–.44), and HPV for child (β = .38, .27–.49). Higher perceived response efficacy of HPV vaccine was associated with greater vaccination intention against COVID-19 for self (β = .46, .33–.59), child (β = .41, .28–.53), and HPV for child (β = .75, .64–.85). Conclusion Given the overlap in HPV and COVID-19 vaccination correlates, interventions should target shared factors that address both diseases to maximize public health efforts. A major limitation of this study is the inability to measure the actual vaccination behavior.

Cervical cancer is the fourth most frequent cancer in women worldwide, representing nearly 8% of all female cancer deaths every year. The majority of cases of cervical cancer are caused by human papillomavirus (HPV); however, up to 5% of tumors are not associated with HPV-persistent infection and, moreover, the new WHO Female Genital Tumors classification subdivided cervical squamous and adenocarcinomas into HPV-associated and HPV-independent tumors. Based on this new information, the aim of this review is to provide an overview of HPV-independent cervical cancer, evaluating diagnostic techniques, molecular profiles, and clinical outcomes. The HPV-independent tumors are characterized by a differentiated molecular profile with lower proliferative activity, a p53 immunostaining, a decreased expression of cyclin-dependent kinase inhibitor proteins, such as p16, p14, and p27, and alterations in PTEN, p53, KRAS, CTNNB1, ARID1A, and ARID5B. HPV-independent tumors are associated with both adenocarcinomas and squamous histologic subtypes, with lymph node involvement in the early stages, more distant metastasis, and generally worse oncological outcomes. Thus far, no specific therapeutic strategies have been developed based on HPV status; however, with advancing knowledge of differences in the molecular profiles and possible targetable alterations, novel approaches may offer potential options in the near future. Investigators should report on clinical outcomes, evaluating the overall response rates to specific treatments, and consider new biomarkers to establish more accurate prognostics factors.

OBJECTIVE To evaluate risk factors associated with the persistence of human papillomavirus (HPV) after cervical excision in patients with high-grade squamous intra-epithelial neoplasia (HSIL). METHODS A retrospective cohort study enrolled 550 patients who underwent cervical excision for HSIL between January 2015 and January 2018. The effects of various factors were assessed using univariate and multi-variate analyses. RESULTS The mean age of patients was 42.6 [standard deviation (SD) 8.7, range 22-64] years, and the mean duration of follow-up was 29.0 (SD 4.8, range 24-36) months. Persistent HPV infection after cone excision was detected in 78 (14.2%) patients. Univariate logistic regression analysis revealed that advanced age (>35 years), menopausal status, HPV type (HPV16/18), abnormal vaginal micro-ecological morphology, type of excision (loop electrosurgical excision procedure) and positive margin were closely associated with the persistence of HPV. Multi-variate analysis indicated that menopausal status [odds ratio (OR) 4.708, 95% confidence interval (CI) 2.770-8.001; p

Highlights • HPV infection in men having sex with men (MSM) was studied in two cities of Vietnam • Prevalence of any HPV and HPV16/18 among MSM was 32.3% and 11.0%, respectively • High-risk HPV infections in MSM were associated with risky sexual behaviours • A targeted HPV vaccination strategy would be beneficial for MSM in Vietnam, Objectives Men who have sex with men (MSM) are at risk of human papillomavirus (HPV)-related cancers, while published data are scarce. This study determined HPV prevalence and risk factors in MSM in Vietnam to inform HPV prevention strategies in this key population. Methods A cross-sectional study of 799 MSM aged 16-50 years was conducted in Vietnam in 2017-2018. Information was collected on risk behaviours, and knowledge of HPV and anal cancer; rectal swabs were taken to detect anal HPV infection. An in-house polymerase chain reaction and Genoflow HPV array test kit were used for HPV detection and genotyping. Results The median age of the study participants was 25 years (range 18-52). Overall prevalence of any HPV and HPV16/18 infection was 32.3% and 11.0%, respectively. A higher prevalence of high-risk HPV infection to all 14 types tested was found in Ho Chi Minh City (30.9%) than in Hanoi (18.4%). High-risk HPV infection was associated with inconsistent condom use and history of engaging in sex under the influence of drugs (adjusted odds ratio (aOR), 2.27; 95% CI, 1.48-10.67), as well as having multiple sexual partners (aOR, 1.01; 95% CI, 1.00–1.02). Conclusions High-risk anal HPV infections in Vietnamese MSM were significantly associated with risky sexual behaviours. A targeted HPV vaccination strategy would have substantial benefit for MSM in Vietnam.

Background Anal squamous intraepithelial lesions (ASIL), strongly related to human papilloma virus (HPV) infection, is more prevalent among men who have sex with men (MSM). However, no such data are available for Pakistan yet, and neither HPV vaccination nor anal-cytology screening is implemented in Pakistan. The purpose of this first ever study was to assess the prevalence of HPV-related anal cytological abnormalities among MSM and transgender women living with and without HIV infection in Pakistan. Methods We conducted a cross-sectional study from March 2016 to November 2017 at sexual health centers run by the Perwaaz Trust and the National AIDS Control Program in Karachi. The study enrolled MSM and transgender women aged greater-than-and-equal-to-18-years who reported anal sex in the preceding 6 months. We collected two anal samples for liquid-based cytology and HPV type testing by PCR, and socio-demographic and behavioral data were collected through face-to face interviews. ASIL and its associations with biological and behavioral risk factors were analyzed through Cox regression for prevalence ratios (PR) and corresponding 95% confidence intervals (CIs). Results Out of 271 qualifying participants, 79% were MSM and 21% transgender women. The mean age was 28.8 (± 8) years. Almost 35% (93/271) of the study population had ASIL detected, ASIL was significantly more common among participants living with HIV than in HIV negative ((50/118) 42.4%; vs. (43/153) 28.1%) (p ≤ 0.001). Among ASIL, 66% (61/93) had low-grade squamous intraepithelial lesions (LSIL), and 3.6% (3/93) had high-grade squamous intraepithelial lesions (HSIL). The overall, HPV16 positivity was 35.5% (33/93) among all abnormal anal lesions and all 3 HSIL were HPV16 positive, however, HPV16 positivity could show its association with ASIL detection in univariate model only (PRcrude: 2.11(1.39–3.18)). Moreover, any HR-HPV type (PR 3.04; 95% CI 1.75–5.26), concurrent sexually transmitted infection (STI) (2.13; (1.28–3.55)) and HIV + /HPV + coinfection (1.75; (1.07–2.88)) remained independently associated with ASIL in the multivariate model. Conclusions Abnormal anal cytology among MSM and transgender is prevalent enough to consider optimal screening regimens. Further studies are required to see if periodic anal cytology can be made part of HIV care and treatment programs among MSM in Pakistan.

Cidofovir is a broad-spectrum antiviral agent that has shown efficacy against skin lesions caused by human papillomavirus (HPV). We present a case of extensive verruca vulgaris lesions refractory to imiquimod that was responsive to topical cidofovir therapy, and analyze other case series in the literature of successful treatment of benign HPV-associated skin lesions with topical cidofovir. Topical cidofovir’s favorable response rate and tolerability make it a useful treatment option for patients of differing ages and immune status who have nonmalignant HPV-associated skin lesions and desire topical therapy.

AIM The aim of this study was to evaluate the clinical performance for detecting cervical intraepithelial neoplasia (CIN) 2 or higher lesions among available human papillomavirus infection (HPV) genotyping tests in Korea. METHODS Eligible patients visited 13 tertiary hospitals for colposcopic biopsy following cervical cytology and HPV genotyping test between January and December 2018. Baseline characteristics including age, body mass index (BMI), and parity were collected from 3798 patients. The performance of the Roche Cobas HPV 4800 was evaluated against other domestic HPV assays to detect CIN2 or higher. RESULTS A total of seven types of HPV genotyping tests were analyzed in the research institutes. A total of 1358 patients (35.8%) tested Anyplex II HPV 28 and 701 patients (18.5%) tested Cobas 4800 HPV. The overall sensitivity in the detection of CIN2 or higher was 41.5% (38.9-44.1) in patients positive for HPV 16/18. The Cobas test for HPV 16/18 was concordant with other assays evaluated for detection of CIN2 or higher and showed sensitivity of 46.6%, which was not significantly different from other assays. Although Anyplex II HPV28 (Seegene) showed slightly decreased sensitivity for detecting CIN2 or higher lesion with HPV 16/18 positive (39.8%, p

Background Interplay between vaginal microbiome and human papillomavirus (HPV) remains unclear, partly due to heterogeneity of microbiota. Methods We used data from 546 women enrolled in a cross-sectional study in 5 Brazil. We genotyped vaginal samples for HPV and sequenced V3–V4 region of 16S rRNA gene for vaginal microbiome analysis. We used stepwise logistic regression to construct 2 linear scores to predict high-risk HPV (hrHPV) positivity: one based exclusively on presence of individual bacterial taxa (microbiome-based [MB] score) and the other exclusively on participants’ sociodemographic, behavioral, and clinical (SBC) characteristics. MB score combined coefficients of 30 (of 116) species. SBC score retained 6 of 25 candidate variables. We constructed receiver operating characteristic curves for scores as hrHPV correlates and compared areas under the curve (AUC) and 95% confidence intervals (CI). Results Overall, prevalence of hrHPV was 15.8%, and 26.2% had a Lactobacillus-depleted microbiome. AUCs were 0.8022 (95% CI, .7517–.8527) for MB score and 0.7027 (95% CI, .6419–.7636) for SBC score (P = .0163). Conclusions The proposed MB score is strongly correlated with hrHPV positivity—exceeding the predictive value of behavioral variables—suggesting its potential as an indicator of infection and possible value for clinical risk stratification.

Objective Organised cervical cancer screening was started in Estonia in 2006, but participation is still low. Human papillomavirus (HPV) self-sampling has proved to increase screening uptake. This study addressed the feasibility of HPV self-sampling and the acceptance of this method among long-term screening non-attenders. Methods A randomised intervention study was conducted in Estonia in 2020. Women born in 1958–1983 without a Pap smear in 2013–2019 were identified in the Estonian Health Insurance Fund database. From them, 12,000 women were randomly allocated to three equal-sized study groups. The opt-out group received a questionnaire and a Qvintip® sampling device by regular mail. Two opt-in groups received a questionnaire and an e-mail invitation to order a self-sampler online; one received Qvintip and the other Evalyn® Brush. Participantś background characteristics were obtained from the Population Register. The effect of covariates on participation rate was estimated with multivariate Poisson regression. Acceptance of self-sampling was analysed according to agreement with statements in the questionnaire. Results The overall participation rate was 16% with significant differences between opt-out (26%) and opt-in (11%) groups. Compared to the opt-out Qvintip group, adjusted relative risks for the Qvintip and Evalyn Brush opt-in groups were 0.41 (95% confidence interval (CI) 0.37–0.45) and 0.44 (95% CI 0.40–0.49), respectively. Participation was associated with living place, citizenship, and education. Self-sampling was well accepted: 98% agreed that it was easy to use, 88% preferred it as a screening method in future. Conclusions The results show the feasibility and good acceptance of HPV self-sampling among long-term screening non-attenders in Estonia.

Objectives The present study aimed to evaluate human papillomavirus (HPV) occurrence in sinonasal inverted papilloma (SNIP), and to assess factors associated with HPV positivity and SNIP recurrence. Study design Prospective study. Methods We prospectively collected clinical data and fresh tissue specimens from 90 consecutive patients treated for SNIP at Helsinki University Hospital, between 2015 and 2019. Fourteen patients with recurrent SNIP underwent repeated tumor sampling. All tissue specimens were analyzed for the presence of HPV. Factors associated with SNIP recurrence and HPV positivity were assessed. Results Among 107 SNIP specimens, 14 (13.1%) were positive for low-risk HPV and 6 (5.6%) were positive for high-risk HPV. HPV positivity was associated with an increased risk of recurrence (P = .004). Smoking was significantly associated with HPV positivity in SNIP (P = .01), but a history of HPV-related diseases or patient sexual habits did not correlate with HPV positivity. The recurrence rate was lower among patients with SNIP that underwent an attachment-oriented resection, compared to patients treated without attachment-oriented resections (78.6% vs 25.8%, P Conclusions The risk of SNIP recurrence was highly associated with 1) HPV positivity and 2) surgery without an attachment-oriented resection. Oncogenic HPV was rare in SNIP. Level of evidence 3 Laryngoscope, 2021.

Objective The objective of the review is to investigate overall survival in patients with human papillomavirus positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC) comparing standard- versus reduced-dose radiotherapy.Introduction: The improved survival of patients with HPV+ compared to HPV- (HPV negative) OPSCC has raised the question regarding reducing the total radiation treatment dose delivered to patients with HPV+ OPSCC. A de-escalated radiotherapy protocol may provide equal oncological benefit with reduced adverse events/toxicity. Inclusion criteria We will include any adult patients aged 18 years or older who have undergone curative intent treatment for HPV+ OPSCC. These patients can be of any stage at the time treatment is initiated. Exclusion criteria will include pre-clinical or animal-based studies, patients with non-squamous cell carcinoma lesions of the oropharynx, primary lesions in other head and neck sites, or if treatment is palliative in nature. Methods A three-step search strategy will be conducted to identify relevant articles for inclusion through MEDLINE (PubMed and Ovid), CINAHL (EBSCO), Embase (Elsevier), Web of Science, Scopus, and gray literature sources. These articles will be assessed against our inclusion and exclusion criteria at a title and abstract level, as well as at full-text level. Remaining studies will be critically appraised based on their trial design. Data extraction will occur for all studies and, where possible, will be pooled with statistical meta-analysis. Systematic review registration number PROSPERO CRD42021252161.

PURPOSE Squamous cell carcinoma metastasis of the head and neck with unknown primary tumor (CUP) comprises a diagnostic challenge. Human papillomavirus (HPV) testing on cytologic specimens is gaining increasing focus as this may facilitate an early diagnosis of HPV-induced oropharyngeal carcinoma. This study aimed to prospectively assess PCR-based HPV-DNA testing on FNA smears in a clinical setting. METHODS Patients referred to a tertiary Head and Neck Cancer Center with suspected CUP were included from November 2016 to November 2018. Scraped cell material from FNA smears was analyzed for HPV-DNA with PCR using general primers (GP5 + /GP6 +) and correlated with the origin and histology of the primary tumor (oropharynx vs. outside oropharynx or benign tumor). The turn-around time reflecting the workflow for HPV-DNA testing by PCR was also calculated. RESULTS A total of 93 patients were enrolled in the study. The sensitivity and specificity were 86.7% [95% CI 75.4-94.1%] and 92.0% [95% CI 74.0-99.0%], and the positive and negative predictive values were 96.3% [95% CI 87.3-99.0%] and 74.2% [95% CI 59.9-84.7%], respectively. The turn-around time for HPV testing was a mean four calendar days. CONCLUSION HPV-DNA testing on FNA smears can be performed within a reasonable timeframe and can guide for the detection of an HPV-positive oropharyngeal primary tumor in the clinical setting for patients presenting with CUP of the head and neck.

In this study the authors' investigated the effect of group education on human papillomavirus (HPV) on level of knowledge and health beliefs for HPV infection and vaccine. The study was semi-experimental with a pre- and post-test education model. In total, 110 mothers of secondary school students, 55 in education group, and 55 in control group participated. The groups were educated on different content and three evaluations (pre-education, post-education, and six months following the education) were made. HPV knowledge and belief scores of the education group increased compared to pre-education and control group scores (

Predictions of cervical cancer burden and the impact of measures taken to control this cancer are usually data-demanding and based on complex assumptions. We propose a predictive method (called PANDORA) based on human papillomavirus (HPV) prevalence, measured 1993–2008, and cervical cancer incidence (CCI), measured 1993–2012, in the same birth cohorts from different worldwide locations, informed by data on age at detection of high-risk HPV and sexual debut. The model can predict CCI among high-risk HPV–positive women and predict CCI up to 14 years following high-risk HPV detection. We found CCI to increase during the 14 years following high-risk HPV detection in unscreened women aged

Purpose To assess and improve school nurse knowledge of HPV-associated cancers. Design An experimental quality improvement study. Methods At a continuing education regional conference, an interactive HPV education session was provided. Pre- and post-education surveys were completed by attendees. Findings After the educational intervention, 89.9% of nurses indicated a change in knowledge and 83.2% indicated a planned change in practice. Conclusions An education intervention aimed at school nurses can be impactful in broadening the understanding of HPV oncogenesis. Clinical evidence Educational interventions can be a strategy to increase school nurse knowledge and subsequently patient knowledge about HPV associated cancers.

Owing to the presence of known tumor-specific viral antigens, human papillomavirus (HPV)-associated cancers are well suited for treatment with immunotherapy designed to unleash, amplify or replace the T cell arm of the adaptive immune system. Immune checkpoint blockade designed to unleash existing T cell immunity is currently Food and Drug Administration approved for certain HPV-associated cancers. More specific immunotherapies such as therapeutic vaccines and T cell receptor-engineered cellular therapy are currently in clinical development. Such therapies may offer more specific immune activation against viral tumor antigens and decrease the risk of immune-related adverse events. Current and planned clinical study of these treatments will determine their utility in the treatment of patients with newly diagnosed advanced stage or relapsed HPV-associated cancer.

Purpose Human papillomavirus (HPV) vaccination in the United States has been recommended for girls since 2006 and for boys since 2011. However, settings of receiving HPV vaccination have not been assessed. The purpose of this study is to assess settings of receiving HPV vaccination among adolescents in order to understand what strategies are needed to improve vaccination uptake. Methods Data from the 2018 National Immunization Survey–Teen (NIS–Teen) were analyzed to assess place of HPV vaccination overall, and by gender, quarter, and other selected variables among adolescents in the United States. The 2016–2018 NIS–Teen data were combined to assess state-specific place of HPV vaccination. Results Among vaccinated adolescents aged 13–17 years, a doctor's office was the most common place where HPV vaccination was received (79.2%), followed by clinics, health centers, or other medical facilities (13.5%), health department (4.1%), hospital or emergency room (2.3%), schools (.5%), and pharmacies or stores (.4%). Overall, 99.1% of adolescents aged 13–17 years received HPV vaccination at medical settings and only .9% at nonmedical settings. Reported vaccination in nonmedical settings by state ranged from less than .1% in Delaware, Florida, and New Hampshire to 4.1% in North Dakota, with a median of 1.0%. Conclusions Doctor's offices were the most common medical setting for adolescents to receive HPV vaccination. Less than 1% of adolescents received vaccination at nonmedical settings. Continuing work with medical and nonmedical settings to identify and implement appropriate strategies are needed to improve HPV vaccination coverage among adolescents.

Background The objective of this study, the first of its kind in Kosovo, is to determine the level of Kosovo women’s knowledge and awareness of HPV infection, HPV vaccination, and its relation to cervical cancer. Methods This cross-sectional study was conducted from July to October 2018 at the Clinic of Obstetrics and Gynecology at the Hospital and University Clinical Service of Kosovo. Results Out of 800 questionnaires distributed, 645 were completed and returned (80.6%). Only 0.5% of women were vaccinated against HPV. The majority of respondents (66.4%) had no previous knowledge of HPV (human papillomavirus). Only 27.6% of respondents were aware that HPV is responsible for cervical cancer. About two-thirds (70.1%) of respondents had never heard of the HPV vaccine, and only 24% knew that the HPV vaccine can prevent cervical cancer. Conclusion The level of vaccination against HPV and the level of knowledge and awareness of HPV infection is extremely low. Higher education, younger age, and living in an urban area were favorable factors and correlated with awareness of HPV infection, vaccination against it, and its relation to cervical cancer. Based on this study, there is an immediate need for developing an educational program on HPV infection and the importance of HPV vaccination as a preventative measure against developing cervical cancer.

Squamous cell carcinoma of the oropharynx (OPC) consists of human papillomavirus (HPV)-negative disease caused by tobacco and alcohol use, and HPV-positive disease caused by the sexually transmitted infection HPV. These entities have unique but overlapping risk factors, epidemiologic trends, staging systems, and survival outcomes. HPV-positive tumor status confers a significant survival benefit compared with HPV-negative disease. OPC treatment entails a combination of surgery, radiation, and chemotherapy. Ongoing trials will determine whether treatment of HPV-related disease may be safely deintensified to decrease morbidity. Emerging HPV-related biomarkers are under study as tools to inform screening, diagnosis, treatment, and surveillance for HPV-positive OPC.

OBJECTIVES/HYPOTHESIS We aim to 1) evaluate trends in adjuvant treatment of human papilloma virus (HPV)-related oropharyngeal cancer; 2) assess change in complications and functional outcomes over time; and 3) assess change in overall and disease-free survival (DFS) over time. STUDY DESIGN Retrospective analysis. METHODS Charts of patients who underwent transoral robotic surgery for HPV-related oropharyngeal cancer between 2011 and 2019 were reviewed. Trend analysis was used to compare rate of adjuvant treatment over time. The Kaplan-Meier method was conducted to analyze overall survival (OS) and DFS. RESULTS Three hundred and forty-two patients met inclusion criteria. One hundred and sixty-three (47.7%) patients underwent adjuvant radiation, and 90 (26.3%) patients underwent adjuvant chemoradiation. Rate of extranodular extension decreased significantly from 38.9% to 24.0% (P = .004). Rate of adjuvant therapy decreased significantly from 90.9% to 62.5% between 2011 and 2019 (P = .001). In patients who received adjuvant treatment, rate of adjuvant chemoradiation therapy decreased significantly from 40.0% to 20.0% (P

Introduction: Human papillomavirus (HPV), p16, and p53 have been investigated as prognostic markers in various HPV-related cancers. Within the field of vaginal cancer, however, the evidence remains sparse. In this systematic review, we have compiled the presently published studies on the prognostic significance of HPV and immunohistochemical expression of p16 and p53 among women with vaginal cancer. Material and methods: We conducted a systematic search of PubMed, Embase, and Cochrane Library to identify relevant studies published until April 2021. We included studies reporting survival after histologically verified vaginal cancers tested for HPV, p16, and/or p53. Survival outcomes included overall survival, disease-free survival, disease-specific survival, and progression-free survival. Results: We included a total of 12 studies. The vast majority of vaginal cancer cases included in each study were squamous cell carcinomas (84%–100%). Seven studies reported survival after vaginal cancer according to HPV status, and the majority of these studies found a tendency towards improved survival for women with HPV-positive vaginal cancer. Three out of four studies reporting survival according to p16 status found an improved survival among women with p16-positive vaginal cancer. For p53, only one of six studies reported an association between p53 expression and survival. Conclusions: This systematic review suggests that women with HPV- and p16-positive vaginal cancer have an improved prognosis compared with those with HPV- or p16-negative vaginal cancer. Results for p53 were varied, and no conclusion could be reached. Only 12 studies could be included in the review, of which most were based on small populations. Hence, further and larger studies on the prognostic impact of HPV, p16, and p53 in vaginal cancer are warranted.

The incidence of human papillomavirus (HPV)-associated cancers, especially those from the head and neck region, has increased. The relatively early age of presentation of HPV-positive head and neck cancer (HNC) indicates that viral infection might be acquired early in life. Persistent HPV infection has been recognized as the main risk factor for cancer development, but most studies have focused on evaluating HPV persistence in the genital region. Thus, in this work, we aimed to evaluate the prevalence of HPV in oral cavity and oropharynx in a young population, as well as the possible persistence of the infection after 12 months. Our results indicate that almost half (46.8%) of the analyzed population harbors an HPV infection either in the oral cavity or in the oropharynx. Furthermore, after 1 year of initial identification, half of them eliminated the infection, and only one person (5.26%) exhibited persistence. Interestingly, 50% of the individuals who successfully eliminated the infection acquired a new viral type, indicating that even when the primary infection is effectively eliminated by the immune system, there is a dynamic circulation of HR-HPV types that produce reinfection. This dynamic HPV infection among young individuals could influence the future establishment of cancer in some proportion of the cases. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42770-021-00602-3.

Using observational data, human papillomavirus vaccination was associated with a lower anal prevalence of vaccine-preventable types among young, sexually active gay and bisexual men soon after implementation of publicly funded vaccination programs. Supplemental digital content is available in the text., Background Starting in 2015, human papillomavirus (HPV) vaccine has been publicly funded for gay, bisexual, and other men who have sex with men (GBM) 26 years or younger in Canada. Methods Self-identified GBM who reported having sex with another man within the past 6 months were enrolled using respondent-driven sampling (RDS) between February 2017 and August 2019 in Montreal, Toronto, and Vancouver, Canada. Men aged 16 to 30 years self-collected anal specimens for HPV-DNA testing. Prevalence was estimated using RDS-II weights. We compared the prevalence of quadrivalent (HPV-6/11/16/18) and 9-valent (HPV-6/11/16/18/31/33/45/52/58) vaccine types between GBM who self-reported HPV vaccination (≥1 dose) and those reporting no vaccination using a modified Poisson regression for binary outcomes. Results Among 645 GBM who provided a valid anal specimen (median age, 26 years; 5.9% HIV positive), 40.3% reported receiving ≥1 dose of HPV vaccine, of whom 61.8% received 3 doses. One-quarter were infected with ≥1 quadrivalent type (crude, 25.7%; RDS weighted, 24.4%). After adjustment for potential confounders, vaccinated GBM had a 27% lower anal prevalence of quadrivalent types compared with unvaccinated GBM (adjusted prevalence ratio [aPR], 0.73; 95% confidence interval [CI], 0.54–1.00). Lower prevalence ratios were found among vaccinated participants who were vaccinated >2 years before enrollment (aPR, 0.47; 95% CI, 0.25–0.86) or received their first vaccine dose at age ≤23 years (aPR, 0.64; 95% CI, 0.42–0.99). Point estimates were similar for ≥2 or 3 doses and 9-valent types. Conclusions Human papillomavirus vaccination was associated with a lower anal prevalence of vaccine-preventable HPV types among young, sexually active GBM. Findings will help inform shared decision making around HPV vaccination for GBM and their healthcare providers.

Background: Uterine cervical malignancy is one of the commonly detected malignancies related to the human papillomavirus (HPV) and is increasing incidentally in developing countries. Therefore, the use of an efficient diagnostic method is required as an effectual step for cervical cancer prevention and treatment. The purpose of the study was to diagnose various types of HPV in the cervical cytology specimens in the South-East of Iran. Methods: This cross-sectional study was performed on 1079 cervical fluid cytology specimens referred for two years, between 2018-2020. Polymerase chain reaction (PCR) and hybridization (INNO-LiPA HPV Genotyping EXTRA II assay) were used to determine HPV DNA and their genotypes, respectively. Results: HPV was positive in 37.7% (407 of 1079) patients with a mean age of 34.62 ± 8.82. Among positive cases, 252 (62%) had only one HPV genotype and 155 (38.05%) had multiplex HPV genotypes, which included 94 (60.7%), 38 (24.6%), 18 (11.6%) and 5 (3.2%) cases with two, three, four and five or more genotypes, respectively. The samples with multiple strains revealed 31 HPV genotypes with the four most prevalent being HPV6 (14.7%), HPV16 (10.9%), HPV53 (9.6%) and HPV51 (5.9%). Conclusion: HPV infection is the main health challenge for women that requires improved health service programs and appropriate epidemic vaccination.

Anal high-risk human papillomavirus (hr-HPV) infection is widely considered a cause of anal cancer. However, epidemiological data are quite limited in Japan. This study investigated anal HPV infections and cytological abnormalities among MSM with or without HIV infection. Anal swabs were obtained, and cytological results were examined. Hybrid capture-based methodology was used for hr-HPV genotyping. The exclusion criterion was a history of vaccination against HPV. 644 subjects participated, and the overall prevalence of hr-HPV was 59.7% (95% CI 54.7–62.3), HIV-infected had higher prevalence than HIV-uninfected (68.9% vs 40.6%) p

The WHO has launched a global strategy to eliminate cervical cancer through the scale-up of human papillomavirus (HPV) vaccination, cervical screening, and cervical cancer treatment. Malaysia has achieved high-coverage HPV vaccination since 2010, but coverage of the existing cytology-based program remains low. Pilot studies found HPV self-sampling was acceptable and effective, with high follow-up rates when a digital registry was used, and recently the Malaysian Government announced plans for a national HPV-based screening program. We therefore evaluated the impact of primary HPV screening with self-collection in Malaysia in the context of Malaysia's existing vaccination program. We used the "Policy1-Cervix" modeling platform to assess health outcomes, cost-effectiveness, resource use and cervical cancer elimination timing (the year when cervical cancer rates reach four cases per 100 000 women) of implementing primary HPV testing with self-collection, assuming 70% routine-screening coverage could be achieved. Based on available data, we assumed that compliance with follow-up was 90% when a digital registry was used, but that compliance with follow-up would be 50-75% without the use of a digital registry. We found that the current vaccination program would prevent 27 000 to 32 200 cervical cancer cases and 11 700 to 14 000 deaths by 2070. HPV testing with a digital registry was cost-effective (CER = $US 6953-7549

OBJECTIVES We assessed the relation between clearance of high-risk human papillomavirus (HR-HPV) after large loop excision of the transformation zone (LLETZ) and absence of residual disease, in women diagnosed with cervical cancer (CC) and adenocarcinoma in situ (AIS). MATERIALS METHODS Data were collected from 92 women diagnosed with CC and AIS who were positive to HR-HPV and had a repeat cervical HPV test 3-12 weeks after LLETZ (in which CC/AIS were diagnosed) and before final surgical treatment. We compared characteristics of women with negative and positive HR-HPV after LLETZ. RESULTS The HR-HPV results after the LLETZ operation were negative in 40 women and positive in 52 women. The HR-HPV-negative group included a significantly higher incidence of AIS: 14 (35%) vs 5 (9.6%, p < .006).In the negative HR-HPV post-LLETZ group, 36 (90%) had normal histology and only 2 (5%) had cancer in the final histological specimen. Among 34 women who underwent radical hysterectomy/trachelectomy after LLETZ, a normal final histology was observed in 75% and 9% of those who were HR-HPV negative and HR-HPV positive, respectively (p < .0005). The positive predictive value for absence of residual cancer, with clearance of HR-HPV after LLETZ, was 95%. CONCLUSIONS Clearance of HR-HPV from the cervix a short time after LLETZ has a high association with the absence of residual cancer in the final outcome, either in the pathology or the follow-up. Testing for HR-HPV a short time after LLETZ might serve as a parameter for risk assessment.

This article describes a patient who developed Harada disease-like uveitis after quadrivalent human papillomavirus (HPV4) vaccination and experienced resolution without any systemic treatment. To achieve this aim, a case report and a review of related literature on HPV vaccination causing uveitis were conducted. The results of this study show a diagnosis of Harada disease-like uveitis after HPV4 vaccination based on the vaccination history, clinical symptoms, and multimodal imaging. Resolution without any systemic corticosteroid treatment was observed. According to these findings, patients may develop uveitis with Harada-like features, which can be a mild and self-limiting process, after HPV4 vaccination.

Background Human papillomavirus (HPV) is a well‐established mucosotropic carcinogen, but its impact on urothelial neoplasm is unclear. We aimed to clarify the clinical and pathological features of HPV‐related urothelial carcinoma (UC). Methods Tissue samples of 228 cases of UC were obtained from the bladder, upper and lower urinary tract, and metastatic sites to construct a tissue microarray. The samples were analyzed for the presence of HPV by a highly sensitive and specific mRNA in situ hybridization (RISH) technique (RNAscope) with a probe that can detect 18 varieties of high‐risk HPV. We also conducted immunohistochemistry (IHC) for a major HPV capsid antibody and DNA‐PCR. Results The HPV detection rates varied among the methods; probably due to low HPV copy numbers in UC tissues and the insufficient specificity and sensitivity of the IHC and PCR assays. The RISH method had the highest accuracy and identified HPV infection in 12 (5.2%) of the cases. The histopathological analysis of the HPV‐positive UC showed six cases of usual type UC, five cases of UC with squamous differentiation (UC_SqD), and one case of micropapillary UC. The HPV detection rate was six‐fold higher in the cases of UC_SqD than in the other variants of UC (odds ratio [OR] =8.9, p = 0.002). In addition, HPV infection showed a significant association with tumor grade (OR =9.8, p = 0.03) and stage (OR =4.7, p = 0.03) of UC. Moreover, the metastatic rate was higher in HPV‐positive than in negative UC (OR =3.4). Conclusion These data indicate that although the incidence of HPV infection in UC is low, it is significantly associated with squamous differentiation and poor prognosis. Furthermore, our observations show that RNAscope is an ideal method for HPV detection in UC compared with the other standard approaches such as IHC and PCR assays., The etiological role of HPV infection in urothelial carcinoma is controversial. Moreover, its clinicopathological presentation and association with squamous differentiation are still undetermined. With highly specific and sensitive mRNA in situ hybridization assay, we detected HVP in a small subset of cases associated with poor prognosis and squamous differentiation. We also showed that methodologies variance was behind the discrepancy reported in previous studies.

Background:. Cervical cancer remains a major public health issue for the Uyghur women and other women living mainly in rural areas of Xinjiang. This study aims to investigate the distribution of human papillomavirus (HPV) infection and cervical cancer in rural areas of Xinjiang, China. Methods:. Cervical cancer screening was performed on rural women aged 35 to 64 years from Xinjiang, China in 2017 through gynecological examination, vaginal discharge smear microscopy, cytology, and HPV testing. If necessary, colposcopy and biopsy were performed on women with suspicious or abnormal screening results. Results:. Of the 216,754 women screened, 15,518 received HPV testing. The HPV-positive rate was 6.75% (1047/15,518). Compared with the age 35–44 years group, the odds ratios (ORs) of HPV positivity in the age 45–54 years and 55–64 years groups were 1.18 (95% confidence interval [CI]: 1.02–1.37) and 1.84 (95% CI: 1.53–2.21), respectively. Compared with women with primary or lower education level, the ORs for HPV infection rates of women with high school and college education or above were 1.37 (95% CI: 1.09–1.72) and 1.62 (95% CI: 1.23–2.12), respectively. Uyghur women were less likely to have HPV infection than Han women, with an OR (95% CI) of 0.78 (0.61–0.99). The most prevalent HPV types among Xinjiang women were HPV 16 (24.00%), HPV 33 (12.70%), and HPV 52 (11.80%). The detection rate of cervical intraepithelial neoplasia (CIN)2+ was 0.14% and the early diagnosis rate of cervical cancer was 85.91%. The detection rates of vaginitis and cervicitis were 19.28% and 21.32%, respectively. Conclusions:. The HPV infection rate in Xinjiang is low, but the detection rate of cervical cancer and precancerous lesions is higher than the national average level. Cervical cancer is a prominent public health problem in Xinjiang, especially in southern Xinjiang.

Background This study aimed to evaluate the possible role of human papillomavirus (HPV) and Epstein–Barr virus (EBV) coinfection as an etiological factor for prostate cancer (PCa) development. Methods This case-control study was conducted on 67 patients with PCa and 40 control subjects. The expression levels of cellular and viral factors involved in inflammation, tumor progression, and metastasis were quantified, using the enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR) assay. Results The EBV/HPV coinfection was reported in 14.9% of patients in the case group and 7.5% of the control subjects. The high-risk types of HPV, that is, HPV 16 and HPV 18, were responsible for 50 and 30% of HPV/EBV-coinfected PCa cases (n = 10), respectively. No significant relationship was observed between PCa and HPV/EBV coinfection (OR = 2.9, 95% CI: 0.18–45.2, P = 0.31). However, the highest percentage of HPV genome integration was found in the HPV/EBV-coinfected PCa group (8/10; 80%). Also, the mean expression levels of inflammatory factors (IL-17, IL-6, TNF-α, NF-κB, VEGF, ROS, and RNS), anti-apoptotic mediators (Bcl-2 and survivin), and anti-anoikis factors (Twist and N-cadherin) were significantly higher in the HPV/EBV-coinfected PCa group, compared to the non-coinfected PCa cases. Nevertheless, the tumor-suppressor proteins (p53 and pRb) and E-cadherin (inhibitor of anoikis resistance) showed significant downregulations in the HPV/EBV-coinfected PCa group, compared to the non-coinfected PCa cases. Conclusion The HPV/EBV coinfection may be an etiological factor for PCa through modulation of cellular behaviors.