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Human papillomavirus (HPV), known for its oncogenic properties, is the primary cause of cervical cancer and significantly contributes to mortality rates. It also plays a considerable role in the globally rising incidences of head and neck cancers. These cancers pose a substantial health burden worldwide. Current limitations in diagnostic and treatment strategies, along with inadequate coverage of preventive vaccines in low- and middle-income countries, hinder the progress toward the World Health Organization (WHO) HPV prevention and control targets set for 2030. In response to these challenges, extensive research in structural virology has explored the properties of HPV proteins, yielding crucial insights into the mechanisms of HPV infection that are important for the development of prevention and therapeutic strategies. This review highlights recent advances in understanding the structures of HPV proteins and discusses achievements and future opportunities for HPV vaccine development. [Display omitted] In this review, Han et al. provide a comprehensive overview of HPV-related protein structures. The authors describe their roles within the HPV life cycle and discuss important protein-protein interactions. They emphasize the importance of structural biology for the development of prophylactic vaccines and therapeutics against HPV. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) infections are common among reproductive-age women. The use of primary HPV testing has proven more effective in identifying high-grade precancerous lesions, leading to better clinical outcomes in women. HPV integration into the host genome is a multifactorial process. Various host, viral, and environmental cofactors, such as smoking, cervicovaginal microbiota, estrogen levels, and coinfection with HIV, influence this process. The disruption of the E2 gene is identified as a hallmark of HPV integration and cancer development, leading to the overexpression of oncogenic proteins (E6/E7) and the formation of superenhancers, thereby contributing to cellular transformation and cervical neoplasia. HPV integration results in host genomic instability, chromosomal rearrangements, loss of function in tumor suppressor genes, and epigenome dysregulation. Countless efforts have been made to eradicate cervical cancer worldwide, including improving disease screening and human papillomavirus (HPV) vaccination programs. Nevertheless, cervical cancer still claims the lives of more than 300 000 women every year. Persistent infections with high-risk HPV genotypes 16 and 18 are the main cause of cancer and may result in HPV integration into the host genome. The central dogma is that HPV integration is an important step in oncogenesis, but in fact, it impedes the virus from replicating and spreading. HPV causing cervical cancer can therefore be perceived as a failed evolutionary viral trait. Here we outline the occurrence and mechanisms of HPV integration and how this process results in oncogenic transformation. [ABSTRACT FROM AUTHOR]

• We conducted this meta -analysis based on relevant protocols, showed a complete overview of the available data in terms of prognostic value of HPV cell-free DNA in cervical cancer. • This study demonstrated that cervical cancer patients with positive HPV cell-free DNA detection at end of treatment had significantly worse oncological outcomes compared with that of negative patients. • Personalized monitoring of HPV cell-free DNA is expected to be a promising prognostic biomarker for cervical cancer patients. This meta -analysis aimed to investigate the association between circulating human papillomavirus (HPV) cell-free DNA and oncological outcomes of cervical cancer patients. Searches were performed in MEDLINE, Embase, and CENTRAL from their inception until 26 November 2023. Inclusion criteria were: (1) pathologically confirmed cervical cancer with available HPV test results; (2) detection of HPV cell-free DNA was performed in serum/plasma before or at end of treatment; (3) studies reported oncological outcomes of cervical cancer patients according to the levels of HPV cell-free DNA. Data extraction and study quality assessment were performed independently by two authors. Pooled hazard ratios and 95% confidence intervals were calculated using the inverse-variance method for survival outcomes. Five studies were finally included in this meta -analysis. Blood samples were collected from 167 patients before treatment, with 150 individuals available for analysis at the end of treatment. Furthermore, 82 patients with available samples at 3 months post-treatment were included in the analysis. The pooled results indicated a significant association between positive HPV cell-free DNA at end of treatment and worse progression-free survival in patients with cervical cancer (pooled hazard ratio: 5.49; 95 % confidence interval: 2.85–10.58; I2: 0 %). Similar findings were observed in patients with detectable HPV cell-free DNA at 3 months post-treatment (pooled hazard ratio: 7.86; 95 % confidence interval: 3.32–18.60; I2: 0 %). However, the detection of HPV cell-free DNA before treatment was not significantly associated with progression-free survival (pooled hazard ratio: 0.97; 95 % confidence interval: 0.55–1.71; I2: 0 %). Cervical cancer patients testing positive for HPV cell-free DNA at the end of treatment or 3 months post-treatment displayed significantly poorer oncological outcomes compared to those testing negative. Thus, personalized monitoring of HPV cell-free DNA holds promise as a prognostic biomarker for patients with cervical cancer. [ABSTRACT FROM AUTHOR]

Standing orders may improve HPV vaccination rates, but clinical staff's readiness to use them has not been well-explored. We sought to explore benefits and challenges to using HPV vaccine standing orders for adolescents ages 9 to 12, understand clinical staff roles in communication about HPV vaccine, and how standing orders can reduce barriers contributing to vaccine disparities among racial and ethnic marginalized groups. Participants were a sample of 16 U.S. nurses, medical assistants, and healthcare providers working in primary care, recruited from June to September 2022. Trained staff conducted virtual, semi-structured qualitative interviews. We analyzed the resulting data using reflexive thematic analysis. Themes reflected benefits and challenges to using HPV vaccine standing orders and strategies to address clinic barriers to improve vaccine access and HPV vaccine communication. Benefits included faster and efficient clinic flow; fewer missed vaccine opportunities and promotion of early vaccination; and normalization of HPV vaccination as routine care. Challenges included possible exacerbation of existing HPV vaccine communication and recommendation barriers; and how the complexity of the vaccine administration schedule lessens nurses' and medical assistants' confidence to use standing orders. Strategies to address vaccine access barriers included using nurse-only visits to empower nurse autonomy and catch up on HPV vaccination; engaging clinical staff to follow up with overdue children; and educating parents on HPV vaccine before their child is vaccine eligible. Using HPV vaccine standing orders can promote autonomy for nurses and medical assistants and address vaccine access barriers. Clinical staff engagement and clinic support to mitigate existing vaccine communication barriers are needed to empower staff to use of HPV vaccine standing orders. [ABSTRACT FROM AUTHOR]

• The scoping review mapped self-sampling for HPV test in cervical cancer screening. • The results showed the self-sampling can be useful for cervical cancer Screening. • The results showed that self-sampling has a good patient acceptance. • The home-based procedure showed good cost-effectiveness. Cervical cancer is the third most common gynecological cancer worldwide. Its origin is linked to intraepithelial lesions caused by high-risk Human Papillomavirus (HPV) types, detected in 99.7% of cases. Early screening is essential to prevent cancer development from these lesions. Molecular methods are more specific and offer the possibility of being performed through a self-collected sample by the patient, thus contributing to increasing screening coverage for this pathology. This study aim was to map the medical-scientific literature on existing protocols for self-sampling for HPV testing in cervical cancer screening. A search strategy was developed using the following keywords and their synonyms: "self-sampling," "professional sampling," and "HPV", on the databases: MEDLINE, Cochrane Library, Virtual Health Library - BVS, Scopus, National Institute for Health Research NHS EED, Web of Science, and EMBASE. The search strategy was formulated to identify relevant studies and describe their main characteristics, such as patient acceptance of self-sampling, cost differences between the tests used, and the accuracy of self-sampling compared to the gold standard test. A total of 876 studies were found, and 33 of those studies were included in this review. Out of these, 10 studies were domized clinical trials involving 46,751 patients, and 23 observational studies included 142,795 patients. Regarding acceptance, most studies reported a preference for self-sampling. Sensitivity analyses from various studies also showed that the low cost of self-sampling kits generally increased cost-effectiveness. The study concluded that using HPV testing on self-collected samples is a viable strategy for monitoring women with HPV. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore college students' perceptions of human papillomavirus (HPV) infection and their thoughts on prevention measures. A qualitative descriptive design was used. The study adopted purposive sampling at two universities in northern Taiwan and one in central Taiwan. Twenty-six college students participated, and data saturation was reached. Content analysis was undertaken. Four main themes emerged from the data narratives: 1) having very little knowledge of HPV infection, 2) being concerned about outcomes of HPV infection, 3) taking measures to protect oneself, and 4) expecting to have HPV prevention resources. The results indicated that college students needed a more complete understanding of HPV and prevention methods to protect themselves from infection. Schools were an ideal place to provide adequate information on HPV prevention. The study suggested providing HPV-related information through school health centers and government health departments to resolve common questions and misunderstandings about HPV infection. Healthcare professionals should have a complete understanding of HPV-related knowledge in order to provide detailed information to young people. • Whether from a medical background or not, college students showed some misunderstandings about HPV infection and prevention. • The college students could take self-protection measures to prevent HPV infection but tended to ignore the risk of transmission through oral sex. • College students expected to access correct HPV prevention information from school health centers and government health departments. [ABSTRACT FROM AUTHOR]

Partnerships are fundamental to progress in immunization, and this is especially true for human papillomavirus (HPV) vaccination, which must be delivered in the context of a broader immunization, sexual and reproductive health, and cervical cancer prevention programs. Starting from the discovery and development of HPV vaccines, through to implementation and improvement of the program's resilience, partnerships have played a critical role. In May 2018, the Global Strategy to Accelerate the Elimination of Cervical Cancer set a target for 90 % of girls to be fully vaccinated with HPV vaccine by age 15 years. This will require effective partnership and multisectoral collaboration among current and future partners to ensure alignment of interests, efficient execution, and the establishment of mechanisms to resolve emerging challenges and pre-empt foreseeable risks. In ramping up this partnering approach, HPV can provide a template for other health and immunization programs. [ABSTRACT FROM AUTHOR]

Chemoradiation (CRT) may modulate the immune milieu as an in-situ vaccine. Rapid dose delivery of brachytherapy has unclear impact on T-cell repertoires. HPV-associated cancers express viral oncoproteins E6/E7, which enable tracking antigen/tumor-specific immunity during CRT. Thirteen cervical cancer patients on a multi-institutional prospective protocol from 1/2020–1/2023 underwent standard-of-care CRT with pulsed-dose-rate brachytherapy boost (2 fractions). Cervix swabs at various timepoints underwent multiplex DNA deep sequencing of the TCR-β/CDR3 region with immunoSEQ. Separately, HPV-responsive T-cell clones were also expanded ex vivo. Statistical analysis was via Mann-Whitney-U. TCR productive clonality, templates, frequency, or rearrangements increased post-brachytherapy in 8 patients. Seven patients had E6/E7-responsive evolution over CRT with increased productive templates (ranges: 1.2–50.2 fold-increase from baseline), frequency (1.2–1.7), rearrangements (1.2–40.2), and clonality (1.2–15.4). Five patients had HPV-responsive clonal expansion post-brachytherapy, without changes in HPV non-responsive clones. Epitope mapping revealed VDJ rearrangements targeting cervical cancer-associated antigens in 5 patients. The only two patients with disease recurrence lacked response in all metrics. A lack of global TCR remodeling correlated with worse recurrence-free survival, p = 0.04. CRT and brachytherapy alters the cervical cancer microenvironment to facilitate the expansion of specific T-cell populations, which may contribute to treatment efficacy. [ABSTRACT FROM AUTHOR]

Misinformation, disinformation, and conspiracy theories about vaccines are key drivers of vaccine hesitancy. A repeated false claim about COVID-19 vaccines is that the vaccines cause female infertility. Dating back decades, various conspiracy theories have linked vaccination programs with infertility and thus harmed vaccination programs in Africa, Asia, and Central America, particularly against polio and tetanus. In the United States, Europe, and Australia, human papilloma virus (HPV) vaccines have been falsely blamed for infertility and primary ovarian insufficiency (POI). After distribution of COVID-19 vaccines began in December 2020, almost immediately there arose conspiracy theories claiming that these vaccines cause menstrual irregularities, miscarriages, and infertility, promoted by noted antivaccine activists Robert F. Kennedy, Jr. and Andrew Wakefield among others. Here we will explore the history of this antivaccine narrative, how it has been promulgated in the past and repurposed to COVID-19 vaccines, and strategies to counter it. [ABSTRACT FROM AUTHOR]

Cervical cancer causes more than 300,000 deaths worldwide every year, affecting women from a young age. It has a well-understood natural history, caused by HPV, which is estimated to be responsible for 99.8% of cases. In order to decrease the number of UK cervical cancer cases, a national screening programme was launched in 1988. Women between the ages of 25 and 64 are invited for cervical screening. A primary high-risk HPV testing approach is used, whereby samples are only tested for cytology if they are positive for high-risk HPV. The national HPV vaccination programme was introduced in 2008 in the UK. The Gardasil 9 vaccine is offered at year 8 in UK schools (ages 12–13 years old) to boys and girls. These programmes have been a huge success in reducing the number of cervical cancer cases. However, still only 70% of eligible women attend their screening appointments. To further increase the proportion of women reached by the programme, further alternatives are currently tested, including home vaginal swab tests and urinary HPV testing. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) vaccines are offered free of charge in Finland to 10–12-year-old children. Nationally about 80% of girls are vaccinated, with regional differences in first dose coverage varying from 62% to 82% in girls born in 2011. This study examined the factors associated with HPV vaccination intention. Furthermore, we assessed the realisation of HPV vaccination among the daughters of the participating parents. A web-based survey was conducted for randomly selected parents of girls (N = 6 465) aged 10 to 14 years of age. Data was collected in February and March 2022 in five Finnish high and low coverage municipalities. The national vaccination register was employed to assess realisation of vaccination. Participation rate was 13.7% (n = 883 parents). Almost all parents were aware of the association between HPV and cervical cancer, but only one fifth was aware of other diseases associated with HPV. Adherence to the national vaccination programme, parents' mother tongue, and trusting in official information were associated with positive vaccination intention. The most often reported reason for non-vaccination was fear of adverse effects (22%). Overall, parental attitudes towards HPV vaccination were positive, with 83% of parents indicating their daughter had received or will receive the vaccination. Vaccination realisation was subsequently examined and 88% of the daughters were vaccinated. Despite low knowledge of HPV-related diseases overall, majority of parents held a positive intention to vaccinate their daughter. Realisation of intention was high in our study, higher than the national uptake. Foreign-origin parents had lower intention to vaccinate their daughters. As information on HPV and its vaccine is available in 11 languages, there is a need to re-think accessibility. In-depth interviews are needed to better explore the reasons behind non-vaccination. [ABSTRACT FROM AUTHOR]

Compared to oropharyngeal squamous cell carcinoma (SCC), the association between p16 status and outcome in non-oropharyngeal head and neck squamous cell carcinoma (HNSCC) is less clear. We conducted this single-institutional study to evaluate the prognostic value of p16 status in this population. A retrospective review was conducted for all newly diagnosed non-metastatic HNSCC arising from larynx, hypopharynx, sinonasal mucosa, and oral cavity tested for p16 and treated with curative intent between Jan 2009 and December 2021 in our institution. p16 immunohistochemistry (IHC) staining was routinely performed in laryngeal and hypopharyngeal cancer during 2014 and 2017 for EORTC1219 trial eligibility, and for selected non-oropharyngeal HNSCC if the patients were non-smokers/non-drinkers, or if tumours were non-keratinizing or of basaloid morphology. All p16 IHC was performed and interpreted at our institution by experienced head and neck pathologists. p16 positivity was defined by diffuse cytoplasmic and nuclear staining in >70% tumour cells. A proportion of tumours was also tested for HPV DNA by polymerase chain reaction (PCR). Overall survival (OS), disease-free survival (DFS), locoregional control (LRC) and distant control (DC) were compared between p16-positive and p16-negative cohorts. Multivariable analysis was performed to evaluate the prognostic value of tumour p16 status on OS. Of 3176 consecutive non-oropharyngeal HNSCC, p16 was tested in 466 (15%) patients, of whom 91 (20%) were p16-positive (26 larynx, 20 hypopharynx, 35 sinonasal tract, and 10 oral cavity) and 375 (80%) were p16-negative (162 larynx, 67 hypopharynx, 31 sinonasal tract, and 115 oral cavity). PCR for HPV DNA was performed in 39 p16-positive and 28 p16-negative cases and revealed 100% concordance between p16 IHC and HPV DNA. The most common HPV genotypes were single infection HPV-16 (69.2%), single infection HPV-18 (10.3%), co-infection HPV 16 & 18 (2.6%), co-infection HPV 16 & 51 (2.6%) and other HPV genotypes (15.4%). The median age of patients tested was 62.5 years (range 54.5-70.5). Patients with p16-positive tumour had lower smoking pack-years compared to patients with p16-negative tumour (median 12.5 vs 30, p<0.001). There was no difference in TNM-8 T-category (p=0.09) and N-category (p=0.20) distribution between the two cohorts. Sinonasal primary site had the highest p16-positive rate (35/66, 53%), followed by hypopharynx (20/87, 23%), larynx (26/188, 14%), and oral cavity (10/125, 8%). Median follow up was 4.6 years (range 0.2-13.2). p16-positive non-oropharyngeal HNSCC had higher 5-year OS (80% vs 58%, p<0.001), DFS (73% vs 48%, p<0.001), LRC (89% vs 75%, p=0.003), and DC (91% vs 80%, p=0.007) vs p16-negative. Multivariable analysis, adjusting for primary disease site, age, smoking history, TNM-8 T-categories, N-categories, and use of systemic therapy, confirmed the prognostic importance of p16-positivity on OS (adjusted hazard ratio 0.46, 95% confidence interval 0.28 to 0.75, p=0.002). Sub-site analysis revealed p16-positive laryngeal and hypopharyngeal SCCs had higher 5-year OS (larynx: 89% vs 63%, p=0.015; hypopharynx: 77% vs 35%, p=0.003); and DFS (larynx: 85% vs 52%, p=0.004; hypopharynx: 67% vs 24%, p<0.001) vs p-16 negative counterparts. A non-significant trend toward better 5-year OS (82% vs 42%, p=0.051) and DFS (75% vs 42%, p=0.054) were observed in p16-positive sinonasal SCCs. However, no difference in OS (57% vs 66%, p=0.852) and DFS (50% vs 56%, p=0.906) was observed in p16-positive versus p16-negative oral cavity SCC (Table 1). [Display omitted] In this selected cohort of non-oropharyngeal HNSCC, p16-positive status carries a survival advantage (HR 0.46) which is similar to the 0.49 HR of HPV-positive status reported in RTOG 0129 (Ang et al. 2010) for oropharyngeal carcinoma. This 5-year OS difference is mainly seen in laryngeal (26% absolute OS difference) and hypopharyngeal (42% absolute OS difference) SCC, possibly in sinonasal SCCs, but not in oral cavity SCC. The association of p16 and HPV, as well as its prognostic value should be confirmed in large systematically tested datasets. [ABSTRACT FROM AUTHOR]

Local ablation of oligometastases has been shown to improve patient survival (1). Oligometastases are more frequent in viral-related head and neck squamous cell carcinomas (HNSCC) compared to non-viral HNSCC, with lung as the most common site (2). We reviewed patients with HPV-positive (+) HNSCCs who developed lung metastases, and report outcomes for all patients, focusing on those receiving definitive intent local ablation. We reviewed all HPV(+) HNSCCs patients who developed distant metastases (DM) to lung ± other organs after definitive radiotherapy or chemoradiotherapy at our institution from January 2003 to December 2021. DM in lung were further classified as oligometastases (≤5 lesions) vs polymetastases. Among those patients classified as oligometastases, we pragmatically sub-staged according to the American Joint Commission on Cancer 8th edition for primary non-small cell lung cancer (NSCLC) (3) (oligometastasis mimicking the behavior of NSCLC) to assess differences in outcome after local ablative therapy. Oligometastases in lung were confirmed by p16(+) staining to rule out lung primary when possible. Definitive intent local ablation (LA) was defined as either surgical resection or definitive-intent [EQD2 ≥40 Gy; alpha/beta=10 Gy] (chemo)radiation. Overall survival (OS) and progression free survival (PFS) after lung metastases were estimated by Kaplan Meier curves, with log rank test for outcome comparison. Of 1908 consecutive patients treated during the study period, 170 (9%) developed DM to lung and other sites. Lung was the only DM site in 79 patients (4%), of whom, 20 (1%) had oligometastases and underwent LA: 15 underwent surgery (1 lobectomy, 2 segmentectomies, 12 wedge resections), 1 surgery + radiation, 3 radiation alone and 1 chemoradiation. Median follow-up was 2.0 years (range 0-13.5). For OM patients receiving LA, OS at 3 and 5 years after detection of metastasis was 69% and 57%; PFS was 40% at 3 years and 34% at 5 years. When patients who developed isolated lung metastases were staged as per the TNM 8th edition for lung cancer, most patients were N0 (n=16) and early stage. Some patients with N+ disease (n=4) or very advanced T category disease (T4, n=1) were treated with definitive intent as well. OS of oligometastatic lung DM treated with local ablative treatment according to lung cancer N stage showed 75% at 3 years and 75% at 5 years for N+ disease, and 67% at 3 years and 50% at 5 years for N0 disease (p = 0.587). PFS of oligometastatic lung DM treated with ablative treatment according to lung cancer N stage was not statistically different with 25% at 3 years and 25% at 5 years for N+ disease, and 44% at 3 years and 36% at 5 years for N0 disease (p = 0.678). For comparison, across all 170 patients with DM to lung and other sites, OS at 3 and 5 years after detection was 22% and 16%. For the 150 patients who did not receive LA, these rates were 15% and 10% respectively. For the 79 with lung-only DM who did not receive LA, these rates were 21% and 16% respectively. These were statistically different compared to OS at 3 and 5 years for OM patients receiving LA (p < 0.001). [Display omitted] Patients with oligometastatic HPV(+) HNSCC to lung treated with local ablation with definitive intent have significantly longer OS compared to those with polymetastatic disease who had palliative treatment or best supportive care treatment. Isolated lung lesions, large lung lesions, and lung lesions with nodal involvement treated with definitive intent all showed substantially longer OS compared with patients who did not receive ablative therapy. Isolated pulmonary DM in patients with HPV(+) HNSCC should be considered for local ablation with definitive intent. [ABSTRACT FROM AUTHOR]

• This study reports HPV prevalence in young females following over ten years of high coverage HPV vaccination in England. • Dramatic declines were observed in HPV vaccine-type and closely related type prevalence in vaccine eligible females. • Findings showed no indication of type-replacement. • These findings enable confidence in planning for cervical screening, and in predicting declines in HPV-related cancers. The UK national human papillomavirus (HPV) vaccination programme was introduced in 2008 using the bivalent HPV16/18 vaccine, changing to the quadrivalent HPV6/11/16/18 vaccine from 2012. We provide an analysis of type-specific HPV prevalence in young sexually active females in England to end 2020 (when the first routinely HPV vaccinated females were reaching 25 years of age and entering the National Health Service Cervical Screening Programme), showing the impact of over ten years of high coverage HPV vaccination. Residual vulvovaginal swabs (VVS) were collected from 16 to 24 year old women attending for chlamydia screening between 2010 and 2020, anonymised and tested for type-specific HPV DNA. Trends in vaccine and non-vaccine HPV type prevalence were compared over time and association with vaccination coverage was evaluated within the post-vaccination period. A total of 21,168 eligible VVS specimens were tested for HPV DNA. The prevalence of HPV16/18 in sexually active 16–18 year old females who were offered vaccination aged 12–13 years was <1% in the most recent years tested, compared to over 15% prior to the vaccination programme in 2008. The magnitude of these decreases also suggests reduced transmission is offering some herd protection to unvaccinated females. HPV31/33/45 prevalence also steadily decreased, providing evidence of cross-protection. HPV6/11 prevalence remained stable during the bivalent vaccine period, with more recent declines, as expected due to the use of the quadrivalent vaccine. There has been no substantive increase in the prevalence of other high-risk (HR) HPV types. More than ten years of high coverage HPV vaccination in adolescent females in England has delivered dramatic declines in the prevalence of HPV vaccine-types and closely related HPV types in females in the vaccine eligible age group, and no indication of type replacement. These findings should enable confidence in planning for cervical screening of these females, and in predicting declines in HPV-related cancers. [ABSTRACT FROM AUTHOR]

Individuals with human papillomavirus (HPV)-related disease remain at risk for subsequent HPV infection and related disease after treatment of specific lesions. Prophylactic HPV vaccines have shown benefits in preventing subsequent HPV-related disease when administered before or soon after treatment. Based on our understanding of the HPV life cycle and vaccine mechanism of action, prophylactic HPV vaccination is not expected to clear active persistent HPV infection or unresected HPV-associated dysplastic tissue remaining after surgery. However, vaccination may reasonably be expected to prevent new HPV infections caused by a different HPV type as well as re-infection with the same HPV type, whether from a new exposure to an infected partner or through autoinoculation from an adjacent or distant productively infected site. In this review, we describe the evidence for using prophylactic HPV vaccines in patients with HPV-associated disease before, during, or after treatment and discuss potential mechanisms by which individuals with HPV-associated disease may or may not benefit from prophylactic vaccines. We also consider how precise terminology relating to the use of prophylactic vaccines in this population is critical to avoid the incorrect implication that prophylactic vaccines have direct therapeutic potential, which would be counter to the vaccine's mechanism of action, as well as considered off-label. In other words, the observed effects occur through the known mechanism of action of prophylactic HPV vaccines, namely by preventing virus of the same or a different HPV type from infecting the patient after the procedure. [ABSTRACT FROM AUTHOR]

Cancer screening can play an important role in early detection, improving treatment outcomes and reducing morbidity and mortality. Breast and cervical cancers belong to the most common gynaecological cancers group. Countries provide different screening programmes on its eligible population basis centred on different health care policies. This scientific study aims to assess and understand the health inequalities in the member countries of the European Board & College of Obstetrics and Gynaecology (EBCOG) as regards screening programmes of gynaecological cancer, with a special focus on breast and cervical cancers' screening strategies. A descriptive questionnaire-based study was conducted, addressed to EBCOG member countries. Ninety-one percent of the countries have an organized national or regional screening programme for cervical cancer. Of these, 45% of countries use both cytology and testing for Human Papilloma Virus (HPV) as screening test, 31% use cytology exclusively and 17% only perform HPV testing. Considerable differences were found regarding the interval of screening test: there are countries performing HPV detection triennially, while others perform only conventional cytology every 5 years. Sixty-nine percent of countries included in this study begin screening for cervical cancer in women aged 25 to 29 years, four of them using HPV detection as the screening test. Six countries begin cervical cancer screening before the age of 25. As regards vaccination against HPV, almost all countries have implemented national HPV vaccination programme, except in Poland and Turkey. The 9-valent HPV vaccine is the most frequently offered (77% of countries) and the majority vaccination programmes include both girls and boys. As regards breast cancer screening, all thirty-two countries have an implemented screening programme. All countries perform mammography as the screening test, 62.5% of them begin in women aged 50 to 54, with a 2-yearly interval in the majority. In five countries, screening programmes are performed biennially, starting between 45 and 49 years old. Seven countries start in women aged 41 to 44. There are discrepancies around gynaecological cancer screenings provision among EBCOG member countries. It is important to establish European recommendations about screening for gynaecological cancers, in order to standardize the access to equitable better health care in gynaecological cancers within Europe. [ABSTRACT FROM AUTHOR]

The Healthy People 2030 goal is for 80% of all adolescents to complete their HPV vaccination series. Per the 2021, National Immunization Survey-Teen (NIS-Teen), 61.7% of adolescents have completed the series, and Indiana lags below the national average (55.2%). The present study estimated the 2-dose HPV vaccine series completion rates across Indiana counties among individuals aged 9–14 years who received their first dose of vaccine and determined what factors were associated with series completion at the county level. The association of county-level sociodemographic and health measures with series completion was also examined. Data were extracted from the Indiana Immunization Information System (IIS), administered by the Indiana Department of Health. All vaccine providers are required to report all immunizations to the system for any patient under age 19 years. All Indiana children ages 9–14 years at the time of first dose who had initiated HPV vaccination in 2017 or 2018 were included. Two-dose series completion was evaluated through October of 2020, allowing a minimum gap of 22 months from first dose administration. All statistical analyses were conducted at the county-level. The Indiana HPV vaccination series completion rate among individuals that received the first dose was on average 73% across counties, ranging from 55.7% to 90.4%. Higher series completion was positively associated with primary care providers per capita, participation in mammography screening among Medicare enrollees, median household income, life expectancy, percentage of residents with some college, percentage of adults up-to-date with colonoscopy screening, and percentage of adults with flu vaccine. There was wide variability in series completion across Indiana counties. HPV series completion was associated with county-level sociodemographic and health measures, particularly variables reflecting difficulties with access to care and lack of financial resources. [ABSTRACT FROM AUTHOR]

• Expression pattern of complement regulatory proteins (CRPs) CD46, CD59, and CD55 in HPV-positive (HPV +) & negative (HPV-) cervical cancer cell lines. • A differential expression profile of CRPs in HPV+ and HPV- cervical cancer cell lines. • A high level of CD59 expression in Hela cells and SiHa cells but low expression in HPV- C33a cells. • CRPs may serve as potential early diagnostic and immune-modulatory markers for HPV-infected cervical cancer. This study aimed to evaluate the expression pattern of complement regulatory proteins (CRPs) CD46, CD59, and CD55 in HPV-positive (HPV+) & negative (HPV-) cervical cancer cell lines in search of a reliable differential biomarker. We analysed the expression of CRPs in HPV 16-positive SiHa cell line, HPV 18-positive HeLa cell line, and HPV-negative cell line C33a using RT-qPCR, Western blotting, flow cytometry, and confocal microscopy. We observed a differential expression profile of CRPs in HPV+ and HPV- cervical cancer cell lines. The mRNA level of CD59 & CD55 showed a higher expression pattern in HPV+ cells when compared to HPV- cancer cells. However, flow cytometry-based experiments revealed that CD46 was preferentially expressed more in HPV 16-positive SiHa cells followed by HPV 18-positive HeLa cells when compared to HPV- C33a cells. Interestingly, confocal microscopy revealed a high level of CD59 expression in Hela cells and SiHa cells but low expression in HPV- C33a cells. In addition, HPV 18-positive HeLa cells expressed more CD55, which was lower in SiHa cells and very weak in C33a cells. The study demonstrates the differential expression of CRPs in both HPV+ and HPV- cervical cancer cells for the first time, and their potential to serve as an early diagnostic marker for cervical carcinogenesis. [ABSTRACT FROM AUTHOR]

• Immunisation nurses (IMNs) feel that HPV education for 15–17 year olds is important. • IMNs are highly motivated to design and deliver HPV education for adolescents. • IMNs are experts in HPV education and feel their skills are underutilized. • IMN barriers include time, resources, parental attitudes and teacher training. • Further collaboration between the PHA and the EA is key to IMN's role development. Human Papilloma Virus (HPV) is responsible for the development of cervical, vaginal, vulvar, penile, oropharyngeal and anal cancers. Throughout the UK, Immunisation nurses (IMNs) deliver school-based HPV vaccinations to students 12–13 years old. Providing HPV education to 15–17 year old students may promote decision-making regarding their sexual health and award opportunity for unvaccinated students to self-consent to the vaccination. This study aims to explore the perceptions of IMNs regarding the value of providing HPV education to 15–17 year old students and to explore whether IMNs feel that the design/delivery of this education should form part of their professional role. Six focus groups were conducted online with IMNs from all five Health and Social Care Trusts in Northern Ireland, UK, between January-June 2021. Data were analysed using the COM-B model to identify factors that might influence IMNs' behaviour towards designing/delivering this education for 15–17 year old students. IMNs were highly motivated to design and deliver this HPV education. Facilitators promoting this behaviour included their specialist training, their previous sexual health teaching experience and their desire to educate young people. Barriers negatively influencing this behaviour included lack of time/resources, parental influences, lack of school support and lack of teaching/presentation skills training. IMNs feel that they are the most appropriate professionals to design/deliver HPV education for 15–17 year old students. National policy change, based on collaboration between the Public Health Agency and Education Authority, is a key factor in facilitating IMNs to implement this school-based HPV education intervention. [ABSTRACT FROM AUTHOR]

To investigate the role of NRF2 signalling in conferring superior prognosis in patients with HPV positive (HPV+ve) head & neck squamous cell carcinomas (HNSCC) compared to HPV negative (HPV−ve) HNSCC and develop molecular markers for selection of HPV+ve HNSCC patients for treatment de-escalation trials. NRF2 activity (NRF2, KEAP1 , and NRF2-transcriptional targets), p16, and p53 levels between HPV+ve HNSCC and HPV−ve HNSCC in prospective and retrospective tumor samples as well as from TCGA database were compared. Cancer cells were transfected with HPV-E6/E7 plasmid to elucidate if HPV infection represses NRF2 activity and sensitizes to chemo-radiotherapy. Prospective analysis revealed a marked reduction in expression of NRF2, and its downstream genes in HPV+ve tumors compared to HPV−ve tumors. A retrospective analysis by IHC revealed significantly lower NQO1 in p16high tumors compared to p16low tumors and the NQO1 expression correlated negatively with p16 and positively with p53. Analysis of the TCGA database confirmed low constitutive NRF2 activity in HPV+ve HNSCC compared to HPV−ve HNSCC and revealed that HPV+ve HNSCC patients with 'low NQO1' expression showed better overall survival compared to HPV+ve HNSCC patients with 'high NQO1' expression. Ectopic expression of HPV-E6/E7 plasmid in various cancer cells repressed constitutive NRF2 activity, reduced total GSH, increased ROS levels, and sensitized the cancer cells to cisplatin and ionizing radiation. Low constitutive NRF2 activity contributes to better prognosis of HPV+ve HNSCC patients. Co-expression of p16high, NQO1low, and p53low could serve as a predictive biomarker for the selection of HPV + ve HNSCC patients for de-escalation trials. [Display omitted] • HPV + ve head and neck tumors are associated with lower constitutive NRF2 activity compared to HPV−ve head and neck tumors. • Ectopic expression of HPV-E6/E7 downregulated NQO1 activity and decreased total GSH levels. • Ectopic expression of HPV-E6/E7 repressed NRF2 activation and enhanced sensitivity to cisplatin and ionizing radiation. • p16high/NQO1low/p53low can be a predictive biomarker for selecting HNSCC patients for treatment de-escalation. [ABSTRACT FROM AUTHOR]

Human Papillomavirus (HPV) persistence leads to the chronification of cervical inflammation, where HLA-G and Foxp3; immunomodulatory molecules, may contribute to the aggravation of the lesion and cancerization. Here, we evaluated the synergic effect of these two molecules in the worsening of the lesion in presence of HPV infection. Hundred and eighty (180) women cervical cells and biopsies were collected for (i) HLAG Sanger sequencing and gene expression, and (ii) HLA-G and Foxp3 molecule expressions by immunohistochemistry. 53 women were HPV+ against 127 women HPV−. HPV+ women were more at risk of having cytological changes (p ≤ 0.0123), histological changes (p < 0.0011), and cervical lesion (p = 0.0004). The HLA-G + 3142CC genotype predisposed women to infection (p = 0.0190), while HLA-G + 3142C and +3035 T alleles were associated with HLA-G5 transcript expression. Both sHLA-G (p = 0.030) and Foxp3 (p = 0.0002) proteins were higher in cervical lesion as well as in high-grade lesion. In addition, sHLA-G+ cells were positively correlated to Foxp3+ cells in presence of HPV infection and in cervical grade II/III injuries. In conclusion, HPV may use HLA-G and Foxp3 as a way of host immune escape contributing to the persistence of infection and inflammation, leading to the cervical lesion and the worsening of lesions. [ABSTRACT FROM AUTHOR]

Previous studies have suggested a protective effect of male circumcision on human papillomavirus (HPV) infections in males, and that this protection may be conferred to their female sexual partners. To synthesize the available evidence on the association between male circumcision and HPV infections in males and females. We searched MEDLINE, Embase, Scopus, Cochrane, LILACS, and ProQuest Dissertations & Theses Global for records published up to 22 June 2022. We considered observational and experimental studies that assessed male circumcision status and HPV prevalence, incidence, or clearance in males or females for inclusion. Males and their female sexual partners who were tested for genital HPV infection. Male circumcision compared with no circumcision. The Newcastle-Ottawa scale was used for observational studies, and the Cochrane risk-of-bias tool was used for randomized trials. We estimated summary measures of effect and 95% CIs for the prevalence, incidence, and clearance of HPV infections in males and females using random-effects meta-analysis. We assessed the effect modification of circumcision on HPV prevalence by the penile site in males using random-effects meta-regression. Across 32 studies, male circumcision was associated with decreased odds of prevalent HPV infections (odds ratio, 0.45; 95% CI, 0.34–0.61), a reduced incidence rate of HPV infections (incidence rate ratio, 0.69; 95% CI, 0.57–0.83), and an increased risk of clearing HPV infections (risk ratio, 1.44; 95% CI, 1.28–1.61) at the glans penis among male subjects. Circumcision conferred greater protection against infection at the glans than the shaft (odds ratio, 0.68; 95% CI, 0.48–0.98). Females with circumcised partners were protected from all outcomes. Male circumcision may protect against various HPV infection outcomes, suggesting its prophylactic potential. Understanding the site-specific effects of circumcision on HPV infection prevalence has important implications for studies of HPV transmission. [ABSTRACT FROM AUTHOR]

Human papilloma virus (HPV)-associated oropharyngeal squamous cell carcinoma is the most common HPV-associated head and neck carcinoma. It is biologically unique and has a better prognosis than HPV-independent squamous cell carcinoma. The most common histomorphology of HPV-associated oropharyngeal squamous cell carcinoma is nonkeratinizing basaloid form of squamous cell carcinoma. Head and neck squamous cell carcinomas clinically often present as a neck mass and cytological sample obtained by fine needle aspiration is a crucial part of diagnostic work-up and it can be the only diagnostic material available. Several cytological samples including direct smears, cytospins, cell blocks and liquid-based material can be used for p16 immunohistochemistry, high-risk (hr) HPV DNA in situ hybridization (ISH), E6/E7 hrHPV RNA ISH, and hrHPV polymerase chain reaction. Quality control issues must be considered in all detection methodologies applied in cytological material. The selection of method depends on material type, turnaround time, standardization, sensitivity, and specificity. p16 immunohistochemistry should be applied and interpreted in conjunction with squamous cell morphology and caution should arise in cases with unusual morphology. p16 positivity alone is not recommended as a diagnostic indicator. [ABSTRACT FROM AUTHOR]

Introduction: Solid organ transplant recipients (SOTRs) are susceptible to various dermatological complications caused by long-term immunosuppressive therapy. Of these complications, viral infections are noteworthy because of their high prevalence and the potential morbidity associated with viral carcinogenesis. Objectives: To evaluate the occurrence of cutaneous viral infections in SOTRs and their correlation with clinical features, transplant type, and the length and intensity of immunosuppressive therapy. Methods: This retrospective cohort study included SOTRs followed up at the Department of Dermatology in a tertiary hospital. The outcomes analyzed were the occurrence of cutaneous viral infections, including human papillomavirus (HPV) infection, herpes simplex, herpes zoster, molluscum contagiosum, Merkel cell carcinoma, Kaposi's sarcoma, and cytomegalovirus, and the occurrence of HPV-related neoplasms. Clinical variables, such as length and intensity of immunosuppression, type of transplanted organ, and comorbidities, were analyzed as possible risk factors for cutaneous viral infections in SOTRs. Results: A total of 528 SOTRs were included in this study, among which 53.8% had one or more viral infections. Of these, 10% developed a virus-associated malignancy (HPV-associated carcinoma, Merkel cell carcinoma, or Kaposi's sarcoma). The higher risk of viral infections among SOTRs was associated with cyclosporine intake (1.40-fold higher risk) and younger age at transplantation. The use of an immunosuppressive regimen, including additional drugs, was associated with a higher risk of genital HPV infection (1.50-fold higher risk for each incremental drug). Conclusions: The occurrence of cutaneous viral infections in SOTRs is directly associated with the duration and intensity of immunosuppressive therapy. Patients at higher risk were those taking drugs with a stronger impact on cellular immunity and/or those on an immunosuppressive regimen comprising various drugs. [ABSTRACT FROM AUTHOR]

In Reunion Island, papillomavirus (HPV) vaccination coverage is low. A study encouraging vaccination in middle school showed low rate of participation. The main objective of the study was to understand barriers and motivations to HPV vaccination in populations yet sensitized to its benefits. The study focused on population around the intervention school where a health promotion program was conducted during school year 2020–2021. Semi-structured face-to-face interviews among children, children's parents, school staff, general practitioners (GP) and association members were conducted. A qualitative study was adopted using a grounded theory approach to obtain an in-depth understanding of issues pertaining to HPV vaccination. A total of 19 school staff members, 20 parents of middle school children, 39 children, 5 GPs and 3 association members were interviewed in May 2021. Anti-vaccination attitudes included: fear of serious adverse effects (such as fertility) due to poor knowledge, fear of encouraging sexuality among teenagers, mistrust towards scientists and the pharmaceutical industry and the negative impact from social networks. However, we found that the influence of the school, GP's and 'story-telling' study testimonials were crucial to invert the balance and motivate children's vaccination. Reproductive adverse events related to the HPV vaccine may be strongly perceived amongst our population, either regarding fertility or negative fetal effects; though Reunion island has 5% of pregnancies among teenagers. It is crucial to lift this taboo related to sexuality and encourage dialogue between children and their close social network. This better understanding of barriers and motivations will help us increase the impact of school-based HPV vaccination, which will be introduced in September 2023 in whole France. [ABSTRACT FROM AUTHOR]

The human papillomavirus (HPV) causes genitourinary and oropharyngeal cancers. The HPV vaccine is safe and effective in preventing those diseases; however, vaccine series completion rates remain low in the United States. Our quality improvement (QI) project aimed to increase HPV-vaccination series completion rates to 70% from 2017 to 2020 for the 13-year patient population in an extensive academic pediatric primary care network that serves predominantly minority and Medicaid-insured children in Columbus, OH. The outcome measure was the percentage of 13-years Nationwide Children's Hospital Primary Care Network patients who completed the two-dose vaccine series by their 13th birthday. Four QI implemented interventions were utilized. Electronic medical records alert informed providers when the HPV vaccines are due. We studied monthly data for the network and for individual clinics using statistical process control, displaying data on a control chart. We followed two process measures, captured opportunity rate, and the number of HPV vaccines given. We substantially increased HPV-vaccination series completion rates overall in the 13-year teen population from 27% to 65%, and three clinics reached the 70% goal for at least one quarter. Latino children had the highest completion rate of 80% and White children had the lowest completion rate at 64%. Our QI project used four measures to improve HPV-vaccination series completion rates in the 13-year patient population that serves minority and low-income teens predominantly. Further QI studies are needed to improve HPV vaccine completion rates in teens. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) causes a serious socioeconomic burden globally. However, there is currently no consensus on the optimal sampling method for HPVDNA genotyping in circumcised heterosexual men. This study aimed to determine the diagnostic efficacy of 6 different anatomic sampling sites in HPV DNA polymerase chain reaction (PCR) testing of circumcised heterosexual men with genital warts. The study included circumcised heterosexual men who presented to our clinic with complaints of genital warts. Swab samples were obtained from the penile shaft (PS), scrotum, coronal sulcus (CS), and external urethral meatus (EUM). First-void urine (FVU) and genital wart biopsy (GWB) were also tested for HPV DNA by PCR. A total of 32 patients (mean age: 36.9 ± 6.9 years) were included. None of the six samples studied was sufficient on its own to reveal all HPV types detected in a patient. When the samples were analyzed individually, GWB detected an average of 49.5% of total HPV types in a patient. This rate was 50.5% for PS, 40.4% for CS, 31.6% for scrotum, 26.3% for EUM, and 15.8% for FVU samples. The detection rate increased to 75.8% with combined testing of GWB and PS samples, 83.2% with GWB/PS/CS, 90.5% with GWB/PS/CS/scrotum, and 98.9% with GWB/PS/CS/scrotum/EUM samples. No single anatomic region or sample type can detect all HPV types present in circumcised heterosexual men by PCR assay. The detection rate approaches 99% when wart biopsy is combined with swab sampling of the penile shaft, coronal sulcus, scrotum, and external urethral meatus. [ABSTRACT FROM AUTHOR]

To investigate T cell immunoreceptor with Ig and ITIM domain (TIGIT), V-domain Ig suppressor of T cell activation (VISTA), and lymphocyte-activation gene-3 (LAG-3) expression in pathological tissue of human papillomavirus (HPV)-infected cervical cancer (CC) patients and their relationship with patient prognosis. Clinical data of 175 patients with HPV-infected CC were collected retrospectively. Tumor tissue sections were stained immunohistochemically for TIGIT, VISTA, and LAG-3. The Kaplan-Meier method calculated patient survival. Univariate and multivariate Cox proportional hazards models analyzed all potential risk factors for survival. When combined positive score (CPS)= 1 was used as the cut-off value, the Kaplan-Meier survival curve showed that the progression-free survival (PFS) and overall survival (OS) of patients with positive expression of TIGIT and VISTA are shorter (both p < 0.05). Univariate COX regression analysis showed that the positive expression of TIGIT and VISTA are related to patient PFS and OS (both HR>1.0 and p < 0.05). Multivariate COX regression analysis showed that TIGIT-positive patients had shorter OS and VISTA-positive patients had shorter PFS (both HR>1.0 and p < 0.05). There is no significant correlation between LAG-3 expression and PFS or OS. When CPS= 10 was used as the cut-off value, Kaplan-Meier survival curve showed that TIGIT-positive patients had shorter OS (p = 0.019). Univariate COX regression analysis showed that TIGIT-positive expression was associated with the OS of patients (HR=2.209, CI: 1.118–4.365, p = 0.023). However, multivariate COX regression analysis showed that TIGIT expression was not associated significantly with OS. There was no significant correlation between VISTA and LAG-3 expression and PFS or OS. TIGIT and VISTA are associated closely with HPV-infected CC prognosis and are effective biomarkers. [ABSTRACT FROM AUTHOR]

Cervical cancer is considered the most common human papillomavirus (HPV)–associated disease in women. Primary and secondary prevention methods have been established through Pap tests, HPV molecular testing, and vaccines. Although the most common high-risk HPV (HR-HPV) genotypes in the United States are 16, 18, and 45, there is reported ethnic disparity in the distribution of these genotypes. Data analysis of HPV genotype results on cervical pap tests in our institution between late 2018 and early 2020 was performed. The distribution of HPV genotypes in each Bethesda category was evaluated. A total of 13,160 smears were evaluated; 75.5% were from African American women. Of those tested for HR-HPV (10,060), 1412 (14%) were HR-HPV positive. In all diagnostic categories of the Bethesda classification system, non-16/18/45 HR-HPV genotypes were more prevalent, ranging from 60.8% even in high-grade squamous intraepithelial lesion to 90.4% in negative for intraepithelial lesion or malignancy. In this study with a predominantly African American population, non-16/18/45 HR-HPV genotypes were prevalent in the majority (60.8%) of high-grade squamous intraepithelial lesion cases. Ethnic variability should be considered when deciding which HPV genotypes to integrate into the HPV vaccine. • The distribution of human papillomavirus (HPV) genotypes in each Bethesda category of cervical Pap tests in our institution (Grady Memorial Hospital, Atlanta, GA) between late 2018 and early 2020 was analyzed. • A total of 13,160 Pap smears were evaluated and 75.5% were from African American women. • Overall, HPV 16/18/45 positivity accounted for 18% of all high-risk HPV–positive cases while non-16/18/45 high-risk HPV genotypes accounted for 82%. • Across each of the diagnostic categories of the Bethesda classification system, non-16/18/45 high-risk HPV genotypes were more prevalent, ranging from 60.8% even in high-grade squamous intraepithelial lesion to 90.4% in negative for intraepithelial lesion or malignancy, and this difference was significantly different in almost all the Bethesda categories. • Ethnic variability should be considered when deciding which HPV genotypes to integrate into the HPV vaccine. [ABSTRACT FROM AUTHOR]

Few studies have assessed the impact of the coronavirus disease 2019 (COVID-19) pandemic on immunization coverage for adolescents, and little is known about how coverage has changed throughout the pandemic. We aimed to: (1) assess the change in coverage for school-based vaccines in Alberta, Canada resulting from the pandemic; (2) determine whether coverage differed by geographic health zone and school type; and (3) ascertain whether coverage has returned to pre-pandemic levels. Using a retrospective cohort design, we used administrative health data to compare coverage for human papillomavirus (HPV) and meningococcal conjugate A, C, Y, W-135 (MenC-ACYW) vaccines between pre-pandemic (2017–2018 school year) and pandemic (2019–2020 and 2020–2021 school years) cohorts (N = 289,420). Coverage was also compared by health zone and authority type. The 2019–2020 cohort was followed over one year to assess catch-up. Compared to 2017–2018, immunization coverage for HPV was significantly lower in the 2019–2020 (absolute difference: 60.8%; 95% CI: 60.4–61.3%) and 2020–2021 cohorts (absolute difference: 59.9%; 95% CI: 59.4–60.3%). There was a smaller, significant decline in MenC-ACYW coverage comparing 2017–2018 to 2019–2020 (absolute difference: 6.1%; 95% CI: 5.6–6.5%) and 2020–2021 (absolute difference: 32.2%; 95% CI: 31.6–32.7%). Private schools had low coverage overall, while coverage fluctuated by zone. During follow-up of the 2019–2020 cohort, coverage for HPV and MenC-ACYW increased from 5.6% to 50.2%, and 80.7% to 83.0%, respectively. There was a substantial decrease in school-based immunization coverage during the COVID-19 pandemic, and coverage has not returned to pre-pandemic levels, suggesting further catch-up is needed. [ABSTRACT FROM AUTHOR]

• The licensed HPV prophylactic vaccines have demonstrated extraordinary immunogenicity and efficacy. • Standardized measurement and reporting of immunogenicity are now extremely critical as HPV serology measurements are being proposed as endpoints in vaccine trials evaluating single-dose immunogenicity and efficacy and immunobridging studies. • Continued collective efforts to standardize and harmonize assays and reagents, implement a uniform reporting system, and coordinate research efforts will inform public health decisions and help accelerate reductions the HPV burden globally. The HPV Serology Laboratory in the Frederick National Laboratory for Cancer Research is working in partnership with the scientific community with the goal of standardizing and harmonizing current HPV serology assay platforms in response to the increasing number of immunobridging trials relying on serology data for approval of new vaccine dosing schedules and new formulations. A virtual meeting was held on June 29–30, 2021, to review the progress of the standardization initiative thus far and to bridge scientific gaps and outstanding questions. The main aims and outcomes of the meeting were to discuss: 1) standardization of assays and reagents; 2) International Standard calibration procedures; 3) assay cut-off values; 4) current immunobridging clinical trials; and 5) gaps and challenges in standardization of HPV serology. [ABSTRACT FROM AUTHOR]

Les patients atteints d'un cancer de l'oropharynx pris en charge par radiothérapie ou chimioradiothérapie sont à haut risque nutritionnel. L'objectif de l'étude était de définir l'évolution de leur état nutritionnel en fonction de leur statut HPV (papillomavirus humains). Il s'agit d'une étude rétrospective monocentrique (août 2017–décembre 2020) incluant 48 patients atteints d'un carcinome épidermoïde de l'oropharynx pris en charge par chimioradiothérapie (14 induits par les HPV et 34 non-induits). Le risque nutritionnel au moment du bilan tumoral a été évalué par la perte de poids, la capacité à avaler et la présence de troubles digestifs en quatre stades de gravité croissants. Le statut nutritionnel a été évalué par le poids et le nutrition risk index (NRI) lors du bilan tumoral, avant le début et à 3 mois de la fin de la chimioradiothérapie. Au cours de la chimioradiothérapie, le NRI et le score « systemic inflammatory response index » (SIRI = neutrophiles * monocytes/lymphocytes) ont été évalués chaque semaine. Les patients atteints d'un cancer de l'oropharynx induit par les HPV étaient moins à risque nutritionnel lors du bilan tumoral (50 % de grade ≥ 2 contre 85 %, p = 0,02), perdaient plus de poids (6 % de leur poids contre 3 %, p = 0,05), et augmentait leur SIRI de 7,5 points de plus que les patients atteints d'un cancer de l'oropharynx non-induit par les HPV (p = 0,04) au cours de la chimioradiothérapie. Les patients atteints d'un cancer de l'oropharynx induit par les HPV sont à haut risque nutritionnel même en absence de dénutrition à la prise en charge. Patients with oropharyngeal cancer are at high nutritional risk before and during treatment. Little is known about the influence of human papillomavirus (HPV) infection on nutritional status and its evolution during treatment. A single-center retrospective study was conducted between August 2017 and December 2020 including 48 patients (14 HPV-induced: HPV+ and 34 non-HPV-induced: HPV−) with oropharyngeal squamous cell carcinoma treated by radiotherapy ± chemotherapy (RT/CT). Nutritional risk at the time of tumor assessment (TA) was assessed by weight loss, swallowing ability, and the presence of digestive disorders in 4 stages of increasing severity. Nutritional status was assessed by weight and nutrition risk index (NRI) at the time of TA, before the start and at 3 months from the end of RT ± CT. During RT ± CT, the NRI and the systemic inflammatory response index (SIRI = neutrophils * monocytes/lymphocytes) were assessed weekly. HPV + patients were at lower nutritional risk at TA (50% grade ≥ 2 vs 85%, P = 0.02), lost more weight (6% of their body weight vs 3%, P = 0.05), and increased their SIRI by 7.5 points more than HPV− patients (P = 0.04) during RT/CT. HPV+ oropharyngeal cancer patients are at high nutritional risk even in the absence of undernutrition at the outset of management. [ABSTRACT FROM AUTHOR]

• We formulate a two-sex epidemic model that incorporates the most important epidemiological features of HPV infection. • We use the optimal control theory to determine the best deployment strategy for HPV vaccine distribution. • Vaccination of 12-year-old girls alone cannot lead to the eradication of HPV-associated cancers. • The order of vaccination priority should be young girls, adult females, young boys, and finally adult males. • Allocating as much vaccines as possible early and then gradually decrease vaccination rates is the optimal deployment. Human papillomavirus (HPV) vaccines have been introduced in several countries and have shown positive results in reducing HPV infection and related diseases. Nevertheless, immunization programs remain sub-optimal and more effort is needed to design efficient vaccination deployment. We formulate a two-sex deterministic mathematical model that incorporates the most important epidemiological features of HPV infection and associated cancers. To assess the population-level impact of HPV immunization programs, the model incorporates school-based vaccine delivery for juveniles and catch-up vaccination for adults. The dynamics of the model are rigorously analyzed using the next-generation operator, the center manifold theorem, and normal forms theory. We formulate an optimal control problem to determine the best deployment strategy for HPV vaccination for several plausible scenarios. We establish the existence of solutions of the optimal control problem, and use Pontryagin's Maximum Principle to characterize the necessary conditions for optimal control solutions. The findings suggest that if girls-only programs are complemented with catch-up vaccination for adult females, such program has the potential to achieve HPV-associated cancers eradication even if boys and males do not receive the vaccine. We also find that the optimal vaccine deployment, in terms of minimizing HPV associated diseases and the cost of vaccination, is to allocate as much vaccines as possible at the initial phase of the epidemic and once a high vaccination coverage is reached then gradually decrease vaccination rates. [ABSTRACT FROM AUTHOR]

Viruses are the most abundant and genetically diverse entities on the planet, infect all life forms and have evolved with their hosts. To date, 263 viral species have been identified that infect humans, of which only seven are considered type I oncogenic. Human papillomavirus (HPV) is the main virus associated with cancer and is responsible for practically all cases of cervical carcinoma. Screening tests for early detection have been available since the 1960s. Undoubtedly, the entailment between knowledge of HPV biology and the natural history of cervical cancer has contributed to the significant advances that have been made for its prevention since the 21st century, with the development of prophylactic vaccines and improved screening strategies. Therefore, it is possible to eradicate invasive cervical cancer as a worldwide public health problem, as proposed by the WHO with the 90–70–90 initiative based on vaccination coverage, screening, and treatment, respectively. In addition, the emerging knowledge of viral biology generates opportunities that will contribute to strengthening prevention and treatment strategies in HPV-associated neoplasms. [ABSTRACT FROM AUTHOR]

Replacing cisplatin with cetuximab concurrently during radiotherapy has been one of the strategies of treatment de-escalation in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). However, until recently, there were limited data on the efficacy and safety of such an approach. A systematic search of the literature was carried out to identify prospective randomised controlled trials comparing definitive cisplatin-based chemoradiotherapy (CT-RT) versus cetuximab-based bioradiotherapy (BRT) in HPV-positive OPSCC. Overall survival and locoregional control were primary outcomes of interest; rates of acute and late toxicities (≥grade 3) were secondary end points. Outcome data were aggregated using a random-effects model as per Cochrane methodology including risk of bias assessment and expressed as hazard ratio or risk ratio as appropriate with respective 95% confidence intervals. Data from five randomised controlled trials involving 1560 patients with HPV-positive OPSCC were aggregated in the meta-analysis. Cetuximab-based BRT was associated with a significantly increased risk of death (hazard ratio = 2.83, 95% confidence interval 1.22–6.57; P = 0.02) and locoregional relapse (hazard ratio = 2.78, 95% confidence interval 1.77–4.39; P < 0.0001) compared with cisplatin-based CT-RT. Cisplatin was associated with higher rates of acute ≥grade 3 toxicity in terms of acute kidney injury, dry mouth, febrile neutropenia, hearing impairment, nausea and vomiting, whereas dermatitis and acneiform rash were more common with cetuximab. There were no significant differences in overall rates of late ≥grade 3 toxicity (risk ratio = 0.63, 95% confidence interval = 0.36–1.10; P = 0.10). In conclusion, there is moderate-certainty evidence that cetuximab-based BRT leads to inferior efficacy outcomes compared with cisplatin-based CT-RT in the definitive curative-intent management of HPV-associated OPSCC. [ABSTRACT FROM AUTHOR]

Some public health professionals have expressed concern that the COVID-19 pandemic has increased vaccine hesitancy about routine childhood vaccines; however, the differential prevalence of vaccine hesitancy about specific vaccines has not been measured. Data from the National Immunization Survey-Child COVID-19 Module (NIS-CCM) were analyzed to assess the proportion of children ages 6 months–17 years who have a parent with hesitancy about: COVID-19, influenza, human papillomavirus (HPV) (for children ≥ 9 years) vaccines, and "all other childhood shots." Interviews from October 2022 through April 2023 were analyzed. The percentage of children with a vaccine-hesitant parent varied by vaccine. 55.9% of children had a parent hesitant about COVID-19 vaccine, 30.9% hesitant about influenza vaccine, 30.1% hesitant about HPV vaccine, and 12.2% had a parent hesitant about other vaccines such as measles, polio, and tetanus. The study findings suggest that differential interventions and communications to parents be used to educate about COVID-19, influenza, HPV, and routine childhood vaccinations because the hesitancy levels differ widely. [ABSTRACT FROM AUTHOR]

• Effective HPV therapeutic vaccines could reduce HPV-related cancer and associated deaths. • An expert convening was held in September 2023 to provide guidance on vaccine trial design. • Study design for vaccines targeting cervical precancers has regulatory precedent. • Licensure pathways for treating existing HPV infection is less clear. • Early engagement with regulators with supportive data is strongly encouraged. Cervical cancer is a major cause of morbidity and mortality globally with a disproportionate impact on women in low- and middle-income countries. In 2021, the World Health Organization (WHO) called for increased vaccination, screening, and treatment to eliminate cervical cancer. However, even with widespread rollout of human papillomavirus (HPV) prophylactic vaccines, millions of women who previously acquired HPV infections will remain at risk for progression to cancer for decades to come. The development and licensing of an affordable, accessible therapeutic HPV vaccine, designed to clear or control carcinogenic HPV and/or to induce regression precancer could significantly contribute to the elimination efforts, particularly benefiting those who missed out on the prophylactic vaccine. One barrier to development of such vaccines is clarity around the regulatory pathway for licensure. In Washington, D.C. on September 12–13, 2023, a meeting was convened to provide input and guidance on trial design with associated ethical and regulatory considerations. This report summarizes the discussion and conclusions from the meeting. Expert presentation topics included the current state of research, potential regulatory challenges, WHO preferred product characteristics, modeling results of impact of vaccine implementation, epidemiology and natural history of HPV infection, immune responses related to viral clearance and/or precancer regression including potential biomarkers, and ethical considerations. Panel discussions were held to explore specific trial design recommendations to support the licensure process for two vaccine indications: (1) treatment of prevalent HPV infection or (2) treatment of cervical precancers. Discussion covered inclusion/exclusion criteria, study endpoints, sample size and power, safety, study length, and additional data needed, which are reported here. Further research of HPV natural history is needed to address identified gaps in regulatory guidance, especially for therapeutic vaccines intended to treat existing HPV infections. [ABSTRACT FROM AUTHOR]

Human Papillomavirus (HPV) is a widespread infection associated with various cancers, including cervical, oropharyngeal, anal, and genital cancers. This infection contributes to 5 % of global cancer cases annually, affecting approximately 625,600 women and 69,400 men. Cervical cancer remains the most prevalent HPV-linked cancer among females, with the highest incidence seen in low and middle-income countries (LMICs). While most HPV infections are transient, factors such as HPV variants, age, gender, and socioeconomic status influence transmission risks. HPV is categorized into high-risk (HR-HPV) and low-risk types, with strains like HPV 16 and 18 displaying distinct demographic patterns. The intricate pathogenesis of HPV involves genetic and epigenetic interactions, with HPV oncogenes (E6 and E7) and integration into host DNA playing a pivotal role in driving malignancies. Early diagnostics, utilizing HPV DNA testing with surrogate markers such as p16, and advanced molecular techniques like PCR, liquid biopsy, and NGS, significantly impact the management of HPV-induced cancers. Effectively managing HPV-related cancers demands a multidisciplinary approach, including immunotherapy, integrating current therapies, ongoing trials, and evolving treatments. Prevention via HPV vaccination and the inclusion of cervical cancer screening in national immunization programs by conventional Pap smear examination and HPV DNA testing remains fundamental.Despite the preventability of HPV-related cancers, uncertainties persist in testing, vaccination, and treatment. This review article covers epidemiology, pathogenesis, diagnostics, management, prevention strategies, challenges, and future directions. Addressing issues like vaccine hesitancy, healthcare disparities, and advancing therapies requires collaboration among researchers, healthcare providers, policymakers, and the public. Advancements in understanding the disease's molecular basis and clinical progression are crucial for early detection, proper management, and improved outcomes. • HPV causes around 5% of malignancies, with cervical cancer being the most common cancer among LMICs women. • HPV's complex pathogenesis involves genetic and epigenetic factors and the role of oncogenes. • Diagnosis includes molecular methods of HPV DNA diagnosis like PCR, Liquid biopsy and P16 IHC. • Multidisciplinary approaches, personalized care, vaccination, and cervical screening are crucial. • Collaborative efforts for improved outcomes and addressing challenges like vaccine hesitancy are needed. [ABSTRACT FROM AUTHOR]

• The potential of de-escalation to improve quality of life while maintaining high cure rates for human papillomavirus (HPV)-positive oropharyngeal cancer is being realized. • Significant variability exists in the design of clinical trials studying de-escalation, and uncertainty persists in how to apply the evidence to practice. • Progress in refining selection criteria and in monitoring response will lead to further individualization of de-escalation strategies in the future. The emergence of treatment de-escalation as a feasible option for patients with newly diagnosed human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma has generated considerable excitement among both providers and patients alike. Since HPV-positive oropharyngeal carcinoma has been shown to be a unique entity with distinct clinical and molecular characteristics, the rationale for customizing treatment for patients with this disease is compelling. Indeed, evidence has accumulated demonstrating that patients with HPV-positive oropharyngeal cancer have a significantly improved prognosis as a result of their exquisite radiosensitivity compared to their HPV-negative counterparts and thus might possibly be targeted with de-escalated approaches. The fundamental goal of de-escalation is to maintain the high cure and survival rates associated with traditional approaches while reducing the intensity of treatment and thus the incidence of both short- and long-term toxicity. Given the rapidly increasing incidence of this disease, particularly among younger patients who are generally healthy, the focus on quality of life seems germane. Although the exact reason for the improved sensitivity of HPV-positive oropharyngeal carcinoma to treatment is uncertain, prospective studies have now been published demonstrating that de-escalated radiation can successfully maintain the high rates of cure and preserve quality of life for appropriately selected patients with this disease. However, these studies have been fairly heterogeneous in design, and it remains questionable how to apply their findings to real-world practice. The potential of integrating translational approaches into clinical paradigms is also just starting to become recognized. Consequently, multiple uncertainties continue to exist with respect to de-escalation for HPV-positive oropharyngeal cancer, and these questions comprise the crux of this review. [ABSTRACT FROM AUTHOR]

Introduction: School-based immunization programs offer an accessible route to routine vaccines for students. During the COVID-19 pandemic, school closures to comply with public health measures had a drastic effect on school-based immunization program delivery and associated vaccine uptake. We sought to integrate findings from a mixed methods study to co-develop evidence-based and theory-informed recommendations with a diverse group of stakeholders (i.e., decision makers, healthcare providers, school staff, parents and adolescent students) to address barriers to new and existing school-based immunization programs. Methods: Findings from a mixed methods study were integrated using a joint display and narrative summary. These findings were mapped through the Behaviour Change Wheel, a series of tools designed to facilitate the development of behaviour change interventions. Draft recommendations were provided to previous mixed methods study participants who consented to participating in future phases of the research study (n = 26). Feedback was captured using a Likert-scale survey of acceptability, practicality, effectiveness, affordability, safety and equity (APEASE) criteria, with feedback and additional insights captured using open-ended textboxes. Data was used to revise and finalize recommendations. Results: Applying the Behaviour Change Wheel, we drafted 26 evidence-based, theory-informed recommendations to address barriers to school-based immunization programs. Participants (n = 16) provided feedback, with half of the recommendations scoring 80% or higher across all six APEASE criteria. The remaining 13 recommendations received a moderate score across one or more criteria. Stakeholders identified a high level of interest in expanding the use of e-consent forms, expanding programming to offer a meningitis B vaccine, and recommendations to ease student anxiety. Conclusion: We co-developed a range of recommendations to improve school-based immunization programs with stakeholders using data generated from a mixed methods study. Implementation of any single or combination of recommendations will need to be tailored to local clinic procedures, school system and health system resources. [ABSTRACT FROM AUTHOR]

[Display omitted] The current study sought to determine if the release of COVID-19 vaccines influenced Alabama mothers' attitudes and behaviors regarding HPV vaccination of their adolescent children. A social media survey was conducted August − September 2022 among mothers of adolescents ages 9–18, who self-identified as Alabama residents and their child(ren)'s primary medical decision maker. The survey assessed demographics, vaccine knowledge and opinions, vaccination history, influences on vaccination decisions, and how COVID-19 vaccine release affected vaccine opinions. Univariable and multivariable analyses were conducted. Of 241 responses, most participants were white (82.0 %, n = 196), non-Hispanic (96.6 %, n = 230), and privately insured (64.5 %, n = 151), with annual household incomes ≥$61,000 (45.4 %, n = 103). The majority (60.8 %) reported that their child either had or planned to receive the HPV vaccine. The release of COVID-19 vaccines did not change the majority of parental opinions towards HPV, with 78.5 % (n = 161) reporting no change. Among those who experienced a change, 25 % (n = 5) reported an increased likelihood of having their child vaccinated for HPV and 75 % (n = 15) reported a decrease in likelihood. Moderate and high HPV knowledge scores were associated in multivariable analysis with increased likelihood of having their child vaccinated for HPV ("moderate" knowledge AOR: 12.4, 95 % CI: 1.98–78.1; "high" knowledge AOR: 12.8, 95 % CI: 2.00–82.1). Positive HPV opinion scores in the univariable analysis similarly showed increased odds (AOR = 1.5). These findings indicate that, in this population, COVID-19 vaccine release did not significantly impact subsequent HPV vaccination decision making. Parental perceptions regarding vaccination are critical to informing future interventions. [ABSTRACT FROM AUTHOR]

• Research on nationally implemented HPV vaccination programmes for gbMSM is limited. • A range of socio-demographic factors predicted HPV vaccination in gbMSM. • Health-care provider recommendation was a very strong predictor of vaccination. • A norm-based intervention for gbMSM did not affect HPV vaccination intentions. This study tested social cognitive predictors of vaccination and a dynamic norms intervention for increasing HPV vaccination intentions in gay, bisexual, and other men who have sex with men (gbMSM). The study employed an experiment embedded in a cross-sectional survey. Participants (N = 217; gbMSM aged 18–45 in Ireland) provided cross-sectional data on sociodemographic constructs and constructs from the Theory of Planned Behaviour and the Health Belief Model. Unvaccinated participants (n = 94) were randomised to one of three experimental conditions (no norms, static norms, dynamic norms) and presented with information on HPV vaccine uptake in gbMSM in Ireland before reporting vaccination intentions. In an adjusted logistic regression, significant predictors of vaccination included being in a relationship (OR = 8.69 [1.09, 38.91]), perceived susceptibility (OR = 1.11 [1.04, 1.19]), healthcare provider recommendation (OR = 107.24 [26.87, 427.99]), and perceived barriers (OR = 0.83 [.7, 0.98]). Adjusted linear regression models showed no significant differences in HPV vaccination intentions between no norms and static norms (B = −1.24 [−4.6, 2.12]), dynamic norms and static norms (B = −0.62 [−3.86, 2.63]), and dynamic norms and no norms (B = 0.62 [−2.74, 3.98]). Connectedness to the LGBT+ community did not moderate these differences. The need for greater awareness of susceptibility, the impact of barriers, and the strong influence of a recommendation from a healthcare provider in predicting HPV vaccination among gbMSM are critical considerations for policymakers. Dynamic norm messaging may be less effective for vaccination than other behaviours more easily influenced by social norms. Efforts to implement dynamic norm-based interventions in gbMSM should consider the limited evidence of efficacy. [ABSTRACT FROM AUTHOR]

The article "Characterization of oral microbiota in HPV and non-HPV head and neck squamous cell carcinoma and its association with patient outcomes" by Chan et al. investigates the relationship between oral microbiota, HPV infection, and patient outcomes in head and neck squamous cell carcinoma (HNSCC). This comprehensive study, involving 166 Chinese adults, utilized advanced sequencing techniques to profile bacterial and HPV regions in paired tumor and control tissues. The findings highlight the complex interplay between microbiota dysbiosis, HPV infection, and HNSCC progression. Despite the robustness of the study, limitations include potential biases in DNA extraction and PCR amplification, and unaccounted environmental factors. Recommendations for future research include increasing sequencing depth, comparing DNA extraction methods, using multiple bioinformatics pipelines, and controlling for environmental variables. Longitudinal studies and microbiota-targeted interventions are suggested to further elucidate the role of oral microbiota in HNSCC and improve patient outcomes. [ABSTRACT FROM AUTHOR]

• ALA-PDT significantly inhibited the viability while promoted apoptosis of human cervical cancer SiHa cells. • ALA-PDT remarkably suppressed SiHa cell migration, invasion and epithelial-mesenchymal transition (EMT). • The anti-tumor activities of ALA-PDT on SiHa cells appeared to be via suppressing miR-152–3p and thereby activiating JAK1/STAT1 pathway in vitro and vivo. • The study elucidated the underlying molecular mechanism of ALA-PDT on cervical cancer SiHa cells. Cervical cancer ranks the fourth most prevalent type of cancer worldwide, characterized by a notably low survival rate, particularly in its metastatic stage. Despite 5-aminolevulinic acid photodynamic therapy (ALA-PDT) demonstrating potential anti-tumor effects against cervical cancer, the intricate mechanisms underlying its efficacy necessitate further investigation. Here, the study aims to elucidate the impact of ALA-PDT on the cancer cell viability, invasion and migration, alongside delineating the underlying molecular mechanisms. Cervical cancer SiHa cells were subjected to ALA and red light irradiation, and we then measured the ALA-PDT's effects on cell functions using various assays. The potential interaction between miR-152–3p and JAK1 was explored through bioinformatics analyses and validated by dual-luciferase reporter assays. Post-transfection with miR-152–3p and JAK1 vectors, cellular functions were re-evaluated. The efficacy of ALA-PDT in tumor suppression was further investigated through tumor transplantation experiment in vivo. ALA-PDT markedly suppressed SiHa cell viability, invasion and migration, impacting critical markers of proliferation, apoptosis, and epithelial-mesenchymal transition(EMT). And these effects were echoed by the inhibition of miR-152–3p. JAK1 was identified as a direct target of miR-152–3p, and ALA-PDT was found to regulate the expression levels of miR-152–3p, consequently influencing the JAK1/STAT1 signaling pathway. Augmentation of miR-152–3p expression and inhibition of the JAK1/STAT1 pathway mitigated the anti-cancer effects of ALA-PDT, whereas JAK1 overexpression diminished these effects. In vivo analyses demonstrated that ALA-PDT suppressed tumor growth and modulated the miR-152–3p/JAK1/STAT1 pathway expression. ALA-PDT inhibits the viability, invasion, and migration of cervical cancer SiHa cells by modulating the miR-152–3p/JAK1/STAT1 axis, offering a promising therapeutic avenue for combating invasive cervical cancer. [ABSTRACT FROM AUTHOR]

• Papilloma DNA virus which is most common sexually transmitted disease to both sexes. • There is a requirement within the existing curriculum and syllabus to include more education, seminars, and training courses on HPV. • Application of a virtual classroom viral module or communicating workshop would likely improve knowledge Papilloma DNA virus which is most common sexually transmitted disease to both sexes. The infection either benign or malignant affecting head and neck region. Assess the level of knowledge, and attitude, of medical students about Human Papilloma virus, vaccine, and its role in head and neck cancer development. A descriptive cross-sectional survey was conducted on 357 undergraduate medical students. Data were collected by online Google form researcher made questionnaires which was analyzed using SPSS 25. There are 357 medical undergraduate students from different educational stages participated in this study. This study was shown 176 (49.3 %) of medical students agreed that smoking Tobacco are the most common causes for development oral cancer followed by viruses 98 (27.5 %), that 57.4 % of medical students reported that HPV was the main viral cause. As for the questions concerning HPV mode of transmission, almost (85.7 %) stated sexual transmission, (79.8 %) skin to skin direct contact. Most of the participants (92.2 %) agreed that primary prevention can decrease the risk of infection with HPV, and 43.4 % strongly agreed that vaccination plays an important role in HPV prevention. There is a requirement within the existing curriculum and syllabus to include more education, seminars, and training courses on HPV, role in HNC, prevention, and vaccination, and mainly for students in the preclinical academic years. Application of a virtual classroom viral module or communicating workshop would likely improve knowledge and attitudes of the students for their future medical tasks. [ABSTRACT FROM AUTHOR]

• Patient distress and anxiety significantly improved following circulating tumor DNA (ctDNA) surveillance testing for HPV (+) oropharyngeal squamous cell carcinoma (OPC). • Overall, 95.5% of patients responded ctDNA surveillance testing was beneficial, while 100% felt "somewhat" or "extremely" confident in ctDNA as a monitoring tool. • While 58.1% of patients would be willing to pay out of pocket for ctDNA surveillance, only 25.6% would be willing to continue the test indefinitely. Circulating tumor DNA assays have robust potential as molecular surveillance tools. They may also exacerbate patient distress without improving outcomes. We investigate patient acceptability of a validated ctHPVDNA assay (NavDx) during cancer surveillance for HPV(+) oropharyngeal cancer (OPC). Consented HPV(+) OPC participants completed the NCCN Distress Thermometer, the Hospital Anxiety Depression Scale (HADS), and the Functional Assessment of Cancer Therapy-General (FACT-G) scale both (1) before NavDx blood draw, and (2) after results were provided. Patients then completed a series of focused questions related to their perceptions of the assay. Overall, 55 patients completed the study, with 98.2 % showing no recurrence. For the NCCN Distress Thermometer, median patient distress decreased (2.0 (IQR 1–5) vs. 1.0 (IQR 0–3)) (p < 0.001) in association with NavDx. Using scores ≥ 4 as a cutoff point to define clinically elevated distress, scores also improved (36.4 % vs. 18.2 %, p = 0.031). For HADS, anxiety significantly improved (5.0 (IQR 2.0–7.0) vs. 3.0 (IQR 1.0–6.5)) (p = 0.037), but not depression (3.0 (IQR 1.0–7.0) vs. 3.0 (IQR 1.0–6.5)) (p = 0.870). FACT-G scores showed no substantial differences. On survey questionnaires, 95.5 % of patients believed the test to be helpful, and 100 % felt "somewhat" or "extremely" confident in the assay as a monitoring tool. While 59.1 % felt that it reduced anxiety, 88.4 % concordantly felt that it did not introduce anxiety. ctHPVDNA as a molecular surveillance tool reduced distress levels in HPV(+) OPC patients, with notably high patient confidence in the approach. Further investigation is warranted to judiciously incorporate this emerging modality in surveillance guidelines. [ABSTRACT FROM AUTHOR]

High-risk human papillomavirus (hrHPV) is an emerging risk factor for sinonasal squamous cell carcinoma (SNSCC). The goal of this study was to assess the prevalence of hrHPV and subtype distribution in SNSCC and correlation with patient and clinical characteristics. This retrospective cohort study included 43 cases diagnosed with incident primary SNSCC at the University of Cincinnati Medical Center from 2010 to 2015. The prevalence of hrHPV was interrogated using a multi-assay approach that included p16 immunohistochemistry (IHC), RNA in-situ hybridization (ISH), and hrHPV DNA sequencing. The association of hrHPV with 5-year overall survival (OS) and 2-year disease-free survival (DFS) was assessed. Fourteen cases (32.6 %) were classified as hrHPV positive, based on the a priori definition of having either a positive RNAScope™ ISH test or hrHPV DNA and p16-positive IHC; 9 cases (20.9 %) were positive for all three tests. All cases that arose from an inverted sinonasal papilloma (ex-ISP) were negative for hrHPV. HPV16 was the most common subtype among hrHPV positive cases (58.8 %), followed by HPV18 (17.6 %). No significant association was observed between hrHPV and OS or DFS after adjusting for potential confounding. hrHPV is prevalent in a sizable fraction of SNSCC. Additional studies are needed to better elucidate the relationship with patient survival outcomes and determine the optimal testing modality for prognostication. [ABSTRACT FROM AUTHOR]

Recent studies demonstrated that human papillomavirus (HPV) specific immunoglobulins (IgG) are present and detectable in non-invasively collected first-void urine (FVU) samples. As IgG levels in urine are low, we evaluated the potential of a highly sensitive HPV16-specific assay based on time-resolved fluorescence, DELFIA, and compared it with three immunoassays, GST-L1-MIA, M4ELISA, and M9ELISA. A total of 225 paired serum and FVU samples from two cohorts of healthy female volunteers were analyzed. Strong Spearman rank correlations between HPV16-specific IgG results measured with DELFIA, M4ELISA, GST-L1-MIA, and M9ELISA were found for both sample types (r s > 0.80). Additionally, total human IgG results, determined in all samples using HTRF human IgG kit and BioPlex Pro™ Human Isotyping Assay, were compared. Moderate correlations between total human IgG concentrations in FVU samples were found for the two total IgG assays (r s ≥ 0.42, p < 0.0001), while correlations for serum were non-significant. In conclusion, the HPV16-DELFIA assay is usable for detecting HPV16-specific antibodies in FVU and serum samples. As total human IgG remains an interesting parameter for the normalization of HPV-specific IgG in FVU, the accuracy of both assays needs to be validated further. • HPV16 DELFIA assay is a suitable immunoassay for the detection of HPV16 antibodies. • HPV16-specific DELFIA has high sensitivity in first-void urine and serum samples. • DELFIA sensitivity is similar to existing VLP-based immunoassays M4- and M9ELISA. • Normalization of antibody concentration with total IgG did not have an added value. [ABSTRACT FROM AUTHOR]

The human papillomavirus (HPV) is the most common diagnosed sexually transmitted infection in the world. The most frequent disease linked to HPV is cervical cancer as well as other cancers including those of the vulva, vagina, penis, anus, and oropharynx. Our research sought to evaluate the knowledge and attitudes concerning human papillomaviruses and their vaccine among students enrolled in Altınbaş University's faculties of health sciences. A cross-sectional study was carried out using a survey containing 41 questions about demographic variables, knowledge, and attitudes toward HPV and HPV vaccines. The questions were distributed to students via Google form using social media applications such as WhatsApp. The study involved 144 students, 71.5 % of whom were female. 37.5 % of the participants learned about HPV from social media. Knowledge of HPV is present in 82 % of females and 25 % of males. Most of the questions had more accurate replies from female than from male students p < 0.05. As a result, 88 %, 46 % of female respondents and 27 %, 14 % of male respondents, respectively, correctly answered the questions about who should receive HPV vaccinations p < 0.001 and how many doses are necessary. Participants' awareness of HPV, HPV vaccination, and cervical cancer was rather high when compared to other research. However, there are knowledge gaps that need to be corrected and provided through educational programs. [ABSTRACT FROM AUTHOR]