Exploring the potential impact of human papillomavirus on infertility and assisted reproductive technology outcomes.

Human papillomavirus (HPV) is a common sexually transmitted disease that has been linked to both cancer and reproductive health issues. While its impact on fertility and pregnancy success has been studied, there is still too little evidence about the influence of HPV on assisted reproductive technology (ART). Therefore, there exists a need for HPV testing in couples undergoing infertility treatments. Infertile men have been found to have a higher prevalence of seminal HPV infection, which can compromise sperm quality and reproductive function. As such, it could be important to investigate the correlation between HPV and ART outcomes in order to improve the quality of evidence. Understanding the potentially detrimental effects of HPV on ART outcomes may have promising important implications for the management of infertility. This minireview summarizes the so far limited developments in this area and highlights the major need for further well-designed studies to address this issue.

Oral human papillomavirus (HPV) infection and HPV vaccination in an Australian cohort.

Human papillomavirus (HPV)-related oropharyngeal cancer (OPC) is increasing in incidence, yet very little is known about oral HPV infection in the general population. In this Australian-based study we assess oral HPV prevalence according to HPV vaccination status. Participants of the Oral Diversity Study were Australian residents, aged 18 to 70 years, who filled out a questionnaire about lifestyle and sexual behaviour, and donated a saliva sample in 2020 to 2021. We obtained permission to access HPV vaccination status through record linkage with the Australian Immunisation Register. Saliva samples were DNA extracted, DNA quality checked and analysed for HPV. We recruited 1023 participants to the Oral Diversity Study. Nine hundred twenty-one returned a saliva sample for analysis, 911 passed the DNA quality check and were included in the study. The oral HPV prevalence was 7.2%, and was strongly associated with sexual behaviours. We identified 27 different HPV types; 53% of participants carried high-risk HPV types, with no difference between the vaccinated and the unvaccinated groups (53% both, P = .979). Two hundred thirty participants (26%) were HPV vaccinated. The oral prevalence of the nine HPV types included in the nonavalent HPV vaccine was significantly lower in the vaccinated participants compared to the unvaccinated (0.9% vs 3.4%; P = .022). These findings suggest that a sizeable minority of Australian residents harbour oral HPV infections, and many of these are high-risk subtypes. We found some evidence that HPV vaccination resulted in lower prevalence of oral HPV infections of vaccine-specific types. Larger surveys are required to confirm these findings.

Development and psychometric properties of the human papillomavirus-quality of life (HPV-QoL) questionnaire to assess the impact of HPV on women health-related-quality-of-life.

PURPOSE: The HPV-Quality-of-Life (HPV-QoL) questionnaire was developed to determine the impact of Human-Papillomavirus (HPV) infection and related interventions on women health-related quality-of-life. This study provides the development and preliminary psychometric properties of a novel HPV-QoL questionnaire for adult women with HPV. METHODS: After reviewing literature and cognitive debriefing interviews in women who had experienced HPV-related conditions, instrument items and domains were developed. A draft questionnaire was pilot tested for comprehension and ease of completion. Psychometric evaluation of the final HPV-QoL scale was conducted in a psychometric study including 252 adult women derived to our centre by a positive HPV test in the cervical cancer screening program and/or presenting genital warts. RESULTS: The present study reveals that the HPV-QoL questionnaire, structured in four domains: general well-being [including psychological well-being and social well-being subdomains], health, contagiousness and sexuality, showed good metric properties of feasibility irrespective of age or educational level, and time to administer was less than 5 min. Internal consistency and temporal stability (reliability) showed values above the acceptable standards. The instrument showed its concurrent validity by means of a significant correlation with mental and sexual existing instruments; GHQ-12 and FSFI questionnaires, respectively, and also known groups validity showing significant differences among the subgroups regarding either sexual dysfunction or mental deterioration. CONCLUSION: This study provides an HPV-QoL questionnaire with an innovative patient-reported outcomes specific measurement tool to assess HRQoL in women with HPV infection. The present study suggests this questionnaire has satisfactory psychometric properties, including validity and reliability. Results support the use of the HPV-QoL questionnaire as a HRQoL measurement instrument for daily medical practice and clinical research.

Low Rates of Dual-Site and Concordant Oral-Cervical Human Papillomavirus Infections and Cancers: A Systematic Review.

Objective: The oral-cervical human papillomavirus (HPV) infection/cancer relationship is not well established. Oral-cervical HPV studies were reviewed to assess dual-site occurrence, HPV type concordance, and study quality/deficiencies. Methods: PubMed, EMBASE, Ovid Medline, and Web of Science were searched between 1/1/1990 and 8/10/2021 for studies investigating HPV infections/cancers and type concordance between the oral cavity/oropharynx and cervix. Dual-site and concordant HPV infection rates were summarized as percentages; cancer diagnoses studies were summarized using standardized incidence ratios (SIR). The Quality Assessment Tool for Quantitative Studies (QATQS) evaluated study methodology. Results: One hundred fourteen papers were identified. Most were cross-sectional (n=79, 69%), involved synchronous dual-site HPV testing (n=80, 70%), did not report HPV type concordance (n=62, 54%), and achieved moderate methodological QATQS ratings (n=81, 71%). The overall dual-site infection rate averaged 16%; the HPV type concordance rate averaged 41%, among those dually-infected women. Most HPV-related cancer diagnoses studies reported increased secondary cancer risk, with SIRs generally ranging from 1.4 to 29.4 for secondary cervical cancer after primary oral cancer and from 1.4 to 6.3 for secondary oral cancer after primary cervical cancer. Conclusion/Impact: Oral-cervical HPV infections/cancers remain understudied. Future research should use stronger methodologies and HPV concordance analyses to better understand oral-cervical HPV epidemiology.

Sexual debut and association with oral human papillomavirus infection, persistence and oropharyngeal cancer-An analysis of two Australian cohorts.

Oropharyngeal cancer is increasingly caused by human papillomavirus (HPV), and this increase is believed to be caused by changing sexual behaviour. It has been hypothesised that an immune response to HPV through sexual intercourse is much stronger than an immune response elicited from oral sex. Therefore, people who have their debut of oral sex before or at the same time as sexual intercourse would have a weaker immune response to HPV and hence be more likely to develop a persistent oral HPV infection and oropharyngeal cancer. Drake et al (Cancer. 2021;127[7]:1029-1038) found some evidence that supported this hypothesis. We have reanalysed two of our Australian cohorts with similar data in order to provide a perspective of Drake and colleagues' publication, as sexual behaviour varies depending on culture and geographical location. We found that engaging in oral sex (OR 4.46, 95% CI [1.88-10.62]) and being younger than 20 years at oral sex debut (OR 9.46, 95% CI [3.53-25.31]) were both very strong risk factors for oropharyngeal cancer. Participants in the general population cohort who had their sexual intercourse debut before the age of 18 were more likely to be oral HPV positive (OR 2.69, 95% CI [1.50-4.83]). Oral sex debut before sexual intercourse debut was quite uncommon in our two Australian cohorts. However, timing of or sexual debuts may further add to risks of oropharyngeal cancer, and future studies should be designed to investigate timing and order of sexual debuts to help clarify the roles of these potential causal factors.

Genetic Drivers of Head and Neck Squamous Cell Carcinoma: Aberrant Splicing Events, Mutational Burden, HPV Infection and Future Targets.

Head and neck cancers include cancers that originate from a variety of locations. These include the mouth, nasal cavity, throat, sinuses, and salivary glands. These cancers are the sixth most diagnosed cancers worldwide. Due to the tissues they arise from, they are collectively named head and neck squamous cell carcinomas (HNSCC). The most important risk factors for head and neck cancers are infection with human papillomavirus (HPV), tobacco use and alcohol consumption. The genetic basis behind the development and progression of HNSCC includes aberrant non-coding RNA levels. However, one of the most important differences between healthy tissue and HNSCC tissue is changes in the alternative splicing of genes that play a vital role in processes that can be described as the hallmarks of cancer. These changes in the expression profile of alternately spliced mRNA give rise to various protein isoforms. These protein isoforms, alternate methylation of proteins, and changes in the transcription of non-coding RNAs (ncRNA) can be used as diagnostic or prognostic markers and as targets for the development of new therapeutic agents. This review aims to describe changes in alternative splicing and ncRNA patterns that contribute to the development and progression of HNSCC. It will also review the use of the changes in gene expression as biomarkers or as the basis for the development of new therapies.

Natural history of oral HPV infection: Longitudinal analyses in prospective cohorts from Australia.

Oral infection with human papillomavirus (HPV) is likely to underpin the rapidly rising incidence of oropharyngeal squamous cell carcinoma; however, there are few data describing the natural history of oral HPV infection. We recruited 704 participants aged 20 to 70 years from worksites, universities and primary care practices in Brisbane, Australia. Participants completed questionnaires at baseline, 12 and 24 months and donate four saliva samples at baseline, 6, 12 and 24 months for HPV polymerase chain reaction testing and typing. We estimated the prevalence of oral HPV infection at baseline, incidence of new infections among those HPV-negative at baseline, clearance rate and persistent infections. At baseline, 10.7% of participants had oral HPV infections from 26 different HPV types. Sexual behaviours were associated with oral HPV infection, including more partners for passionate kissing (29 or more; odds ratio [OR] 3.4, 95% confidence interval [CI] 1.5-8.0), and giving and receiving oral sex (16 or more; OR 5.4, 95% CI 1.6-17.7 and OR 5.6, 95% CI 1.6-18.7, respectively). Of 343 participants, HPV-free at baseline and with subsequent saliva samples, 87 (25%) acquired new infections over the 24 months. Sixty-eight of 87 people included in the clearance analysis (78%) cleared their oral HPV infections. Clearance was associated with being a nonsmoker (OR 12.7, 95% CI 1.3-122.8), and no previous diagnosis of a sexually transmitted infection (OR 6.2, 95% CI 2.0-19.9). New oral infections with HPV in this sample were not rare. Although most infections were cleared, clearance was not universal suggesting a reservoir of infection exists that might predispose to oropharyngeal carcinogenesis.

Prevalence and genotypes of human papilloma virus infection in CIN3 in Beijing, China.

BACKGROUND: To investigate the incidence of single and multiple human papillomavirus (HR-HPV) infection in CIN3 patients before operation. METHODS: The complete clinical data of patients with CIN3 by biopsy were collected. HPV23 typing in the first 3 months of the treatment was detected. The infection rate of HPV was analyzed. RESULTS: One thousand and fifty-one HPV subtypes were detected in 679 patients with HPV (+) CIN3 with primary conization, of which the top ten were HPV16, 33, 31, 58, 6, 52, 18, 43, 51, 11, 68, respectively. Among them, single subtype HPV infection accounted for 64.36%, while multiple HPV infection accounted for 35.64%. For multiplex HPV infection, there were 2, 3, 4 species, and 148 (21.80%), 69 (10.16%), 16 (2.36%), 9 (1.33%) cases of multiple HPV infection of 5 and above HPV subtypes respectively. The incidence of multiple HPV infection in CIN3 patients in 2015 was higher than that in 2012 (39.01% vs. 30.08%, P=0.019), and the proportion of multiple infections in HPV was higher than that in the 2014 group. CONCLUSIONS: The top 10 HPV subtypes of the CIN3 patients were included in HPV nine valence vaccines except HPV43 and 51.

Programmed Death-Ligand 1 Expression, Microsatellite Instability, Epstein-Barr Virus, and Human Papillomavirus in Nasopharyngeal Carcinomas of Patients from the Philippines.

Most nasopharyngeal carcinomas (NPCs) in a high-incidence population are driven by Epstein-Barr virus (EBV) infection. EBV-associated malignancies have increased expression of the programmed death-ligand 1 (PD-L1). Immunotherapy agents targeting the PD-1/PD-L1 pathway have achieved durable treatment effects in patients with various cancer types including EBV-associated malignancies. In this study, we sought to investigate PD-L1 expression in a cohort of patients with NPCs from the Philippines. Fifty-six NPCs were studied for PD-L1, p16, and DNA mismatch repair (MMR) deficiency by immunohistochemistry. One case with MMR deficiency was also assessed for microsatellite instability (MSI) by polymerase chain reaction. EBV and human papillomavirus (HPV) status were tested by in situ hybridization. All NPCs were p16 negative. Three of the 56 NPCs (5%) were EBV negative (EBV-) and HPV negative, while one NPC (1/56, 2%) was EBV positive and showed MSI (EBV+/MSI). Positive PD-L1 expression (PD-L1+), defined as membranous staining in ≥1% tumor cells, was seen in 64% (36/56) of NPCs. All three EBV- NPCs were PD-L1+ as was the EBV+/MSI NPC. PD-L1+ was seen significantly more often in NPCs from non-smokers than those from smokers (23/28, 82% vs 9/18, 50%; P = 0.047). PD-L1+ was not associated with pT, pN, distant metastasis, or clinical stage (P > 0.05). PD-L1+ was not associated with overall survival (P = 0.473). In summary, our results show frequent PD-L1 expression in NPCs regardless of EBV status and a preferential PD-L1 expression in non-smokers. MSI and HPV positivity are exceedingly rare in NPCs.

An exploration of individual- and population-level impact of the 2-dose HPV vaccination schedule in pre-adolescent girls.

Since 2014, several countries have implemented a 2-dose schedule for Human papillomavirus (HPV) vaccination. Licensure of the 2-dose schedule was based on non-inferiority results from immunobridging studies, comparing the antibody levels of the 2-dose schedule in young girls to those of the 3-dose schedule in young adults. Since licensure, additional data on antibody levels and other aspects of the immune response and clinical effectiveness have become available. This review will discuss the current outcomes on immunogenicity and effectiveness together with an exploration on the population impact of 2-dose schedules from a cost-effectiveness perspective. The 2-dose schedule has important benefits, such as easier logistics, reduced expenditure, potentially higher acceptance and fewer side effects. Policymakers and registration authorities should consider whether these benefits outweigh the likely differences on individual- and population-level impact between the 2- and 3-dose schedules.