Evaluation of Some Prognostic Biomarkers in Human Papillomavirus-Related Multiphenotypic Sinonasal Carcinoma.

Background: Human papillomavirus (HPV)-related multi phenotypic sinonasal carcinoma (HMSC) is a recently described tumor subtype with an unknown prognosis, often misdiagnosed with other sinonasal carcinomas, and associated with high-risk HPV (HR-HPV). The present study aimed to evaluate the expression of vascular endothelial growth factor (VEGF), Bcl-2-associated X protein (BAX), epidermal growth factor receptors (EGFR), ProExTMC, and human telomerase reverse transcriptase (hTERT) and assess their association with survival and clinicopathological characteristics. Methods: Between 2017 and 2022, 40 HMSC patients underwent surgical resection at the School of Medicine, Zagazig University Hospitals (Zagazig, Egypt). Tissue samples were examined for the presence of HR-HPV; absence of myeloblastosis (MYB), MYB proto-oncogene like 1 (MYBL1), and nuclear factor I/B (NFIB) fusions and the presence of myoepithelial proteins (calponin, S100, SMA), squamous differentiation markers (p63, p40, calponin), VEGF, BAX, ProExTMC, and hTERT by immunohistochemistry. All patients were followed up for about 54 months until death or the last known survival data. Data were analyzed using the Chi square test and Kaplan-Meier method. Results: The expression of VEGF, hTERT, and ProExTMC was significantly associated with age, advanced tumor stages, lymph node metastasis, tumor size, mortality, relapse, poor disease-free survival (DFS), and overall survival (OS) (P<0.001). BAX expression was significantly associated with tumor size, age, poor DFS, and relapse (P=0.01, P<0.001, P=0.035, and P=0.002, respectively). Conclusion: HMSC is strongly associated with HR-HPV. The expression of VEGF, EGFR, BAX, hTERT, and ProExTMC is associated with aggressive malignant behavior, poor survival, and poor prognosis, making them novel prognostic biomarkers for targeted therapeutics in HMSC.

Mapping the research landscape of HPV-positive oropharyngeal cancer: a bibliometric analysis.

OBJECTIVE: The aim of the study is to evaluate the scientific interest, the collaboration patterns and the emerging trends regarding HPV+ OPSCC diagnosis and treatment. MATERIALS AND METHODS: A cross-sectional bibliometric analysis of articles reporting on HPV+ OPSCC within Scopus database was performed and all documents published up to December 31th, 2022 were eligible for analysis. Outcomes included the exploration of key characteristics (number of manuscripts published per year, growth rate, top productive countries, most highly cited papers, and the most well-represented journals), collaboration parameters (international collaboration ratio and networks, co-occurrence networks), keywords analysis (trend topics, factorial analysis). RESULTS: A total of 5200 documents were found, published from March, 1987 to December, 2022. The number of publications increased annually with an average growth rate of 19.94%, reaching a peak of 680 documents published in 2021. The 10 most cited documents (range 1105-4645) were published from 2000 to 2012. The keywords factorial analysis revealed two main clusters: one on epidemiology, diagnosis, prevention and association with other HPV tumors; the other one about the therapeutic options. According to the frequency of keywords, new items are emerging in the last three years regarding the application of Artifical Intelligence (machine learning and radiomics) and the diagnostic biomarkers (circulating tumor DNA). CONCLUSIONS: This bibliometric analysis highlights the importance of research efforts in prevention, diagnostics, and treatment strategies for this disease. Given the urgency of optimizing treatment and improving clinical outcomes, further clinical trials are needed to bridge unaddressed gaps in the management of HPV+ OPSCC patients.

Prevalence of high-risk human papillomavirus infection and cervical lesions among female migrant head porters (kayayei) in Accra, Ghana: a pilot cross-sectional study.

BACKGROUND: Little attention has been given to the risk of high-risk human papillomavirus (hr-HPV) infection and cervical precancerous lesions among female migrant head porters (kayayei) in Ghana, as a vulnerable group, and to promote cervical screening in these women. This pilot study aimed to determine the prevalence of hr-HPV infection and cervical lesions among kayayei in Accra, the capital of the Greater Accra Region of Ghana and to describe our approach to triaging and treating these women. METHODS: This descriptive cross-sectional cohort study involved the screening of 63 kayayei aged ≥ 18 years at the Tema Station and Agbogbloshie markets in March 2022 and May 2022. Concurrent hr-HPV DNA testing (with the MA-6000 platform) and visual inspection with acetic acid (VIA) was performed. We present prevalence estimates for hr-HPV DNA positivity and VIA 'positivity' as rates, together with their 95% confidence intervals (CIs). We performed univariate and multivariable nominal logistic regression to explore factors associated with hr-HPV infection. RESULTS: Gross vulvovaginal inspection revealed vulval warts in 3 (5.0%) and vaginal warts in 2 (3.3%) women. Overall, the rate of hr-HPV positivity was 33.3% (95% CI, 21.7-46.7), whereas the VIA 'positivity' rate was 8.3% (95% CI, 2.8-18.4). In the univariate logistic regression analysis, none of the sociodemographic and clinical variables assessed, including age, number of prior pregnancies, parity, past contraceptive use, or the presence of abnormal vaginal discharge showed statistically significant association with hr-HPV positivity. After controlling for age and past contraceptive use, only having fewer than two prior pregnancies (compared to having ≥ 2) was independently associated with reduced odds of hr-HPV infection (adjusted odds ratio, 0.11; 95% CI, 0.02-0.69). CONCLUSION: In this relatively young cohort with a high hr-HPV positivity rate of 33.3% and 8.3% of women showing cervical lesions on visual inspection, we posit that kayayei may have an increased risk of developing cervical cancer if their accessibility to cervical precancer screening services is not increased.

Effectiveness of provider communication training for increasing human papillomavirus vaccine initiation at a safety-net health system.

Background: Strong provider recommendation can increase uptake of human papillomavirus (HPV) vaccination. Therefore, we developed and implemented a provider education intervention on communication strategies for recommending HPV vaccination with clinic-level audit and feedback (HPV: Communicating about HPV to Adults and Teens [HPV CHAT]). We aimed to evaluate the effect of HPV CHAT on HPV vaccine uptake in seven family medicine and pediatric clinics in a large urban health system (USA). Methods: We used a quasi-experimental design, where the eligible population included people aged 9-26 years with at least one encounter in June 2020-February 2023 at one of the participating community health clinics. We used interrupted time-series analysis to assess changes in the prevalence of HPV vaccine uptake. We used segmented Poisson regression with a log link function to estimate prevalence ratios (PR) and 95% confidence limits (CL) for level (immediate) and slope (over time) changes with adjustment for seasonality using Fourier transformation. Results: Our study population comprised 60,328 observations in which the median age was 17 years (interquartile range: 13-21). A majority (58%) were female and 87% were racial/ethnic minorities. Overall, we observed no sizeable effect of the intervention on HPV vaccination uptake. Nonetheless, heterogeneity was observed by age group with modest increases in individuals aged 9-12 and 13-17 years. Conclusion: Our provider feedback intervention had minimal effect on increasing prevalence of HPV vaccination in seven family medicine and pediatric clinics. Novel strategies are needed to address provider barriers related to HPV vaccination.

Advancements in mRNA Vaccines: A Promising Approach for Combating Human Papillomavirus-Related Cancers.

The human papillomavirus (HPV) is a typical sexually transmitted disease that affects different epithelial cells and can cause a number of health problems. HPV is mainly spread through sexual contact and is extremely contagious, even in the absence of obvious symptoms. It is linked to a number of malignancies, such as oropharyngeal, cervical, anal, vulvar, vaginal, and cutaneous as well as anogenital and cutaneous warts. Different vaccines targeting various HPV virus strains have been produced to prevent HPV infections. Vaccines can help prevent HPV-related illnesses, but they cannot cure malignancies that have already been caused by HPV. But new developments in mRNA vaccines have shown potential in combating malignancies linked to HPV. mRNA vaccines stimulate the immune system to identify and attack particular proteins present in viruses or tumour cells. The efficacy of mRNA vaccines in preventing HPV-related malignancies has been shown in preliminary experiments in mice. Additionally, in clinical trials aimed at individuals with HPV-related head and neck malignancies, personalised mRNA vaccines in combination with immune checkpoint drugs have demonstrated encouraging results. Even though mRNA vaccines have drawbacks and restrictions such as immunogenicity and instability, further research and development in this area has a great deal of promise for developing effective therapies for HPV-related malignancies.

The intentions of French health university students to recommend and to receive the HPV vaccine are mainly influenced by vaccine knowledge, confidence in vaccines and personal HPV vaccination.

INTRODUCTION: Despite documented effectiveness in preventing several cancers, genital warts and safety of Human Papillomavirus (HPV) vaccine, immunization coverage among French adolescents remains far from the 80 % target. University health students (HS) in France may promote HPV vaccine through a national service (Service Sanitaire des Etudiants en Santé). We aimed to evaluate intentions to recommend the HPV vaccine to friends and relatives, to receive HPV vaccine, and to identify factors associated with these attitudes. METHODS: We conducted a cross-sectional survey in five French Universities from October 2019 to February 2020, using a self-administered online questionnaire. We used bivariable and multivariable logistic regression models to identify determinants of behavior around HPV vaccine: (i) individual intention for vaccination, and (ii) vaccine recommendation to friends and relatives. RESULTS: Among the 732 respondents (180 men, 552 women), 305 (41.7%) reported previous HPV vaccination (54.5 % among women), 504 (68.9%) would recommend the HPV vaccine to friends and relatives, 532 (72.7%) respondents would be vaccinated today if it was recommended for them. Intentions to recommend or to receive the HPV vaccine were less frequent in nursing students compared to medical and pharmacy students. After adjustment for demographical factors, HPV vaccine knowledge was associated with intention [aOR 1.30 (95%-confidence interval, 1.15-1.47)] and recommendation [1.26 (1.10-1.45)], respectively. Additionally, adjusting for knowledge about HPV infections, and confidence in vaccines in general was associated with vaccine intention [1.55, (1.30-1.84)] and recommendation [1.52 (1.24-1.86)]. HPV-vaccinated HS were more prone to recommend the HPV vaccine to friends and relatives [10.9 (6.6-17.9)]. CONCLUSION: A majority of HS would accept and/or recommend HPV vaccines. HS with greater knowledge about the HPV vaccine were more prone to recommend it. Strengthening knowledge about HPV and its vaccination is probably necessary before their Involvement in a HPV immunization program.

Barriers and facilitators to the HPV vaccine: a multicenter qualitative study of French general practitioners.

BACKGROUND: In France, human papillomavirus (HPV) vaccination coverage is low, with 30.7% of 17-year-old girls having received a complete HPV vaccination schedule in 2020. AIM: To determine the perspective and behaviors of general practitioners (GPs) regarding HPV vaccination with their patients and if a reluctance is observed. DESIGN AND SETTING: A qualitative study based on semi-directed individual interviews was conducted between December 2019 and December 2020. A representative sample of GPs with various profiles were included in 4 French regions. METHOD: A purposive sampling was used and interviews were continued until data saturation was reached. The analysis was based on the grounded theory. RESULTS: Twenty-six GPs aged 29-66 years were interviewed. The measures taken by the French health authorities (lowering the target age, reimbursing the vaccine, extending the target population to boys) were perceived as facilitators. The reported barriers were organizational, due to low attendance of adolescents, and relational, mainly due to parental vaccine hesitancy. Physicians had to deal with fears about the perceived risks and concerns about sexuality conveyed by HPV vaccination and linked to the socio-cultural characteristics of the families. Physicians developed strategies, including scientific knowledge mobilization, empowerment of families by promoting health through prevention, repetition of the vaccination proposals, personal experience and relationship. Different practices were identified according to three GP typologies: effective, convinced but unpersuasive, and reluctant physicians. CONCLUSION: Based on these results, specific interventions, including communication techniques, especially for hesitant or unpersuasive physicians, are needed to enable GPs to become more effective.

Feasibility, accuracy and acceptability of self-sampled human papillomavirus testing using careHPV in Cambodia: a cross-sectional study.

OBJECTIVE: Self-sampled human papillomavirus (HPV) testing is a potential option for cervical cancer screening, but research is scarce in Cambodia. We evaluated the feasibility, accuracy, and acceptability of self-sampled HPV testing using careHPV. METHODS: A cross-sectional study including women aged 20-49 years attending 2 national hospitals in the capital city was conducted. Women underwent both self-sampling and clinician-sampling of specimens, and were then asked to complete an acceptability questionnaire. The paired samples were analyzed for high-risk HPV by careHPV and genotyped by polymerase chain reaction (PCR). RESULTS: A total of 375 women were eligible for inclusion. Based on PCR, 78.9% were negative for HPV in both self and clinician-samples, 9.9% had a complete HPV type match, and 6.1% had all HPV types in clinician-samples also detected in self-samples. In 5.1%, one or more HPV types identified in the clinician-samples were missed in self-samples. When using careHPV, the overall agreement between the 2 sampling methods was 95.7% (95% confidence interval [CI]=95.8-95.6) with good concordance (κ=0.66, 95% CI=0.56-0.76). Nearly 90% of the women preferred clinician-sampling over self-sampling, citing greater comfort, ease, and speed. CONCLUSION: Self-sampled HPV testing using careHPV could be an option for cervical cancer screening in Cambodia; however, it requires periodic quality control of handling procedures. In addition, women's health education regarding the accuracy of self-sampled HPV testing and the importance of follow-up in cases of positive results is needed.

The efficacy of topical imiquimod in high-grade cervical intraepithelial neoplasia: A systematic review and meta-analysis.

OBJECTIVE: A major side effect of cervical excision for high-grade cervical intraepithelial neoplasia (CIN) is premature birth. A non-invasive treatment for reproductive age women is warranted. The aim of the present study was to determine the efficacy of topical imiquimod in the treatment of high-grade CIN, defined as a regression to ≤CIN 1, and to determine the clearance rate of high-risk human papillomavirus (hr-HPV), compared with surgical treatment and placebo. METHODS: Databases were searched for articles from their inception to February 2023.The study protocol number was INPLASY2022110046. Original studies reporting the efficacy of topical imiquimod in CIN 2, CIN 3 or persistent hr-HPV infections were included. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses checklist. RESULTS: Five studies were included (n = 463). Histological regression to ≤CIN 1 was 55% in imiquimod versus 29% in placebo, and 93% in surgical treatment. Imiquimod-treated women had a greater odds of histological regression to ≤CIN 1 than placebo (odds ratio [OR] 4.17, 95% confidence interval [CI] 2.03-8.54). In comparison to imiquimod, surgical treatment had an OR of 14.81(95% CI 6.59-33.27) for histological regression to ≤CIN 1. The hr-HPV clearance rate was 53.4% after imiquimod and 66% after surgical treatment (95% CI 0.62-23.77). CONCLUSIONS: The histological regression rate is highest for surgical treatment followed by imiquimod treatment and placebo.

Impact of COVID-19 pandemic and vaccine perceptions on HPV vaccine hesitancy.

OBJECTIVE: This study evaluated the impact of the COVID-19 pandemic and vaccine perceptions on Human Papillomavirus (HPV) vaccine hesitancy. Secondary endpoints included comparing COVID-19 and HPV vaccination trends regarding time, community of residence, and unmet social needs. METHODS: This was a survey-based, cross-sectional study that included 101 participants who were recruited through the Wyandotte County Public Health Department. Participants were eligible for inclusion in this study if they were a parent/guardian of one or more children aged 13 to 17; English- or Spanish-speaking. This study took place in Wyandotte County, Kansas. Descriptive statistics and chi-square analyses were utilized. RESULTS: There was no difference in completion of COVID-19 and HPV vaccines (p = 0.0975). Significantly more individuals started and did not finish the HPV vaccine series compared to the COVID-19 vaccine series (p = 0.0004). Most participants indicated their opinion on the HPV vaccine had not changed due to the pandemic (71.3 %). Participants who felt familiar with HPV had higher rates of HPV vaccine completion. While 77 % of participants felt extremely or moderately familiar with HPV, 61.4 % were unaware of its association with oropharyngeal cancer. CONCLUSION: There was minimal change in parents' perception of the HPV vaccine due to the COVID-19 pandemic despite decreased rates of vaccination during this time. HPV vaccine series completion was significantly lower than COVID-19 vaccine series completion, highlighting a need to improve HPV vaccine completion counseling. Additionally, patient education should address the knowledge gap discovered regarding the link between HPV infection and oropharyngeal cancer.

[Anogenital warts-An update]. / Anogenitalwarzen ­ ein Update.

With a prevalence of around 1% in the sexually active population anogenital warts are the most frequent human papillomavirus (HPV)-related disease. In the vast majority of cases the underlying cause of the infection is due to HPV types 6 and 11. The diagnosis can usually be clinically established but in certain cases a histopathological work-up can be useful. Buschke-Lowenstein tumors represent such a scenario. The current therapeutic armamentarium for anogenital warts ranges from surgical ablative procedures up to local immunomodulatory treatment. All procedures have different advantages and disadvantages and are relatively time-consuming and sometimes also unpleasant for the patient. Anogenital warts are also a possible expression of an incomplete immunological control of HPV. Therefore, it should be emphasized that for certain affected individuals, especially immunosuppressed patients, special attention should be given to ensuring that screening investigations for HPV-associated dysplasia is carried out according to the respective valid guidelines. The primary prophylaxis by vaccination of girls and boys prior to first HPV exposure represents a very effective option to drastically reduce the prevalence of anogenital warts and other HPV-related diseases.

The effect of theoretical and student-centered interactive education on intern nursing students' knowledge and consideration regarding human papillomavirus and its vaccine in Turkey: A repeated measures design.

Background: Intern nursing students not only belong to the high-risk group for human papillomavirus (HPV) infection and its associated complications but also represent the future healthcare workforce. Therefore, they constitute a significant group that should comprehensively understand HPV and its vaccine. Objective: This study aimed to assess the impact of educational interventions on intern nursing students' knowledge and considerations related to HPV and its vaccine. Methods: A repeated measures design with pretest/posttest measures was employed. The study involved 88 students at a university in Turkey and was conducted between November 2021 and February 2022. Data were collected using a Personal Information Form and the HPV Information Scale. All participants received theoretical and student-centered interactive education, and data were analyzed using numerical data, percentage distributions, Bonferroni correction, and one-way repeated measures ANOVA. Results: The total score of the scale and the scores of all four sub-dimensions obtained in the first and third months after the education were significantly higher than those obtained before the education (p <0.001). Additionally, the proportion of students considering getting an HPV vaccine increased following the education (p <0.001).Conclusions: The education on HPV and its vaccine potentially improved students' knowledge levels and increased consideration for vaccination. Implementing interventions that equip nursing students with sufficient knowledge about HPV and its vaccine can contribute to reducing HPV-related cancer rates. Therefore, it is recommended to implement educational programs focused on the prevention of HPV-related cancers.

Comparing the Costs and Diagnostic Outcomes of Replacing Cytology with the QIAsure DNA Methylation Test as a Triage within HPV Primary Cervical Cancer Screening in The Netherlands.

Detecting hypermethylation of tumour suppressor genes could provide an alternative to liquid-based cytology (LBC) triage within HPV primary cervical screening. The impact of using the QIAsure® FAM19A4/mir124-2 DNA Methylation Test (QIAGEN, N.V, Hilden, Germany) on CIN3+ diagnoses, retention, unnecessary colposcopies, and programme costs is unknown. A decision-tree model was developed to compare LBC with the QIAsure Methylation testing to guide colposcopy referral. Incorporating clinician- and self-sampling pathways the model was informed by the Dutch cervical cancer screening programme, published studies, and manufacturer data. Clinical and cost outcomes were assessed using two scenarios for DNA methylation testing and LBC relative performance. Sensitivity analyses (deterministic and probabilistic) were performed to assess model and parameter uncertainty. A range of self-sampling uptake was assessed in scenario analyses. For the screening cohort (n = 807,269) where 22.1% self-sampled, the number of unnecessary colposcopies and CIN3+ diagnoses varied according to the relative performance of methylation testing and LBC. Irrespective of relative performance, the cost per complete screen was lower and fewer people were lost to follow-up when using DNA methylation testing. The results indicate that, within an HPV primary screening programme that incorporates self-sampling, using the QIAsure Methylation Test for triage reduces the cost per screen compared to LBC.

[Oral HPV infection in HIV-positive persons from Corrientes, Argentina]. / Infecciones orales por VPH en personas HIV positivas de Corrientes, Argentina.

INTRODUCTION: Oral cavity HPV infections are associated with a subgroup of cancers whose prevalence is increasing worldwide. HIV infected people are in an increased risk of contracting HPV infection and developing cancer. The present study reveals the frequency and genotypic variability of this virus in the oral cavity and its association with probable risk factors in an HIV+ population of the province of Corrientes. METHODS: Mouthwashes were taken from 133 participants. After DNA extraction, the presence of HPV was detected by nested PCR. Positive cases were typed by reverse line blot or by sequencing. RESULTS: HPV was detected in 22% (29/133) of the mouthwashes. In 62% (18/29) of the positive samples, at least one high-risk genotype was detected. Participants older than 36 years (p = 0.03, aOR = 3.2, CI = 1.1-9.4) and a viral load of more than 40 copies (p = 0.04, aOR = 3.3, CI = 1.1-10.3) had higher risk of infection by any HPV genotype. In relation to the age of initiation of sexual intercourse, it was a significant parameter in the case of patients with infections by high-risk genotypes (p = 0.04, aOR = 7.2, IC = 1.6-32.3). In addition, previously unreported low-risk genotypes were observed in the oral cavity of inhabitants of the region like HPV-13 and HPV-114. DISCUSSION: Collecting baseline epidemiological data in this type of vulnerable population helps to clarify the natural history of the virus in extragenital locations and focus on regional particularities that allow the development of health policies in accordance with the magnitude of the regional problem.

Introducción: Las infecciones por virus del papiloma humano (VPH) en cavidad oral se asocian a un subgrupo de cánceres cuya prevalencia está en incremento en todo el mundo. Las personas portadoras HIV (PHIV) tienen un mayor riesgo de contraer una infección por VPH y eventualmente desarrollar cáncer. El presente estudio trata de relevar la frecuencia y variabilidad genotípica de dicho virus en cavidad oral y su asociación con probables factores de riesgo en una población HIV+ de la provincia de Corrientes. Métodos: Se tomaron enjuagados bucales de 133 participantes. Luego de la extracción de ADN se detectó por PCR anidada la presencia de VPH. Los casos positivos se tipificaron por Reverse Line Blot y por secuenciación. Resultados: En la serie analizada se detectó una frecuencia global de VPH del 22% (29/133) en los enjuagados bucales. El 62% (18/29) de los casos positivos presentó al menos un genotipo de alto riesgo. Los participantes con más de 36 años (p = 0.03, aOR = 3.2, IC = 1.1-9,4) y una carga viral de más de 40 copias/mL (p = 0.04, aOR = 3.3, IC = 1.1-10.3) reflejaron mayor riesgo de infección por VPH. La edad de inicio de relaciones sexuales también resultó un indicador útil en los casos que presentaron infecciones por genotipos de alto riesgo (p = 0.04, aOR = 7.2, IC = 1.6-32.3). Además, se observaron genotipos de bajo riesgo no reportados con anterioridad en cavidad oral de habitantes de la región (VPH-13 y VPH-114). Discusión: Relevar datos epidemiológicos basales en poblaciones vulnerables y altamente expuestas a VPH ayuda a clarificar la historia natural del virus en localizaciones extragenitales y a focalizarnos en particularidades regionales que permitan elaborar políticas de salud acordes a la magnitud del problema local.

Estandarización de PCR en tiempo real para detección y cuantificación de los oncogenes E7 de seis Virus del Papiloma Humano de Alto Riesgo

El cáncer de cuello uterino es causado por la infección persistente del epitelio cervical con los genotipos de alto riesgo del Virus del Papiloma Humano. Para su detección se realizan pruebas moleculares que detectan el gen L1 del VPH. Este gen puede perderse hasta en el 11 % de los casos durante la integración del ADN viral en el genoma del hospedero originando falsos negativos. Por otra parte, el oncogén E7 se expresa durante todas las etapas de progresión de la enfermedad. El objetivo de este trabajo fue estandarizar una PCR en tiempo real del oncogén E7 (E7-qPCR) para genotipificación y cuantificación de 6 VPH-AR. Los resultados muestran que la E7- qPCR amplificó VPH-16, -18, -31, -33, -35 y -45 con una alta sensibilidad con límites de detección desde 102 copias, eficiencias entre 90 y 110 %, valores R2 > 0,97 y análisis de curva de fusión que revelan productos específicos.

Cervical cancer is caused by persistent infection of the cervical epithelium with the high-risk genotypes of the Human Papilloma Virus (HR-HPV). For its detection, molecular tests are carried out that detect the L1 gene of HPV. This gene can be lost in up to 11 % of cases during the integration of viral DNA into the host genome, causing false negatives. On the other hand, the E7 oncogene is expressed during all stages of disease progression. The aim of this work was to standardize a real-time PCR of the E7 oncogene (E7-qPCR) for genotyping and quantification of 6 HR-HPV. The results show that the E7-qPCR amplified HPV-16, -18, -31, -33, -35 and -45 with high sensitivity with detection limits from 102 copies, efficiencies between 90 and 110 %, R2 values >0,97 and melting curve analysis revealing specific products.

Global prevalence of human papillomavirus-related oral and oropharyngeal squamous cell carcinomas: a systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review to determine the global prevalence of HPV in oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC). MATERIALS AND METHODS: Literature was searched through October 2022 in main databases to address the question "What is the global prevalence of Human Papillomavirus in oral and oropharyngeal cancer?" Studies had to identify HPV by PCR, ISH, or p16 immunohistochemistry to be eligible. Quality was assessed using the JBI checklist for prevalence studies. Meta-analyses were performed, and reporting followed PRISMA guidelines. RESULTS: Sixty-five studies were included, and most of them had methodological limitations related to sampling and the HPV detection tool. The pooled prevalence of HPV-positivity was 10% (event rate = 0.1; 95% CI: 0.07, 0.13; P < 0.01; I2 = 88%) in the oral cavity and 42% (event rate = 0.42; 95% CI: 0.36, 0.49; P = 0.02; I2 = 97%) in oropharynx. The highest HPV prevalence in OSCC was reached by Japan, meanwhile, in OPSCC, Finland and Sweden were the most prevalent. HPV16 is the genotype most frequent with 69% in OSCC and 89% in OPSCC, being the tonsils the intraoral location more affected by HPV (63%, p < 0.01, I2 76%). CONCLUSION: The evidence points to an apparent burden in HPV-related OPSCC, mostly in North America, Northern Europe, and Oceania, especially due to the HPV16 infection suggesting different trends across continents. CLINICAL RELEVANCE: This updated systematic review and meta-analysis provide sufficient evidence about the global HPV prevalence in OSCC and OPSCC and the most frequent HPV subtype worldwide.

Comparative Effects of Bivalent, Quadrivalent, and Nonavalent Human Papillomavirus Vaccines in The Prevention of Genotype-Specific Infection: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Human papillomavirus (HPV) infection is a major global disease burden and the main cause of cervical cancer. Certain HPV genotypes, with are the most common etiologic pathogens and cause a significant disease burden, are being targeted for vaccine development. However, few studies have focused on the comparative effectiveness of the bivalent HPV (2v-HPV), quadrivalent HPV (4v-HPV), and nonavalent HPV (9v-HPV) vaccines against HPV strain-specific infection. This study investigated the comparative effects of these vaccines against genotype-specific infection. MATERIALS AND METHODS: We conducted a pairwise and network meta-analysis of published randomized clinical trials of HPV vaccines according to sex and HPV infection status for nine HPV genotypes (HPV 6/11/16/18/31/33/45/52/58). RESULTS: Overall, 10 randomized controlled trials (12 articles) were included in this study. In the network meta-analysis, no statistically significant differences were observed in the prevention of carcinogenic HPV strains (16/18/31/33/45/52/58) between the 2v-HPV and 4v-HPV vaccines in female HPV infection-naïve populations. However, the 9v-HPV vaccine showed a significantly superior effect compared with 2v-HPV and 4v-HPV vaccines in preventing HPV 31/33/45/52/58 infections. Although 2v-HPV and 4v-HPV vaccines provided some cross-protection against HPV 31/33/45/52/58 infections, the effect was significant only on HPV 31 infection. For HPV 16 and 18, neither statistically significant nor small differences were found in the prevention of HPV infection among the 2v-HPV, 4v-HPV, and 9v-HPV vaccines. CONCLUSION: Our study complements previous understanding of how the effect of HPV vaccines differs according to the HPV genotype. This is important because HPV genotype prevalence varies among countries. We advocate for continued efforts in vaccinating against HPV, while public health agencies should consider the difference in the vaccine effect and HPV genotype prevalence when implementing HPV vaccination in public vaccination programs.

Human Papillomavirus Vaccine Completion by 13: A Quality Improvement Initiative in a Large Primary Care Network.

OBJECTIVE: Fewer than 40% of U.S. children complete the human papillomavirus (HPV) vaccine series before their 13th birthday. In our large pediatric primary care network, HPV vaccine completion rate by age 13 was 30%. We hypothesized that a phased quality improvement (QI) initiative would increase rates of HPV vaccine completion by age 13 across our network. METHODS: This QI initiative was conducted in a network of 30 practices located across two states, in urban and suburban settings, consisting of teaching and non-teaching clinics, and ranging in size from three to 50 providers per office. We used a phased approach incorporating multicomponent network-wide and iterative practice-specific interventions. Key interventions included: updating clinical decision support to default order HPV vaccine due at preventive visits starting at age nine instead of 11, data audit and feedback to providers and practices, encouraging use of a strong provider recommendation, and standing orders. RESULTS: From April 2019 to October 2022, HPV vaccine completion by age 13 across our network increased from 30% to 55% and met criteria for special cause variation on statistical process control charts. A gap in median HPV vaccine completion by age 13 between patients with public insurance and patients with private or commercial insurance decreased from 9% to 1%. CONCLUSION: A QI initiative was associated with a sustained increase in HPV vaccine series completion by age 13 and reduced variation in care across a large network of 30 primary care practices.

Multiparametric MRI-based radiomics model for predicting human papillomavirus status in oropharyngeal squamous cell carcinoma: optimization using oversampling and machine learning techniques.

OBJECTIVES: To develop and validate a multiparametric MRI-based radiomics model with optimal oversampling and machine learning techniques for predicting human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma (OPSCC). METHODS: This retrospective, multicenter study included consecutive patients with newly diagnosed and pathologically confirmed OPSCC between January 2017 and December 2020 (110 patients in the training set, 44 patients in the external validation set). A total of 293 radiomics features were extracted from three sequences (T2-weighted images [T2WI], contrast-enhanced T1-weighted images [CE-T1WI], and ADC). Combinations of three feature selection, five oversampling, and 12 machine learning techniques were evaluated to optimize its diagnostic performance. The area under the receiver operating characteristic curve (AUC) of the top five models was validated in the external validation set. RESULTS: A total of 154 patients (59.2 ± 9.1 years; 132 men [85.7%]) were included, and oversampling was employed to account for data imbalance between HPV-positive and HPV-negative OPSCC (86.4% [133/154] vs. 13.6% [21/154]). For the ADC radiomics model, the combination of random oversampling and ridge showed the highest diagnostic performance in the external validation set (AUC, 0.791; 95% CI, 0.775-0.808). The ADC radiomics model showed a higher trend in diagnostic performance compared to the radiomics model using CE-T1WI (AUC, 0.604; 95% CI, 0.590-0.618), T2WI (AUC, 0.695; 95% CI, 0.673-0.717), and a combination of both (AUC, 0.642; 95% CI, 0.626-0.657). CONCLUSIONS: The ADC radiomics model using random oversampling and ridge showed the highest diagnostic performance in predicting the HPV status of OPSCC in the external validation set. CLINICAL RELEVANCE STATEMENT: Among multiple sequences, the ADC radiomics model has a potential for generalizability and applicability in clinical practice. Exploring multiple oversampling and machine learning techniques was a valuable strategy for optimizing radiomics model performance. KEY POINTS: • Previous radiomics studies using multiparametric MRI were conducted at single centers without external validation and had unresolved data imbalances. • Among the ADC, CE-T1WI, and T2WI radiomics models and the ADC histogram models, the ADC radiomics model was the best-performing model for predicting human papillomavirus status in oropharyngeal squamous cell carcinoma. • The ADC radiomics model with the combination of random oversampling and ridge showed the highest diagnostic performance.

A Model for Empowering Rural Solutions for Cervical Cancer Prevention (He Tapu Te Whare Tangata): Protocol for a Cluster Randomized Crossover Trial.

BACKGROUND: Maori are the Indigenous people of Aotearoa (New Zealand). Despite global acceptance that cervical cancer is almost entirely preventable through vaccination and screening, wahine Maori (Maori women) are more likely to have cervical cancer and 2.5 times more likely to die from it than non-Maori women. Rural Maori residents diagnosed with cervical cancer have worse outcomes than urban residents. Living in rural Aotearoa means experiencing barriers to appropriate and timely health care, resulting from distance, the lack of community resourcing, and low prioritization of rural needs by the health system and government. These barriers are compounded by the current screening processes and referral pathways that create delays at each step. Screening for high-risk human papillomavirus (hrHPV) and point-of-care (POC) testing are scientific advances used globally to prevent cervical cancer. OBJECTIVE: This study aims to compare acceptability, feasibility, timeliness, referral to, and attendance for colposcopy following hrHPV detection between a community-controlled pathway and standard care. METHODS: This is a cluster randomized crossover trial, with 2 primary care practices (study sites) as clusters. Each site was randomized to implement either pathway 1 or 2, with crossover occurring at 15 months. Pathway 1 (community-controlled pathway) comprises HPV self-testing, 1-hour POC results, face-to-face information, support, and immediate referral to colposcopy for women with a positive test result. Pathway 2 (standard care) comprises HPV self-testing, laboratory analysis, usual results giving, information, support, and standard referral pathways for women with a positive test result. The primary outcome is the proportion of women with hrHPV-positive results having a colposcopy within 20 working days of the HPV test (national performance indicator). Qualitative research will analyze successes and challenges of both pathways from the perspectives of governance groups, clinical staff, women, and their family. This information will directly inform the new National Cervical Screening Program. RESULTS: In the first 15-month period, 743 eligible HPV self-tests were performed: 370 in pathway 1 with POC testing and 373 in pathway 2 with laboratory testing. The positivity rate for hrHPV was 7.3% (54/743). Data collection for the second period, qualitative interviews, and analyses are ongoing. CONCLUSIONS: This Maori-centered study combines quantitative and qualitative research to compare 2 clinical pathways from detection of hrHPV to colposcopy. This protocol draws on rural community practices strengths, successfully engaging Maori from a whanau ora (family wellness) approach including kanohi ki te kanohi (face-to-face), kaiawhina (nonclinical community health workers), and multiple venues for interventions. It will inform the theory and practice of rural models of the use of innovative technology, addressing Maori cervical cancer inequities and facilitating Maori wellness. The findings are anticipated to be applicable to other Indigenous and rural people in high-income countries. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12621000553875; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12621000553875. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51643.