Oral Human Papillomavirus Infection Research Articles

Mhealth interventions to improve public knowledge of HPV-associated oral cancer in the UK

In the UK, the age-standardised incidence rates of cancers of the ‘oropharynx’and ‘lip and oral cavity’ are ‘2.6%’ and ‘4.9%’ respectively.These indicate a significant oral cancer burden. These are attributable tonumerous risk factors; the major risk factors include tobacco use, alcoholconsumption, and exposure to oral HPV infection. Though, significantsuccess in reducing the prevalence of most of the major risk factorshas been recorded, exposure to HPV infection still remains a majordriver of oral cancer prevalence in the UK. HPV-associated oropharyngealcancer prevalence in men and women is 6.29 and 2.04%, respectively,while prevalence for HPV-associated oral cavity cancer in menand women is 11.7 and 6.95%, respectively; and it is projected to overtakecervical cancer by the year 2025. This is mainly due to exposure tooral HPV infection through oral sex practice as over 63% of UK youngadults are found to have a history of oral sex practice. Only a minorityof the UK population is aware of HPV-associated oral cancer whichcalls for more public health efforts to increase knowledge on the role ofHPV in oral cancer. While the use of technology-based, clinic-based,and community-based interventions has been employed to improvepublic knowledge on the role of HPV in oral cancer development, technology-based interventions have not been adequately explored. Mhealthapplication-based interventions have been previously employed toimprove knowledge and behavioural change in diverse chronic diseases.Hence, our recommendation on the adoption of Mhealth application-based intervention strategy in the education of the UK’s populationon HPV-associated oral cancer is highly desirable as it closelyaligns with the country’s National Health Service (NHS) commitmenttowards the digital transformation of the healthcare system.

A cross-sectional study of the association of dental health factors with progression and all-cause mortality in men diagnosed with HPV-associated oropharyngeal cancer

BackgroundHuman Papillomavirus-associated oropharyngeal cancer (HPV-OPC) incidence is increasing among men in the United States. Poor dental health has previously been associated with risk of head and neck cancers, oral HPV infection, and persistence but it is not understood whether dental health is associated with outcomes. We sought to determine the association of dental health with progression free survival and overall mortality among men with an HPV-OPC.MethodsA cross sectional study of men diagnosed with HPV-OPC between 2014–2020 at Moffitt Cancer Center in Tampa, FL was conducted. Dental records were abstracted for assessment of dental fitness prior to cancer treatment. Five dental factors including number of teeth lost, pocket depth, gingival score, loss of attachment, and bone loss were individually examined. Risk factor and outcome data were collected from a patient risk questionnaire and medical record. Using item response theory, an overall dental fitness score from five dental factors was developed in which missing data were multiply imputed. Cox proportional hazards model was used to assess whether dental factors were associated with progression-free survival or overall mortality.ResultsAmong 206 HPV-OPC cases, median follow-up was 3.4 years (IQR: 2.4–4.4) during which 40 cases involved progression or mortality and 25 deaths occurred. Overall dentition was significantly associated with progression free survival (p = 0.04) and with overall survival (p = 0.03) though findings were not significant after adjustment for age at diagnosis, stage, and smoking history (p = 0.146 and p = 0.120, respectively). A pocket depth of 7 mm or more was associated with overall survival (HR: 5.21; 95% CI: 1.43—19.11) and this remained significant after adjustment for confounding (aHR: 4.14; 95% CI: 1.72—16.26).ConclusionsAmong men diagnosed with an HPV-associated OPC in the US, worse dental health was associated with reduced progression free survival and overall survival, but not after adjustment for confounders. Further studies are needed to examine whether dental health is associated with other prognostic factors and subsequent treatment-related outcomes.

Prevalence and Determinants of Cervicovaginal, Oral, and Anal Human Papillomavirus Infection in a Population of Transgender and Gender Diverse People Assigned Female at Birth.

Purpose: The human papillomavirus (HPV) causes cervicovaginal, oral, and anogenital cancer, and cervical cancer screening options include HPV testing of a clinician-collected sample. Transgender and gender diverse (TGD) people assigned female at birth (AFAB) face many barriers to preventive care, including cancer screening. Self-sampling options may increase access and participation in HPV testing and cancer screening. This study estimated the prevalence of HPV in self-collected cervicovaginal, oral, and anal samples from Midwestern TGD individuals AFAB. Methods: We recruited TGD individuals AFAB for an observational study, mailing them materials to self-collect cervicovaginal, oral, and anal samples at home. We tested samples for high-risk (HR; 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) and other HPV genotypes (6, 11, 66, 68, 73, 90) using a polymerase chain reaction mass array test. Prevalence ratios for HPV infection at each site as a function of participant characteristics were estimated in log-binomial models. Results: Out of 137 consenting participants, 102 completed sample collection. Among those with valid tests, 8.8% (HR = 6.6%; HPV 16/18 = 3.3%) were positive for oral HPV, 30.5% (HR = 26.8%; HPV 16/18 = 9.7%) for cervicovaginal HPV, and 39.6% (HR = 33.3%; HPV 16/18 = 8.3%) for anal HPV. A larger fraction of oral (71.4%) than anal infections (50.0%) were concordant with a cervicovaginal infection of the same type. Conclusions: We detected HR cervicovaginal, oral, and anal HPV in TGD people AFAB. It is essential that we reduce barriers to cancer screening for TGD populations, such as through the development of a clinically approved self-screening HPV test.

Analogies between HPV Behavior in Oral and Vaginal Cavity: Narrative Review on the Current Evidence in the Literature.

Human genital papilloma virus infection is the most prevalent sexually transmitted infection in the world. It is estimated that more than 75% of sexually active women contract this infection in their lifetime. In 80% of young women, there is the clearance of the virus within 18-24 months. In developed countries, oral squamous cell carcinoma (OSCC) is now the most frequent human papilloma virus (HPV)-related cancer, having surpassed cervical cancer, and it is predicted that by 2030 most squamous cell carcinomas will be the HPV-related rather than non-HPV-related form. However, there are currently no screening programs for oral cavity infection. While the natural history of HPV infection in the cervix is well known, in the oropharynx, it is not entirely clear. Furthermore, the prevalence of HPV in the oropharynx is unknown. Published studies have found wide-ranging prevalence estimates of 2.6% to 50%. There are also conflicting results regarding the percentage of women presenting the same type of HPV at two mucosal sites, ranging from 0 to 60%. Additionally, the question arises as to whether oral infection can develop from genital HPV infection, through oral and genital contact or by self-inoculation, or whether it should be considered an independent event. However, there is still no consensus on these topics, nor on the relationship between genital and oral HPV infections. Therefore, this literature review aims to evaluate whether there is evidence of a connection between oral and cervical HPV, while also endorsing the usefulness of the screening of oral infection in patients with high-risk cervical HPV as a means of facilitating the diagnosis and early management of HPV-related oral lesions. Finally, this review emphasizes the recommendation for the use of the HPV vaccines in primary prevention in the male and female population as the most effective means of successfully counteracting the increasing incidence of OSCC to date.

HIV-Related Oral Mucosa Lesions: A Cross-Sectional Study on a Cohort of Italian Patients.

Human immunodeficiency virus (HIV) infection can be associated with oral mucosal diseases, including oral candidiasis and HPV infection, which are putative indicators of the immune status. This retrospective cross-sectional study was aimed at assessing the prevalence of HIV-related oral mucosal lesions in a cohort of Italian HIV+ patients regularly attending the Clinics of Infectious Diseases. One hundred seventy-seven (n = 177) patients were enrolled and 30 (16.9%) of them showed HIV-related diseases of the oral mucosa. They were mainly found in male patients over 35 years old, undergoing Combination Antiretroviral Therapy (cART), and with CD4+ count < 500/µL. Oral candidiasis was the most common HIV-related oral lesion. No significant correlations could be detected between the prevalence of HPV infection and other clinical parameters (lymphocyte count, cART treatment and viral load). HIV-related oral mucosal diseases can correlate with immunosuppression. Early diagnosis and management of oral lesions in HIV+ patients should be part of the regular follow-up, from a multidisciplinary perspective of collaboration between oral medicine and infectious disease specialists, in an attempt to reduce morbidity due to oral lesions and modulate antiretroviral therapy according to the patient's immune status.

Prevalence of oral human papillomavirus infection among the general adult population in Hong Kong.

A cross-sectional study in 2021-23 collected oral rinse gargle samples from an human papillomaviruses(HPV) vaccine-naïve general adult population in Hong Kong. HPV was detected by a PCR using SPF10 primers, and genotyped by a linear array covering 25 genotypes. Epidemiologic information including sociodemographics, medical history, oral health, and sexual behavior were collected by a self-administered questionnaire. Altogether, 2323 subjects aged 18-75 (median 47) years with 50.1% male were recruited. The prevalence for oral HPV infection with all genotypes combined, high-risk, and low-risk genotypes was 1.5%, 0.7%, and 0.7%, respectively; and with no statistically significant difference between participant gender. The prevalence increased with age and was highest in women at 45-54 years (2.7% for all genotypes combined), and highest in men aged >64 years (4.1% for all genotypes combined). HPV52 was the most common genotype among all participants. Univariate analysis suggested more lifetime sexual or oral sexual partners as risk factors, but they did not reach statistical significance upon multivariate analysis; whereas higher educational level had an independent protective effect. To conclude, oral HPV prevalence increased with age in Hong Kong. Strategies to prevent oral HPV infection and the associated cancers are urgently needed.

Association of oral microbiome with oral human papillomavirus infection: a population study of the National Health and Nutrition Examination Survey, 2009-2012.

Oral human papillomavirus(HPV) infection and the oral microbiome are associated with oropharyngeal cancer. However, population-based data on the association of oral microbiome with oral HPV infection are limited. We performed a cross-sectional analysis of 5,496 participants aged 20-59 in National Health and Nutrition Examination Surveys(NHANES):2009-2012. The association between either oral microbiome alpha diversity or beta diversity and oral HPV infection was assessed using multivariable logistic regression or principal coordinate analyses(PCoA) and multivariate analysis of variance(PERMANOVA). For alpha diversity, we found a lower number of observed Amplicon sequence variants(ASVs) (adjusted odds ratio[aOR] = 0.996; 95%CI = 0.992-0.999) and reduced Faith's Phylogenetic Diversity(aOR = 0.95; 95%CI = 0.90-0.99) associated with high-risk oral HPV infection in the overall population. This trend was observed in males for both high-risk and any oral HPV infection. Beta diversity showed differentiation of oral microbiome community by high-risk oral HPV infection as measured by Bray-Curtis dissimilarity (R2 = 0.054%; P = .029) and unweighted UniFrac distance (R2 = 0.046%; P = .045) among the overall population, and associations were driven by males. Both oral microbiome alpha diversity(within-sample richness and phylogenetic diversity) and beta diversity(heterogeneous dispersion of oral microbiome community) are associated with HPV infection. Longitudinal studies are needed to characterize the role of the microbiome in the natural history of oral HPV infection.

Investigating oral human papillomavirus co-infection with Neisseria gonorrhoeae and Chlamydia trachomatis.

Compared to cervical cancer, little is known about human papillomavirus (HPV)-driven oropharyngeal cancer and their cofactors. Here, we investigated potential associations between Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) with oral HPV and HPV persistence, which are known cofactors in cervical carcinogenesis, and also play a role in HPV-driven oropharyngeal cancer. Saliva samples (n=547) from 312 people were tested for CT and NG and whom had previously been tested for oral HPV infection in a longitudinal study. Eight participants were positive for CT (2.6%) and one for NG (0.3%). Six of these nine participants were also positive for oral HPV in at least one of their samples. We found no significant associations between HPV, CT, or NG infection in the saliva samples analyzed. These preliminary data suggest CT and NG have little influence on oral HPV-positivity and persistence in a general population. However, larger studies focusing on 'at risk' population cohorts are necessary to assess potential associations between oral sexually transmissible infections and oral HPV infections, and their outcomes.

Implications of oral dysbiosis and HPV infection in head and neck cancer: from molecular and cellular mechanisms to early diagnosis and therapy.

Head and neck cancer (HNC) is the sixth most common type of cancer, with more than half a million new cases annually. This review focuses on the role of oral dysbiosis and HPV infection in HNCs, presenting the involved taxons, molecular effectors and pathways, as well as the HPV-associated particularities of genetic and epigenetic changes and of the tumor microenvironment occurred in different stages of tumor development. Oral dysbiosis is associated with the evolution of HNCs, through multiple mechanisms such as inflammation, genotoxins release, modulation of the innate and acquired immune response, carcinogens and anticarcinogens production, generation of oxidative stress, induction of mutations. Thus, novel microbiome-derived biomarkers and interventions could significantly contribute to achieving the desideratum of personalized management of oncologic patients, regarding both early diagnosis and treatment. The results reported by different studies are not always congruent regarding the variations in the abundance of different taxons in HNCs. However, there is a consistent reporting of a higher abundance of Gram-negative species such as Fusobacterium, Leptotrichia, Treponema, Porphyromonas gingivalis, Prevotella, Bacteroidetes, Haemophilus, Veillonella, Pseudomonas, Enterobacterales, which are probably responsible of chronic inflammation and modulation of tumor microenvironment. Candida albicans is the dominant fungi found in oral carcinoma being also associated with shorter survival rate. Specific microbial signatures (e.g., F. nucleatum, Bacteroidetes and Peptostreptococcus) have been associated with later stages and larger tumor, suggesting their potential to be used as biomarkers for tumor stratification and prognosis. On the other hand, increased abundance of Corynebacterium, Kingella, Abiotrophia is associated with a reduced risk of HNC. Microbiome could also provide biomarkers for differentiating between oropharyngeal and hypopharyngeal cancers as well as between HPV-positive and HPV-negative tumors. Ongoing clinical trials aim to validate non-invasive tests for microbiome-derived biomarkers detection in oral and throat cancers, especially within high-risk populations. Oro-pharyngeal dysbiosis could also impact the HNCs therapy and associated side-effects of radiotherapy, chemotherapy, and immunotherapy. HPV-positive tumors harbor fewer mutations, as well as different DNA methylation pattern and tumor microenvironment. Therefore, elucidation of the molecular mechanisms by which oral microbiota and HPV infection influence the HNC initiation and progression, screening for HPV infection and vaccination against HPV, adopting a good oral hygiene, and preventing oral dysbiosis are important tools for advancing in the battle with this public health global challenge.

Oral Inflammation and Human Papilloma Virus Association among Hispanics.

Identifying factors related to persistent human papillomavirus (HPV) infection is essential to reduce the incidence of HPV-related cancers. To evaluate whether gingival/periodontal inflammation is associated with oral HPV infection. This cross-sectional study (n = 740) uses data from the follow-up visit of the San Juan Overweight Adults Longitudinal Study, which recruited overweight/obese adults aged 40-65 from Puerto Rico. Participants completed a dental examination and two interviews (face-to-face/ACASI) and provided oral rinse samples for HPV detection. Oral inflammation was assessed using two definitions: (1) the number of sites with bleeding on probing (BOP), and (2) the number of teeth with probing pocket depths (PPD) ≥ 4 mm and BOP. Multivariate logistic regression was used to assess the association between oral inflammation and oral HPV. Nearly three-quarters (72%) of participants were female, and 68% had 50 years or older. Participants with HPV had a higher mean number of sites with BOP (15.5 vs. 10.1) and teeth with PPD ≥ 4 mm and BOP (8.5 vs. 3.2) than participants without HPV (p < 0.05). After adjusting for sex, age, income, and the number of oral sex partners, the odds of having an oral HPV infection increased by 3% (95% confidence interval (CI): 1.00-1.06) for any additional sites with BOP and 5% (95% CI: 1.02-1.09) for any other teeth with PPD ≥ 4 mm and BOP. We found that oral inflammation was associated with oral HPV infection among adults in Puerto Rico. Future studies need to further investigate the underlying mechanisms.

Abstract B130: Social determinants associated with HPV disparities among people with HIV infection in Puerto Rico

Abstract Background: People with HIV (PWH) have a higher risk of acquiring oral HPV infection when compared to people without HIV, which can lead to the high prevalence of oropharyngeal cancers in PWH. Puerto Rico (PR), a US jurisdiction, is on the top 10 in terms of HIV prevalence and cumulative AIDS cases among the US and have a significant burden and disparity of HPV-related malignancies. Additionally, PR has socio-economic disadvantages, which is a social determinant of oral health disparities, and can potentially affect oral HPV. The relationship of these social determinants with HPV have not been investigated in PWH in PR. Hence, in this study, we evaluated the relationship between socio-economic, behavioral, and oral health factors with oral HPV among PWH. Methods: We evaluated 117 sexually active PWH (102 males and 15 females) from a community clinic in San Juan, PR. Oral rinse samples were collected and analyzed for HPV infection and genotype using the DNA ELISA kit HPV SPF10 and RHA kit HPV SPF10-LiPA25. We collected sociodemographic characteristics (age, marital status, employment, income) as well as lifestyle variables (smoking habits, alcohol consumption, sexual practices) through an administered questionnaire. Participants also underwent a clinical full-mouth periodontal assessment following the CDC/AAP guidelines. Statistical analyses in relation to HPV were performed in R statistical software. Findings: There was a prevalence of oral HPV infection of 29.9% in PWH in PR, which 70% were high-risk genotypes, with HPV-18 being the most abundant genotype (27.5%). There were 33.3% of males who had oral HPV while only 20% of females had oral HPV. Also, oral HPV infection was significantly associated with periodontitis (p&amp;lt;0.05). In men, oral HPV positivity trended to be frequent with no HPV vaccination (p=0.08). No HPV vaccination was associated with lower income (p&amp;lt;0.05). There was no association between HPV status and sociodemographic and lifestyle variables. Interpretation: The prevalence in high-risk HPV genotypes among PWH was higher than what has previously been observed in PR. We also found a higher prevalence of HPV-18, which may explain clinical disparities concerning oropharyngeal cancer in PR’s population. Additionally, our findings highlight the importance of access to medical care in low-resource settings. Low income can be a surrogate of lack of access of care, which can impact early diagnosis, risk, and prevention of oral HPV. Therefore, targeting social determinants, may help lower the risk of infection and oral cancer in underserved populations. While our findings contribute to understanding the impact of social determinants in oral cancer, more studies are still needed that investigate the relationship between other sociodemographic factors that affect oral health in PWH. Citation Format: Carlos A. Solá-Morlá, Yabdiel Ramos-Valerio, Coral Martes-Villalobos, María M. Sánchez-Vázquez, Ramón F. Gonzalez-García, Ana P. Ortiz, Magaly Martinez-Ferrer, Josué Pérez-Santiago. Social determinants associated with HPV disparities among people with HIV infection in Puerto Rico [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B130.

Cervical Cancer Screening Coverage at Tertiary Care Institutes Across India.

The 70% screening coverage target proposed in the global cervical cancer elimination strategy is not achieved even at tertiary centres in India. A situational analysis was done to assess the currently existing facilities and barriers in tertiary care institutes. This cross sectional multicentric study was conducted from August to September 2021 in six tertiary care institutes across India. Women aged 30-49 years attending outpatient services (OPD) were invited for cervical screening. Women and health care professionals (HCPs) were administered structured questionnaires to assess knowledge, attitude and practices regarding cervical cancer screening services. Out of 6709 eligible women who attended OPD, 1666 (24.8%; range:19-57%) received screening. Availability of screening kits was limited to 10-25 Pap/HPV tests per day. Visual inspection with acetic acid (VIA) and HPV testing were offered only at certain centres. Colposcopy and treatment facilities were optimal at all centres. Knowledge, attitude and practices were analysed for 1800 women: 45.7% had heard of cervical cancer, 78.0% did not know that it is preventable, 75.8% never heard about screening. Common symptoms correctly identified included postmenopausal bleeding (4.8%), postcoital bleeding (5.7%), intermenstrual bleeding (5.8%) and vaginal discharge (12.4%). Risk factors were identified by minority: poor menstrual hygiene (6.6%), oral contraceptive pill use (6.4%), multiparity (4.4%), and HPV infection (3.0%). Out of 21, mean total knowledge score (MTKS) was 2.07± 2.67. Out of 317 HCPs, 96.5% knew that cervical cancer is caused by HPV infection, is preceded by premalignant stage, and that it is preventable by screening and treatment (80.1%). Knowledge about screening modalities was present in 87.4% for cytology, 75.1% for VIA, 68.8% for HPV test. MTKS of HCPs was 20.88±6.61 out of 32. Even at tertiary centres, limited availability of HPV tests, reluctance to implement VIA and lack of awareness among women remain the major barriers.

Risk Factors for the Anal and Oral Human Papillomavirus (HPV) Infections among Women with Severe Cervical Lesions: A Prospective Case-Control Study.

The carcinogenicity of HPV infection in the anogenital and oropharyngeal regions is broadly accepted. The aim of the study was to define risk factors for anal and oral HPV infections in high-risk patients with biopsy-proven severe cervical lesions (CIN2+). Altogether immunocompetent 473 females with CIN2+ were categorized into the study group and another 245 women into the control group. The strongest risk factor for anal HPV infection was the presence of cervical HPV infection (p < 0.001). Furthermore, ten or more lifetime sexual partners (p = 0.013), a sexual non-coital contact with the anal area (p < 0.001), and actively practicing anal-penetrative intercourse (p < 0.001) were significantly associated with anal HPV. A history of genital warts in the woman (p = 0.010) and the presence of genital warts in the male partner (p = 0.029) were found statistically significant for the risk of oral HPV infection. Our data suggest that the presence of HPV infection, especially high-risk genotypes, in one anatomical site poses the greatest risk for HPV infection in another anatomical site. The cervix is the main reservoir of infection, but the risk factors for anal and oral HPV infections are dissimilar according to different anatomical distances and more complex routes of transmission.

Prevalence and risk factors of oral human papillomavirus infection among 4212 healthy adults in Hebei, China

BackgroundHuman papillomavirus (HPV) infection is an essential cause of oropharyngeal squamous cell carcinoma that is increasing in incidence worldwide. However, little is known about the epidemiology of oral HPV infection among healthy adults in China.MethodsA study in northern China was conducted in 2021 as baseline data of Diverse Life-Course Cohort (DLCC). Residents who aged above 20 were eligible to participate. Oral swab specimens and questionnaires were collected from 4226 participants. HPV DNA in oral exfoliated cells was tested by Nested Polymerase Chain Reaction approach and sequencing. Univariate and multivariate analyses were performed to assess the associations between exposure factors and oral HPV infection.ResultsOverall prevalence of oral HPV infection was 4.08% (95%CI, 3.69%-4.68%). The most prevalent HPV type detected was HPV-81 (1.35%; 95% CI, 1.00%–1.70%), followed by HPV-16 (0.64%; 95% CI, 0.40%–0.88%). Oral HPV infection presented a bimodal pattern with respect to age in male and female participants. Oral HPV prevalence of male participants was significantly higher than prevalence of female participants (5.0% versus 3.6%, P = 0.041). Prevalence of oral HPV was higher among current smokers (OR = 1.59; 95% CI, 1.11–2.29; P = 0.039) and current drinkers (OR = 1.60; 95% CI, 1.14–2.25; P = 0.023). Current alcohol consumption was independently associated with oral HPV infection (OR = 1.74; 95% CI, 1.22–2.50; P = 0.010).ConclusionsAmong healthy adults aged above 20 in Hebei, China, the prevalence of high-risk HPV infection was 1.92% (95%CI, 1.51%-2.34%). Oral HPV prevalence was independently associated with alcohol consumption. More tailored prevention strategies are needed to prevent oral HPV infection through smoking cessation, reduction of alcohol consumption, and HPV vaccination.

Global health trends of human papillomavirus‐associated oral cancer: A review

AbstractOral cancer is a malignant neoplastic disease, it constitutes the most common cancer in the head‐and‐neck region, and it is the 16th most common and 15th deadliest cancer type affecting humans. Despite the global efforts channelled towards global cancer control, the burden of oral cancer is still increasing. Every year, several thousands of people across 195 countries/territories die of oral cancer, and only about 40%–50% of the victims of oral cancer barely survive for 5 years after diagnosis. Within the past few decades, there has been a paradigm shift in the epidemiological trend of oral cancer risk factors. Oral sex – a major route of transmission of human papillomavirus (HPV) – was found to be increasing at an alarming rate, whereas tobacco and alcohol use had been on the decline. This narrative review critically discussed the contemporary challenges facing the global eradication of HPV‐associated oral cancer, with reasonable recommendations. The challenges discussed in this review are major, ranging from clinical to public health policy issues, which include the lack of validated and inexpensive oral HPV screening and diagnostic tools, high global public illiteracy on oral HPV infection, diverse sociocultural factors, weak global research capacity on oral HPV infection and HPV‐associated oral cancer and the absence of policies across different countries on national preventive programmes on HPV‐associated oral cancer. This review also identified the need for more attention towards the prevention and control oral HPV infection and HPV‐associated oral cancers globally.

Risk factors for malignant oral mucosal lesion development (literature review). Part 1. Endogenous and biological factors

Relevance. Oral mucosal cancer (OMC) is the sixteenth most common cancer worldwide. The high mortality rate is mainly due to the asymptomatic course of the disease in the early stages and late detection when the tumour process poorly responds to treatment. Determining the impact of various risk factors and establishing their relationship are necessary to prevent and diagnose malignant oral mucosal lesions in the early stages.Purpose. Based on the modern literature, the study aimed to determine the impact value of various internal and external risk factors on malignant oral mucosal lesion development and assess the risk factors’ relationship.Material and methods. The research material included the analysis of literature from databases – Elsevier, PubMed, Elibrary, Google Academy, Medline and Cyberleninka. The study included literature sources in Russian and English.Results. Based on modern literature, we have determined endogenous and biological risk factors for malignant oral mucosal lesion development. The study noted the high role of microbiome changes and the presence of dysbiosis in patients with malignant neoplasms and proved the direct involvement of Candida fungi in carcinogenesis. The development of oral mucosal cancer and the presence and severity of oral yeast colonization and human papillomavirus infection showed a positive correlation. Chronic oral diseases, which are susceptible to malignant transformation or contribute to the development of carcinomas, have been identified, and their relationship has been established with biological risk factors, age, sex of the patient and duration of the disease course.Conclusion. The studies considered in this part of the review prove the influence of endogenous and biological factors on the development of malignant neoplasms of the oral cavity and determine their relationship. However, many mechanisms remain unexplored to date. Effective primary and secondary prevention implementation needs improvement and the development of a multidisciplinary approach to research methodology, study the complex impact of all groups of risk factors on the development of malignant oral mucosal lesions.

Abstract PR06: Cooperative HPV and YAP-mediated oncogenic reprogramming of oral progenitors into cancer stem cells at single cell resolution

Abstract Human papillomavirus-positive head and neck squamous cell carcinoma (HPV+HNSC) constitutes the most common HPV-driven malignancy in the United States, and yet the molecular and cellular mechanisms underlying carcinogenesis in HPV+HNSC remain poorly understood. The decades long latency period and incomplete penetrance linking oral HPV infection to HPV+HNSC suggest that oncogenic events beyond E6-E7 expression are required for carcinogenesis. YAP is a transcriptional co-activator that coordinates cell stemness, growth, proliferation, and survival. We previously identified alterations resulting in YAP activation as a potential oncogenic event in HNSC. We thus hypothesized YAP activation in the context of E6-E7 expression may represent a key tumor initiating event leading to HPV+HNSC. We developed a genetically engineered murine system to investigate the effects of local induction of YAP activation and E6-E7-expression in Keratin14+ (K14+) oral epithelial progenitor cells (OEPCs). In this system, intralingual administration of tamoxifen and dietary administration of doxycycline enables spatiotemporally controlled expression of E6-E7 and/or YAP. Employing this model, we identify combined E6-E7 and YAP activation (E+Y) as sufficient to induce highly penetrant carcinoma formation as early as 10 days after transgene induction. Immunofluorescent analyses showed E+Y resulted in the ectopic expansion of a mitotically active (Ki67+), stem-like (TP63+, SOX2+) epithelial cell population with invasive potential. Bulk RNAseq of microdissected tongue epithelia showed that E+Y uniquely induced transcriptional programs promoting cell cycle progression, epithelial cell plasticity, and acute inflammatory response, which were not observed upon sole activation of either the E6-E7 or YAP transgene. scRNAseq of transgene-induced tongue epithelial cell suspensions identified 8 distinct clusters, including previously defined physiologic oral epithelial cell states and novel transgene-associated clusters. E+Y resulted in the emergence of a unique epithelial cell cluster with transcriptional characteristics consistent with a cancer stem cell population, with enrichment in YAP, mTORC1, E2F, and MYC-driven programs, and pan-cancer cell states including cell cycle, hypoxia, squamous differentiation, and partial EMT. Implantation of E+Y cells resulted in tumor formation in 100% of NSG mice, indicating that E+Y drives the emergence of a cancer stem cell population. We next defined transcriptionally co-expressed modules driving E+Y tumor initiating capacity. Among TCGA-HNSC subjects, 8 of 12 modules were enriched in tumor compared to matched normal tissue. Interestingly, 3 modules (G1/S, cell migration, and focal adhesion) were associated with overall and disease-free survival. Our findings show YAP activation in the context of E6-E7 expression is sufficient for rapid carcinogenesis. We illuminate cellular processes driving malignant conversion at single cell resolution, and show enrichment of these processes in human HNSC exhibiting poor prognosis. Citation Format: Farhoud Faraji, Sydney I. Ramirez, Lauren M. Clubb, Kuniaki Sato, Paola Y. Anguiano Quiroz, William M. G. Galloway, Thomas S. Hoang, Kate Medetgul-Ernar, Pauline Marangoni, Alfredo A. Molinolo, Joseph A. Califano, Quinton Smith, Ophir D. Klein, Pablo Tamayo, J. Silvio Gutkind. Cooperative HPV and YAP-mediated oncogenic reprogramming of oral progenitors into cancer stem cells at single cell resolution [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PR06.

Epidemiology of oral human papillomavirus infection among diverse Chinese adults in typical areas of China: Findings from the DLCC study.

Human papillomavirus (HPV) infection is a predominant cause of oropharyngeal squamous cell carcinoma. However, there is limited knowledge about the epidemiology of oral HPV infections among adults in China. We collected data from a prospective cohort that enrolled participants in mainland China. A total of 9867 participants aged at least 20 years provided oral swab specimens in typical areas of China (Hebei and Guangdong provinces) in 2021. HPV DNA in oral exfoliated cells was tested using Nested Polymerase Chain Reaction and sequencing. Prevalence among sub-populations was compared. Multivariable logistic regression models were employed to assess possible factors influencing oral HPV infection. The overall prevalence of oral HPV infection was 3.0% [95% confidence interval (CI):2.68%-3.36%]. Among those infected, 1.3% (1.08%-1.53%) were infected with high-risk HPV types. Men had a higher age-standardized HPV infection prevalence (3.6%, 2.96-4.29%) compared to their female counterparts (2.7%, 2.35-3.12%). People in Hebei had a higher age- and sex-standardized prevalence (4.1%, 3.50%-4.70%) than those in Guangdong (2.2%, 1.80%-2.56%). Generally, men (odds ratio [OR] and 95% CI: 1.42, 1.09-1.85) and people in Hebei (2.01, 1.53-2.65) had higher odds of any type of HPV infection. Additionally, people living in urban areas had a 2.15-fold (1.43-3.26) higher odds of high-risk HPV infection. This study reveals a low prevalence of oral HPV infection with significant geographic and sex differences among Chinese population. This is the first study to report the epidemiological characteristics of oral HPV infection among Chinese adults in diverse geographic areas with large sample size.

Oral Human Papillomavirus Prevalence and Genotyping Among a Healthy Adult Population in the US

In the US, oropharyngeal cancer, predominantly caused by high-risk (HR) human papillomavirus (HPV) infection, is the most frequent HPV-associated cancer, surpassing cervical cancer. However, little is known about oral HPV prevalence and genotype distribution in the general population. To assess oral HPV prevalence and factors associated with HR and low-risk infection in a general US population. PROGRESS (Prevalence of Oral HPV Infection, a Global Assessment) was a cross-sectional observational study conducted between November 2021 and March 2022 in 43 dental offices in the US (24 urban, 13 urban cluster, and 6 rural sites), spanning 21 states. Eligible participants were aged 18 to 60 years, visiting dental clinics for routine dental examination. Dental clinics used targeted sampling to recruit equal distributions of men and women and across age groups. Participants provided an oral gargle specimen for HPV DNA and genotyping and completed behavioral questionnaires, and dentists reported oral health status. Detection of HPV DNA and genotyping was performed using the SPF10/DEIA/LiPA25 system at a central laboratory. Oral HPV prevalence. Of the 3196 participants enrolled, mean (SD) age was 39.6 (12.1) years, and 55.5% were women. Oral HPV prevalence was 6.6% (95% CI, 5.7%-7.4%) for any HPV genotype, and 2.0% (95% CI, 1.5%-2.5%), 0.7% (95% CI, 0.4%-1.0%), and 1.5% (95% CI, 1.1%-1.9%) for HR, HPV-16, and 9-valent-HPV vaccine types, respectively. Among HPV-positive participants, HPV-16 was the most prevalent genotype (12.4% among men and 8.6% among women). Prevalence of HPV was higher in men than women and highest among men aged 51 to 60 years (16.8%, 6.8%, and 2.1% for any HPV, HR HPV, and HPV-16, respectively). Factors associated with HR oral infection included being male (adjusted odds ratio [AOR], 3.1; 95% CI, 1.2-8.5), being aged 51 to 60 years (AOR, 3.3; 95% CI, 1.5-7.3), having 26 or more lifetime male sex partners (AOR, 6.5; 95% CI, 2.3-18.7), and having 6 to 25 lifetime female oral sex partners (AOR, 3.4; 95% CI, 1.3-8.7). In this cross-sectional study, oral HPV burden was highest among older men who may be at higher risk of developing oropharyngeal cancer. In addition to male sex and older age, HR oral HPV infection was also associated with sexual behaviors, including increasing number of male sex partners and female oral sex partners.

Natural History of Oral HPV Infection among Indigenous South Australians.

This study aims to describe the natural history of and identify the risk factors associated with oral human papillomavirus (HPV) infections in an Australian Indigenous cohort. A longitudinal cohort study design, with baseline (2018), 12-month, and 24-month data obtained from Indigenous Australians aged 18+ years in South Australia, was performed. Face-to-face interviews were conducted, and saliva samples for HPV testing were collected at each time point. Basic descriptive analyses were conducted to calculate prevalence, incidence, persistence, clearance, and incidence proportions of any HPV infection. Multivariable logistic regression analyses with adjusted prevalence ratios (PRs) were conducted to identify risk factors associated with oral HPV infection. Among 993 participants with valid saliva samples, 44 HPV types were identified. The prevalence of infection with any oral HPV infection was 51.3%, high-risk HPV was 11%, and types implicated in Heck's disease (HPV 13 or 32) was 37.4%. The incidence, persistence, and clearance of any and high-risk HPV infections were 30.7%, 11.8% and 33.3% vs. 9.3%, 2.8%, and 9%, respectively. Our findings indicate that the prevalence, incidence, and persistence of oral HPV infection in a large sample of Indigenous Australians were high, and clearance was low. Oral sex behaviours and recreational drug use were risk factors associated with incident high-risk HPV infection.