The Human Papillomavirus Enigma: A Narrative Review of Global Variations in Oropharyngeal Cancer Epidemiology and Prognosis.

Oropharyngeal cancers (OPCs) in Asia account for 42% of the global burden and over 50% of related deaths. Human papillomavirus (HPV) is involved in over 70% of OPC cases in the Western hemisphere, but its role in the Eastern hemisphere is unclear. This study reviews OPC epidemiology, including prevalence, etiological factors (such as smokeless tobacco and HPV), and their interaction. Among the SEAR countries, India had the highest incidence of HPV-related OPCs at 38.4%, while data were unavailable for most African countries, with only a 14% incidence reported. Conversely, the American region exhibited one of the highest HPV positivity rates, reaching up to 65% in different states of the USA, while Brazil reported an incidence of up to 38%. In the European Union, the UK had the highest incidence of HPV-associated OPC, reaching up to 52%. In the Western Pacific region, New Zealand demonstrated the highest incidence at up to 78%. Smokeless tobacco consumption was higher in SEAR countries, which had a relatively lower incidence of HPV infection, suggesting a negative correlation between the two. Based on our literature search, the most common detection methods used globally are immunohistochemistry for p16 and polymerized chain reaction. OPCs are a global health concern, and proper identification and classification are vital. HPV-driven cancers have better survival rates, emphasizing the need for focused research on specific problem areas based on the burden of HPV-positive or HPV-negative cancers.

HPV-driven oropharyngeal cancer burden in Paris and its region (ILE DE FRANCE) from 1981 TO 2021.

BACKGROUND: France has the sixth highest incidence of oropharyngeal cancer (OPC) in Europe, but the epidemiological impact of high-risk HPV (HR-HPV) remains poorly documented. The objective of our study was to assess the proportion of OPCs caused by HR-HPV in Paris, and its suburbs, over the four past decades. This area accounts for almost one-fifth of the total population of France. METHODS: OPCs diagnosed in 1981, 1986, 1991, 1996, 2001, 2006, 2011, 2016 and 2020/2021 in two of the main referral cancer centers for HNCs in Paris and its suburbs were retrieved from the tumor biobanks. HPV status was determined by p16-staining and HPV-DNA detection. Samples were considered HPV-driven if both assays were positive. Results were compared to the French cancer registry data. RESULTS: Samples from 697 OPC patients were assessed (including 82 % of all samples diagnosed in 2001, 2006, 2011, 2016, 2021). The proportion of HPV-driven cases rose from 2.7 % to 53 % between 1981 and 2021. HPV16 was the dominant genotype during the study period. Of patients with HPV-driven OPC, 81 % were male and 42 % were smokers versus 80 % and 92 % in their HPV-negative counterparts. The age of OPC patients increased significantly, during the study period, independent of their HPV status CONCLUSION: The proportion of HPV-driven OPCs has significantly increased in Paris and its suburbs, during the last four decades. OPCs has become the 2nd predominant type of head and neck cancer, in France. This may be linked to the rise in HPV-driven cases and the decrease of tobacco and alcohol consumption in men.

Psychosocial factors and patient and healthcare delays in large (class T3-T4) oral, oropharyngeal, and laryngeal carcinomas.

BACKGROUND: Psychosocial factors and socioeconomic status have been associated with incidence, survival, and quality of life among patients with head and neck cancer. We investigated the association between different psychosocial factors, socioeconomic status, and patient delays in T3-T4 oral, oropharyngeal, and laryngeal cancer. PATIENTS AND METHODS: We conducted a nationwide prospective questionnaire-based study (n = 203) over a 3-year period. RESULTS: We found no association between psychosocial factors (depression, social isolation, loneliness, and cynical hostility) and patient delay. Depression was three times more common among head and neck cancer patients compared with the general Finnish population. Head and neck cancer patients had lower educational levels and employment status, and were more often current smokers and heavy drinkers. CONCLUSIONS: Although we found no association between patient delay and psychosocial factors, patients diagnosed with a large head and neck cancer appeared to have a lower socioeconomic status and higher risk for developing depression, which should be considered in clinical practice.

Risk factors associated with oral Human Papillomavirus (HPV) prevalence within a young adult population.

BACKGROUND: The prevalence of, and risk factors for, genital Human Papillomavirus (HPV) infections within the young adult population are well-established; the same is not known for oral HPV. This observational study aimed to determine oral HPV prevalence and abundance within a UK young adult population, and examine if sexual practices and established risk factors of oropharyngeal squamous cell carcinomas (OPSCCs) (such as smoking and alcohol consumption) influenced HPV prevalence. METHODS: Convenience sampling was used to recruit a small sample of 452 UK-based young adults studying at a higher education (HE) institution to the study; the study was not powered. A highly sensitive real-time PCR HPV screening method was developed for the detection of multiple HPV subtypes from oral swabs. HPV-positive samples were subsequently screened by qPCR for viral subtypes HPV-6, HPV-11, HPV-16, HPV-18. Results were analysed by univariate and multivariate methods and stratified for gender, with lifestyle behaviour data collected via questionnaire. Socio-economic status was not captured within the questionnaire. RESULTS: We found a high oral HPV prevalence of 22.79%, with a dominance of high-risk viral type HPV-16 (prevalence 19.12%; abundance average 1.08 × 105 copies/million cells) detected within healthy young adults. Frequent smoking (p = .05), masturbation (p = .029), and engagement in multiple sexual activities (p = .057), were found to be associated with oral HPV prevalence, and HPV-16 prevalence, whilst behaviours traditionally associated with genital HPV were not. CONCLUSIONS: Our results strengthen the link between sexual practices and oral HPV transmission. We suggest that young adults should be considered high-risk for the contraction of oral HPV, although acknowledge that this sample of HE students may not be representative of the wider population. We show that high-risk HPV-16 is prevalent in the healthy population, as well as dominating within OPSCC; this study is one of the first to determine the dominance of oral HPV-16 prevalence and abundance within this population, presenting a clear need for greater awareness of oral HPV infections, and the risk factors for HPV-positive OPSCC within young adults.

Association between tonsillectomy and risk of oropharyngeal cancer: a systematic review.

Objective: Studies have demonstrated that tonsillectomy may alter the risk of oropharyngeal cancer (OPC). We systematically reviewed the evidence and pooled data to examine such an association. Methods: PubMed, Embase, and Scopus were searched up to 25th April 2023. Studies reporting an association between tonsillectomy and oropharyngeal cancer risk at any site were included. Results: Five studies were eligible. All examined the risk of tonsillar and base of the tongue (BOT) cancer with prior history of tonsillectomy. On meta-analysis of the data, prior history of tonsillectomy was associated with a significantly decreased risk of tonsillar cancer. The second meta-analysis showed that history of tonsillectomy did not significantly alter the risk of BOT cancer. However, after exclusion of one study, the results showed an increased risk of BOT cancer with a history of tonsillectomy. Conclusions: The scarce data available in the literature suggests that tonsillectomy may reduce the risk of tonsillar cancer but does not alter the risk of BOT cancer. Further studies are needed to explore the association between tonsillectomy and the risk of OPC.

Linking periodontitis with 20 cancers, emphasis on oropharyngeal cancer: a Mendelian randomization analysis.

While associations between periodontitis and an elevated risk of cancer have been suggested, the results of existing observational studies have been inconsistent, also leaving room for further investigation into the underlying mechanisms. This study was designed to delve into the possible causal link between periodontitis and 20 standard cancers while concurrently identifying potential mediators. We initiated a Mendelian randomization analysis that drew from either publicly accessible or personally obtained genome-wide association study (GWAS) datasets. The inverse variance weighting (IVW) method served as our primary tool for analysis. To ensure the strength and consistency of our results, we implemented additional strategies, including weighted median, weighted mode, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO), bolstered by funnel plots. Our analysis unveiled an elevated risk of head and neck cancer concomitant with periodontitis (p = 0.041, OR 0.999, 95% CI 0.999-1.000), specifically a heightened risk of oropharyngeal cancer (p = 0.022, OR 0.999, 95% CI 0.999-1.000). As a result of probing into potential mediators, Fusobacterium nucleatum emerged as a likely intermediary in the promoting effect of periodontitis on oropharyngeal cancer (p = 0.021, OR 0.999, 95% CI 0.998-1.000). Inversely, basal cell carcinoma and endometrial cancer demonstrated an association with an increased incidence of periodontitis (basal cell carcinoma: p = 0.020, OR 0.987, 95% CI 0.976-0.998; endometrial cancer: p = 0.027, OR 0.984, 95% CI 0.970-0.998). However, periodontitis exerted no significant causal impact on the 19 other common cancers or the three subtypes of head and neck cancer. To conclude, our results support the theory that periodontitis contributes to an enhanced risk of head and neck cancer, particularly oropharyngeal cancer, with Fusobacterium nucleatum functioning as a potential intermediary.

Human papillomavirus associated oropharyngeal cancer now the most common mucosal head and neck cancer in Queensland.

INTRODUCTION: The profile and outcomes of head and neck cancer throughout Australia has changed over the past decade. The aim of this study was to perform a population-based analysis of incidence, demographics, stage, treatments and outcomes of patients diagnosed with oropharyngeal squamous cell carcinoma (OPSCC), with a particular focus on HPV-associated disease. METHODS: This was a retrospective analysis of prospectively collected data within the Queensland Oncology Repository (QOR) and analysed by the Queensland Cancer Control Analysis Team. The cohort included patients diagnosed in Queensland between 1 January 2015 and 31 December 2019. Outcome measures included incidence of new OPSCC cases, age-standardised rates (ASR) (3-year average), demographics, p16 status, stage (8th Edition American Joint Commission on Cancer), treatments, and 2- and 5-year overall survival. RESULTS: There were 1527 newly diagnosed OPSCC, representing 96% (1527/1584) of all oropharyngeal cancers. It was the most common head and neck cancer diagnosed, with oral cavity cancer being the second most common (n = 1171). Seventy-seven percent were p16 positive (1170/1527), of which 87% (1019/1170) were male. The median age was 61 years and 49% (568/1170) presented with Stage I disease. The ASR was 6.3/100,000, representing a 144% incidence increase since 1982 (2.6/100,000). Radiotherapy was utilised in 91% of p16+ cases with 2- and 5- year overall survival of 89% and 79%, respectively. CONCLUSION: OPSCC is now the most common mucosal head and neck cancer diagnosed in Queensland, having surpassed oral cavity cancer. The majority are HPV-associated (p16+), presenting with early-stage disease with a favourable prognosis.

[Update: Epidemiology and Prevention of Oropharyngeal Cancer]. / Update: Epidemiologie und Prävention des Oropharynxkarzinoms.

Due to the association with the causal HPV-16 infection, the oropharyngeal carcinoma spreads into two separate entities depending on HPV-16 positivity. More recent data show a diversified picture of the importance and prevalence of the surrogate parameter p16 (discordance) for a definitive HPV-16 association, which varies worldwide. In the context of prevention options, vaccination is of major and HPV screening of healthy people only of little importance.

Antibodies against high-risk human papillomavirus proteins as markers for noncervical HPV-related cancers in a Black South African population, according to HIV status.

Human papillomavirus (HPV) proteins may elicit antibody responses in the process toward HPV-related malignancy. However, HPV seroepidemiology in noncervical HPV-related cancers remains poorly understood, particularly in populations with a high prevalence of human immunodeficiency virus (HIV). Using a glutathione S-transferase-based multiplex serology assay, antibodies against E6, E7 and L1 proteins of HPV16 and HPV18 were measured in sera of 535 cases of noncervical HPV-related cancers (anal (n = 104), vulval (n = 211), vaginal (n = 49), penile (n = 37) and oropharyngeal (n = 134)) and 6651 non-infection-related cancer controls, from the Johannesburg Cancer Study that recruited Black South African with newly diagnosed cancer between 1995 and 2016. Logistic and Poisson regression models were used to calculate adjusted odds ratios (aOR) and prevalence ratios (aPR) and 95% confidence intervals (CI) in cases versus controls. HPV16 E6 was more strongly associated with noncervical HPV-related cancers than HPV16 L1 or E7, or HPV18 proteins: anal (females (HPV16 E6 aOR = 11.50;95%CI:6.0-22.2), males (aOR = 10.12;95%CI:4.9-20.8), vulval (aOR = 11.69;95%CI:7.9-17.2), vaginal (aOR = 10.26;95%CI:5.0-21), penile (aOR = 18.95;95%CI:8.9-40), and oropharyngeal (females (aOR = 8.95;95%CI:2.9-27.5), males (aOR = 3.49;95%CI:1.8-7.0)) cancers. HPV16-E6 seropositivity ranged from 24.0% to 35.1% in anal, vulval, vaginal and penile cancer but was significantly lower (11.2%) in oropharyngeal cancer. After adjustment for HIV, prevalence of which increased from 22.2% in 1995-2005 to 54.1% in 2010-2016, HPV16 E6 seropositivity increased by period of diagnosis (aPR for 2010-2016 vs. 1995-2006 = 1.84;95%CI:1.1-3.0). Assuming HPV16 E6 seroprevalence reflects HPV attributable fraction, the proportion of certain noncervical-HPV-related cancers caused by HPV is increasing over time in South Africa. This is expected to be driven by the increasing influence of HIV.

Healthcare Utilization of Oral and Oropharyngeal Cancer Patients in Emergency Department and Outpatient Settings: An 8-year Population-Based Study.

INTRODUCTION: This study aimed to determine trends in the healthcare utilization by Oral Cavity and Oropharyngeal cancer patients across emergency department (ED) and outpatient settings in Alberta and examine the predictors of ED visits. METHODS: This is a retrospective, population-based, cohort study using administrative data collected by all healthcare facilities between 2010 and 2019 in Alberta, Canada. Trend of visits to different facilities, patients' primary diagnosis, and predictors of ED visits were analyzed. RESULTS: In total, 34% of patients had at least one cancer-related ED visit. With a rise of 31% in cancer incidence, there was a notable upswing in visits to outpatient clinics and community offices, while ED visits decreased. Cancer stage, rural residence, high material deprivation score, and treatments were found as predictors of ED visits. CONCLUSION: Improved symptom management and better care access for disadvantaged and rural oral cancer patients may decrease avoidable ED visits.

Population-level incidence of human papillomavirus-positive oropharyngeal, cervical, and anal cancers, by smoking status.

We estimated the population-level incidence of human papillomavirus (HPV)-positive oropharyngeal, cervical, and anal cancers by smoking status. We combined HPV DNA genotyping data from the Centers for Disease Control and Prevention's Cancer Registry Sentinel Surveillance System with data from the Kentucky Cancer Registry and Behavioral Risk Factor Surveillance System across smoking status. During 2004-2005 and 2014-2015 in Kentucky, most cases of oropharyngeal (63.3%), anal (59.7%), and cervical (54.9%) cancer were among individuals who ever smoked. The population-level incidence rate was higher among individuals who ever smoked than among those who never smoked for HPV-positive oropharyngeal (7.8 vs 2.1; adjusted incidence rate ratio = 2.6), cervical (13.7 vs 6.8; adjusted incidence rate ratio = 2.0), and anal (3.9 vs 1.6; adjusted incidence rate ratio = 2.5) cancers. These findings indicate that smoking is associated with increased risk of HPV-positive oropharyngeal, cervical, and anal cancers, and the population-level burden of these cancers is higher among individuals who ever smoked.

Clinical and prognostic differences in oropharyngeal squamous cell carcinoma in USA and Denmark, two HPV high-prevalence areas.

BACKGROUND: Uncertainty persists regarding clinical and treatment variations crucial to consider when comparing high human papillomavirus (HPV)-prevalence oropharyngeal squamous cell carcinoma (OPSCC) cohorts for accurate patient stratification and replicability of clinical trials across different geographical areas. METHODS: OPSCC patients were included from The University of Texas MD Anderson Cancer Center (UTMDACC), USA and from The University Hospital of Copenhagen, Denmark from 2015-2020, (n = 2484). Outcomes were 3-year overall survival (OS) and recurrence-free interval (RFI). Subgroup analyses were made for low-risk OPSCC patients (T1-2N0M0) and high-risk patients (UICC8 III-IV). RESULTS: There were significantly more HPV-positive (88.2 % vs. 63.1 %), males (89.4 % vs. 74.1 %), never-smokers (52.1 % vs. 23.7 %), lower UICC8-stage (I/II: 79.3 % vs. 68 %), and fewer patients treated with radiotherapy (RT) alone (14.8 % vs. 30.3 %) in the UTMDACC cohort. No difference in the adjusted OS was observed (hazard ratio [HR] 1.21, p = 0.23), but a significantly increased RFI HR was observed for the Copenhagen cohort (HR: 1.74, p = 0.003). Subgroup analyses of low- and high-risk patients revealed significant clinical and treatment differences. No difference in prognosis was observed for low-risk patients, but the prognosis for high-risk patients in the Copenhagen cohort was worse (OS HR 2.20, p = 0.004, RFI HR 2.80, p = 0.002). CONCLUSIONS: We identified significant differences in clinical characteristics, treatment modalities, and prognosis between a Northern European and Northern American OPSCC population. These differences are important to consider when comparing outcomes and for patient stratification in clinical trials, as reproducibility might be challenging.

Surveillance of human papillomavirus through salivary diagnostics - A roadmap to early detection of oropharyngeal cancer in men.

Human papillomavirus (HPV) is the most common sexually transmitted disease. Certain strains have the potential to cause malignancy in multiple anatomical sites if not cleared by the immune system. In most infected people, HPV is cleared within two years. However, HPV may persist in susceptible individuals with certain risk factors, eventually leading to malignancy. New evidence suggests that over 75% of all oropharyngeal cancers (OPC) are directly attributable to HPV. It is estimated that prophylactic HPV vaccination alone may take at least 25 years to have a significant impact on reducing the incidence of OPC. The temporal link between detection of oral HPV, persistence of the infection and the subsequent development of OPC have been well established. Moreover, men have threefold higher risk than women for acquiring HPV-OPC. This comprehensive review focuses on OPC development in men, highlighting the risk factors associated with malignant transformation of HPV-OPC. Current evidence is insufficient to determine whether early identification of at-risk demographics, screening, and prompt diagnosis result in improved outcomes. Hitherto, the effectiveness of an oral HPV screening program in this regard has not been investigated. Nevertheless, the potential to emulate the success of the cervical screening program remains a very real possibility.

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.

Trends and predictors of unplanned hospitalization among oral and oropharyngeal cancer patients; an 8-year population-based study.

PURPOSE: The incidence of oral cancers, particularly HPV-related oropharyngeal cancer, is steadily increasing worldwide, presenting a significant healthcare challenge. This study investigates trends and predictors of unplanned hospitalizations for oral cavity cancer (OCC) and oropharyngeal cancer (OPC) patients in the province of Alberta, Canada. METHODS: This retrospective, population-based, cohort study used administrative data collected from all hospitals in the province. Using the Alberta Cancer Registry (ACR), a cohort of adult patients diagnosed with a single primary OCC or OPC between January 2010 and December 2017 was identified. Linking this cohort with the Discharge Abstract Database (DAD), trends in hospitalizations, primary diagnoses, and predictors of unplanned hospitalization (UH) and 30-day unplanned readmission were analyzed. RESULTS: Of 1,721 patients included, 1,244 experienced 2,228 hospitalizations, with 48 % being categorized as UH. The UHs were significantly associated with a higher mortality rate, 18.5 % as compared to 4.6 % for planned, and influenced by sex, age groups, comorbidities, cancer types, stages, and treatment modalities. The rate of UH per patient decreased from 0.69 to 0.54 visits during the study period (P = 0.02). Common diagnoses for UH were palliative care and post-surgical convalescence, while surgery-related complications such as infection and hemorrhage were frequent in 30-day unplanned readmissions. Predictors of UH included cancer stage, material deprivation, and treatment, while cancer type and comorbidity predicted readmissions. CONCLUSION: The rate of UHs showed a noteworthy decline in this study, which could be a result of enhanced care coordination. Furthermore, identified primary diagnosis and predictors associated with UHs and readmissions, provide valuable insights for enhancing the quality of care for cancer patients.

CXCL9 mediating the effect of thyroid disorders on oral and oropharyngeal cancer risk: A mediation Mendelian randomization study.

INTRODUCTION: The established association between thyroid disorders (TD) and its two main subtypes-hyperthyroidism and hypothyroidism-and the incidence of oral and oropharyngeal cancer (OCPC) has been substantiated. However, the direct causal relationship and potential intermediary mechanisms linking these conditions have not been clearly defined in prior studies. MATERIAL & METHODS: This study employed univariate Mendelian randomization (MR) analysis to explore those relationship. Instrumental variables from genome-wide association study (GWAS) datasets for TD (n = 218,792), hyperthyroidism (n = 460,499), hypothyroidism (n = 213,990), and OCPC (n = 12,619), along with 41 intermediary inflammatory cytokines (n = 8293), were analyzed. Inverse variance weighting (IVW) method assessed the causal relationships, while summary MR analysis with pQTL datasets from decode and 91 inflammatory cytokines explored the cytokines' roles as biomarkers and therapeutic targets for OCPC. Multivariable MR (MVMR) analysis quantified the mediation effect of these cytokines in the TD-OCPC relationship. RESULTS: UVMR analysis provided strong evidence for a causal relationship between TD (OR = 1.376, 95 % CI = 1.142-1.656, p = 0.001), hyperthyroidism (OR = 1.319, 95 % CI=1.129-1.541, p = 0.001), hypothyroidism (OR = 1.224, 95 % CI = 1.071-1.400, p = 0.003), and the risk of OCPC. CXCL9 was identified as a significant intermediary in mediating the risk of OCPC from TD and its two subtypes (OR = 1.218, 95 % CI = 1.016-1.461, P = 0.033), suggesting its potential as a predictive biomarker for OCPC. MVMR analysis further revealed that CXCL9 mediated 7.94 %, 14.4 %, and 18 % of the effects of TD, hyperthyroidism, and hypothyroidism on OCPC risk, respectively. DISCUSSION: This study not only elucidated the potential causal relationships between TD including its two subtypes and OCPC risk, but also highlighted CXCL9 as a pivotal mediator in this association.

HPV-related oropharyngeal carcinoma remains infrequent over 25 years in a Brazilian Oral Pathology Center: A cross-sectional study with literature review.

BACKGROUND: The aim was to evaluate the frequency, clinicopathological features, and HPV status of oropharyngeal squamous cell carcinoma (OP-SCC) and benign HPV-related epithelial lesions of the oropharynx over the last 25 years. Moreover, a literature review was performed to investigate HPV frequency in OP-SCC samples diagnosed in Brazilian Centers. MATERIAL AND METHODS: A cross-sectional study analyzed OP-SCC, squamous papilloma, verruca vulgaris, and condyloma accuminatum, diagnosed from 1997 to 2021. HPV status of OP-SCC was determined by immunohistochemistry and "in situ" hybridization. Bivariate statistics were performed (p≤0.05). For the literature review, MEDLINE/PubMed, Web of Science, EMBASE, and Scopus were searched. Two independent reviewers assessed the studies for eligibility. RESULTS: Cross-sectional: 211 OP-SCC (63.0%) and 124 benign lesions (37.0%) were included. OP-SCC frequency increased gradually over time, whereas benign lesions had steady trends. OP-SCC affected more males (n= 171; 81.0%), though the relative frequency in females rose over time. Smoking (n= 127; 60.2%) was common in OP-SCC. Nineteen OP-SCC (13.0%) were positive for HPV. HPV-positive and HPV-negative tumors had similar clinicopathological features (p>0.05). Benign lesions predominated in middle-aged (n= 32; 26.7%) women (n= 71; 57.3%), in the soft palate (n=101; 81.5%). LITERATURE REVIEW: 32 studies were included, and in 60% of them, HPV frequency in OP-SCC was less than 25%. CONCLUSIONS: OP-SCC prevalence has been increasing, and it was mostly associated with smoking and alcohol rather than with HPV infection in Brazil. Benign lesions had a stationary frequency over the evaluated period.

Oncogenic Oral Human Papillomavirus Clearance Patterns over 10 Years.

BACKGROUND: Effective screening for oropharyngeal cancer is lacking. Four oncogenic HPV clearance definitions were explored to understand long-term natural history for persistent oncogenic oral HPV (oncHPV), the precursor of oropharyngeal cancer. METHODS: Prospective multicenter cohort of participants living with/at-risk for HIV, with oral rinse and gargle samples collected every 6 to 12 months for up to 10 years and tested for oncHPV. HPV clearance definitions included 1 (clear1), 2 (clear2), 3 (clear3) consecutive negatives, or being negative at last two visits (clearlast). RESULTS: Median time to clearance of oncHPV exceeded 2 years for conservative definitions (clear3: 2.38, clearlast: 2.43), but not lenient (clear1: 0.68, clear2: 1.15). By clear3, most incident infections cleared at 2, 5, 8 years (55.1%, 75.6%, 79.1%), contrary to prevalent infections (37.1%, 52.5%, 59.5%, respectively). In adjusted analysis, prevalent oncHPV, older age, male sex, and living with HIV were associated with reduced clearance. Of 1,833 subjects screened, 13.8% had prevalent oncHPV and 47.5% of those infections persisted ≥5 years, representing 6.5% of persons screened. Two men with prevalent oral HPV16 developed incident oropharyngeal cancer [IR = 1.62 per 100 person-years; 95% confidence interval (CI), 0.41-6.4]. Many with oral HPV16 persisted ≥5 years (and/or developed HPV-oropharyngeal cancer) among those with 2 (72.2%), ≥2 of first 3 (65.7%), or 3 (80.0%) consecutive positive oHPV16 tests, but not after 1 (39.4%). CONCLUSIONS: In our 10-year study, most incident infections cleared quickly. However, half of prevalent oncHPV persisted ≥5 years, suggesting increased risk with persistent oncHPV at >2 visits. IMPACT: We identified groups with persistent oncHPV at increased risk of oropharyngeal cancer and contextualized risk levels for those with oral HPV16 infection.

HPV-Related Oropharyngeal Cancer in Southern Thailand: Proportion Trend and Survival Outcome.

BACKGROUND: Persistent high-risk human papillomavirus (HPV) infection is one of the major etiologies of oropharyngeal squamous cell carcinoma (OPSCC). This study aimed to determine the proportion, temporal trend, and prognostic significance of HPV-related OPSCC in Thai patients. METHODS: The study included patients with OPSCC who were treated at Songklanagarind Hospital (Songkhla, Southern Thailand) from 2009 to 2020. HPV status was screened by p16 expression using immunohistochemistry and confirmed by real-time polymerase chain reaction. Cox regression was used to determine prognostic significance. RESULTS: The overall proportion of HPV+ OPSCC was 15.3% (95% confidence interval [CI]: 12.1-18.5) with a slightly increased proportion from 10.6% in 2009-2010 to 16.5% (2019-2020) (P for trend = 0.166). Among the HPV+ cases, HPV16 was detected in 65.3%, HPV18 in 34.7%, and other high-risk HPV types in 24%. Patients with P16+ or HPV+ OPSCC had significantly better overall survival (hazard ratio [HR]: 0.63, 95% CI: 0.45-0.90 and HR: 0.63, 95% CI: 0.45-0.88, respectively). CONCLUSION: Thai patients in the southern region have a low proportion of HPV-related OPSCC with an increasing trend. Both P16 expression and HPV DNA status are strong independent prognostic factors of OPSCC.

Oral and oropharyngeal cancer screening and tobacco cessation discussions, NHANES 2011-2018.

OBJECTIVE: Oral cavity and oropharyngeal cancer (OOPC) is a devastating disease often caught in late stages. People who use tobacco are at higher risk of OOPC. Tobacco cessation discussions and OOPC screenings are important factors in decreasing the risk of OOPC or its late stage diagnosis. As research on sex differences has been increasing-from research on biomedical to psychological and sociological determinants-there is a potential difference, by sex, as to whom is more likely to have a tobacco cessation discussion and OOPC screening. The objective of this study is to determine if there is an association of sex with tobacco cessation discussions and OOPC screenings conducted by dental healthcare professionals among participants who currently use tobacco. METHOD: Data from 8 years of the National Health and Nutrition Examination Survey (2011-2018) were merged. Data from participants, ages 30 years and above, who self-reported current use of tobacco, a dental visit within the previous year and responsed to questions about oral cancer screening were analysed for frequency determination and logistic regression analysis. Having the combination of neither OOPC screening nor discussion about the benefits of not using tobacco was the outcome in the analysis. RESULTS: There were 22.1% who had an OOPC screening by a dental professional within the previous year. Of the 41% who reported having had a conversation with a dental professional within the previous year about the benefits of tobacco cessation, 9.8% reported having both the conversation and OOPC screening. Males were less likely than females to have the combination of neither OOPC screening nor advice about tobacco cessation than females (adjusted odds ratio: 0.74; 95%CI: 0.57, 0.96). CONCLUSION: There is an increased need for OOPC screening and the discussion of tobacco use by dental professionals among their patients who use tobacco, particularly for female patients.