[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.

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.

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.

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.

Occupational variation in incidence of oropharyngeal cancer in the Nordic countries.

PURPOSE: Evaluate the occupational variation in incidence of oropharyngeal cancer (OPC). METHODS: We calculated standardized incidence ratios (SIRs) of OPC in occupational categories in the Nordic countries relative to the entire national populations. The data covered 6155 OPC cases. RESULTS: Among men high risk of OPC was observed, among else, in waiters (SIR 6.28, 95% CI 4.68-8.26), beverage workers (SIR 3.00, 95% CI 1.72-4.88), and artistic workers (SIR 2.97, 95% CI 2.31-3.76). Among women high risk of OPC was observed in waiters (SIR 2.02, 95% CI 1.41-2.81) and packers (SIR 1.73, 95% CI 1.07-2.64). The lowest SIRs were observed in female gardeners (SIR 0.27, 95% CI 0.12-0.51) and male farmers (SIR 0.30, 95% CI 0.25-0.35). CONCLUSION: The 20-fold variation in incidence of OPC between occupations needs further investigation in studies with detailed information on occupational and non-occupational risk factors.

Increasing Patients With HPV-positive Oropharyngeal Squamous Cell Carcinoma and its Oncologic Outcomes in the Rural Region in Northern Japan.

BACKGROUND/AIM: Despite the global rise in the incidence of human papillomavirus (HPV)-positive oropharyngeal carcinoma (OPC) in recent years, its prevalence and oncological outcomes in patients living in rural areas of Northern Japan has not been explored and should be investigated. PATIENTS AND METHODS: A total of 105 patients with oropharyngeal squamous cell carcinoma who underwent HPV screening and received first-line treatment were included in this study. The annual changes in the number of patients, survival rates, and clinical factors affecting prognosis were examined. RESULTS: The HPV-positive rate in patients with OPC was low, with the lowest rate of 10.0% in 2013 and the highest rate of 46.7% in 2020. The number of HPV-negative cases remained almost unchanged, whereas the overall number of cases increased with the increasing number of HPV-positive cases. Additionally, HPV-positive cases exhibited a fairly good prognosis. CONCLUSION: The number of OPC cases increased not only in urban areas, but also in rural areas. HPV-positive cases had better outcomes than HPV-negative cases.

Contribution of public oral pathology services to the diagnosis of oral and oropharyngeal cancer in Brazil.

This study aimed to evaluate the contribution of oral and maxillofacial pathology laboratories (OMPLs) in Brazilian public universities to the diagnosis of lip, oral cavity, and oropharyngeal squamous cell carcinoma (SCC). A cross-sectional study was performed using biopsy records from a consortium of sixteen public OMPLs from all regions of Brazil (North, Northeast, Central-West, Southeast, and South). Clinical and demographic data of patients diagnosed with lip, oral cavity, and oropharyngeal SCC between 2010 and 2019 were collected from the patients' histopathological records. Of the 120,010 oral and maxillofacial biopsies (2010-2019), 6.9% (8,321 cases) were diagnosed as lip (0.8%, 951 cases), oral cavity (4.9%, 5,971 cases), and oropharyngeal (1.2%, 1,399 cases) SCCs. Most cases were from Brazil's Southeast (64.5%), where six of the OMPLs analyzed are located. The predominant profile of patients with lip and oral cavity SCC was Caucasian men, with a mean age over 60 years, low schooling level, and a previous history of heavy tobacco consumption. In the oropharyngeal group, the majority were non-Caucasian men, with a mean age under 60 years, had a low education level, and were former/current tobacco and alcohol users. According to data from the Brazilian National Cancer Institute, approximately 9.9% of the total lip, oral cavity, and oropharyngeal SCCs reported over the last decade in Brazil may have been diagnosed at the OMPLs included in the current study. Therefore, this data confirms the contribution of public OMPLs with respect to the important diagnostic support they provide to the oral healthcare services extended by the Brazilian Public Health System.

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.

Occupational Etiology of Oropharyngeal Cancer: A Literature Review.

While abundant evidence exists linking alcohol, tobacco, and HPV infection to a carcinogenic impact on the oropharynx, the contribution of inhalational workplace hazards remains ill-defined. We aim to determine whether the literature reveals occupational environments at a higher-than-average risk of developing oropharyngeal cancer (OPC) and summarize the available data. To identify studies assessing the relationship between occupational exposure and risk of OPC, a search of the literature through the PubMed-NCBI database was carried out and, ultimately, 15 original articles meeting eligibility criteria were selected. Only original articles in English focusing on the association between occupational exposure and risk or death of specifically OPC were included. The available data are supportive of a potentially increased risk of OPC in waiters, cooks and stewards, artistic workers, poultry and meat workers, mechanics, and World Trade Center responders exposed to dust. However, the available literature on occupation-related OPC is limited. To identify occupational categories at risk, large cohorts with long follow-ups are needed. Identification of causal associations with occupation-related factors would require dose-response analyses adequately adjusted for confounders.

Latin American and the Caribbean Code Against Cancer 1st edition: Infections and cancer.

About 13% of all cancers around the world are associated with infectious agents, particularly in low-resource settings. The main infectious agents associated with cancer are Helicobacter pylori (H. pylori), that causes gastric cancer, human papillomavirus (HPV) that causes cervical, vulvar, vaginal, penile, anal, and oropharyngeal cancer, hepatitis B and C viruses that cause liver cancer, and human immunodeficiency virus (HIV), associated with cancers of the cervix, Kaposi sarcoma (KS) and non-Hodgkin´s lymphoma. In Latin America and the Caribbean (LAC), about 150,000 cancer cases are caused annually by infections. The LAC Cancer Code Against Cancer consists of a set of 17 evidence-based and individual-level cancer prevention recommendations targeted to the general population, suited to the epidemiological, socioeconomic, and cultural conditions of the region, and tailored to the availability and accessibility of health-care systems. The recommendations with respect to infection-driven malignancies include testing and treating for H. pylori in the context of specific public health programs, vaccination against HPV and Hepatitis B Virus (HBV) and detection and treatment of chronic infections with HBV, Hepatitis C virus (HCV) and HIV, in addition to the promotion of safe sex and use of condoms to prevent sexually transmitted infections (STI). Countries, policy makers, health care systems and individuals should consider the adoption of these recommendations to help reduce the incidence and mortality of infection-related cancers in LAC, to improve quality of life of individuals and reduce the costs of cancer care in the region.

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

Importance: 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. Objective: To assess oral HPV prevalence and factors associated with HR and low-risk infection in a general US population. Design, Setting, and Participants: 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. Exposure: 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. Main Outcome: Oral HPV prevalence. Results: 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). Conclusions and Relevance: 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.

The relation between human papillomavirus (HPV) and oropharyngeal cancer: a review.

Oropharyngeal squamous cell carcinomas (OPSCC) represent a major public health challenge. In 2020, the international agency for research on cancer (IARC) recorded 98,421 cases of OPSCC worldwide. Over the past decade, the epidemiological profile of patients with OPSCC has shifted, mainly due to a change in etiological factors. Previously, alcohol and tobacco were considered the primary contributors, but the human papillomavirus (HPV) is now recognized as the leading cause of these tumors. This study aimed to conduct a literature review on the relationship between OPSCC and HPV for the general practitioner. The review examined the primary clinical differences between HPV+ and HPV- OPSCC, their prognosis and treatment. In addition, the various HPV diagnostic methods were analyzed. Although there is a vast amount of literature on HPV, this review is unique in its ability to present the key information in an organized and accessible way and enables healthcare professionals to gain a better understanding of the relationship between HPV and oropharyngeal cancer. This, in turn, can contribute to the prevention of various cancers caused by the HPV virus, including oropharyngeal cancer.

Incidence, trends, and survival of oropharyngeal squamous cell cancer in Aotearoa New Zealand, 2006-2020.

BACKGROUND: An increasing trend of oropharyngeal cancer (OPC) has been reported in several countries with different demographic characteristics, and often attributed to increases in human papillomavirus (HPV) infection. The survival of patients with OPC has steadily improved, especially for those with positive HPV status. This study assessed the incidence, trends, and survival of OPC in Aotearoa New Zealand (NZ) by age at diagnosis, sex and ethnicity. METHODS: The study included all 2109 patients resident in NZ with a primary diagnosis of oropharyngeal squamous cell carcinoma from 2006 to 2020, identified from the National Cancer Registry. We assessed age-standardised incidence rate (ASR), annual percent change (APC) and overall and relative survival rates. RESULTS: The average annual incidence of OPC was 2.2 per 100,000 population. There was a steady increase of 4.9% per year over 15 years. Although the incidence rates were higher in males over the study period, the overall rate of increase was similar in males (4.9%) and in females (4.3%). The incidence was highest in the 50-69-year group (8.8/100,000 population). This age group had an incidence that increased by 7.5% per year to 2018, and then declined. The main increase in rates was seen between the birth cohort of 1946-50 and that of 1956-60. The increase in incidence was seen in Maori and Pakeha/European populations, but no increase was seen in Pacific or Asian populations. The 5-year overall relative survival rate improved from 69% in 2006-13 to 78% in 2014-20. Survival rates were lower in older patients, females, and Maori patients. CONCLUSION: This study confirmed a substantial increase in OPC incidence in NZ, with some evidence to suggest a recent slowing in this increase. Maori and Pakeha/European had the highest incidence, while Pacific and Asian populations showed the lowest rates and no increase over the study period. Survival rates have improved over time, but remained lower in some demographic groups.