Clinical prognostic factors to guide treatment strategy for HPV­positive oropharyngeal cancer using treatment outcomes of induction chemotherapy: A real­world experience.

The role of induction chemotherapy (IC) in locally advanced oropharyngeal cancer (OPC) remains debatable, and suitable candidates for de-escalation treatment in these patients have not been fully identified. Therefore, the present study aimed to identify high-risk candidates for human papillomavirus (HPV)-positive OPC by analyzing patients who underwent IC followed by chemoradiotherapy (CRT) to guide optimal treatment strategies. Patients diagnosed with stage III-IVA OPC and treated with a minimum of two cycles of IC followed by CRT, between 2004 and 2020, were retrospectively reviewed. All the patients were restaged according to the American Joint Committee on Cancer, 8th edition. The overall response rate and survival outcomes associated with clinical factors based on HPV status were analyzed using univariate and multivariate analyses. The present study analyzed 105 patients with a median age of 60 years (range, 40-76 years). Among 105 patients, 40 (38.1%) were HPV-negative and 65 (61.9%) HPV-positive. In all patients, survival outcomes were notably poorer in patients aged ≥60 years (P=0.006) and those who did not achieve complete response post-CRT (P<0.001), irrespective of the HPV status. The median relative dose intensity of IC was ≥80%, indicating adequate treatment, regardless of age. In contrast to patients with HPV-negative OPC, age ≥60 years (P=0.011) and T4 stage (P=0.019) emerged as substantial poor prognostic factors for survival outcomes in patients with HPV-positive OPC. Patients with HPV-positive OPC were categorized into three groups based on the number of clinical factors at diagnosis (such as age and T4 stage). The progression-free and overall survival showed significant stratification across each group as the number of high-risk factors increased despite IC and CRT. The findings indicated that patients with these high-risk factors require a cautious therapeutic strategy even when they are diagnosed with HPV-positive OPC, and the role of combined modality, including IC, will need to be investigated in a randomized trial to be routinely incorporated into clinical practice.

STEPS (Study To Examine Parent, Patient/Dental Provider Systems) to Prevent Human Papillomavirus (HPV)-Related Cancers: A Piloted Dental Patient and Provider Evaluation of Current and Future HPV Education.

Oropharyngeal human papillomavirus (HPV) cancers are prevalent, but HPV education in dental clinics is uncommon. The purpose of this study was to evaluate dental provider and patient knowledge from, attitudes towards, and preferences for HPV education, then assess perceptions of existing HPV educational materials for use at dental visits. Appalachian Ohio dental patients (n = 13) and general/pediatric dental providers (n = 10) completed an initial, close-ended survey on current HPV knowledge and HPV educational attitudes, participation, and resource preferences. Select individuals reviewed existing HPV educational videos and toolkits via virtual focus groups (n = 9) or independent review surveys (n = 6). Using a discussion guide, participants responded to overall, visual, auditory, and content satisfaction statements, orally (focus groups) or with Likert scales (independent reviews). Surveys were summarized with frequencies/percentages; transcripts were qualitatively coded to identify potential material modifications. Dental providers and patients were more comfortable with HPV and oral cancer education (87% and 96%, respectively) and screening (96%) than with HPV vaccine education (74%) and referrals (61%) during dental visits. Providers were neither sharing HPV educational materials (80%) nor initiating educational conversations with dental patients (100%). The American Cancer Society videos and the "Team Maureen" toolkit were the most liked resources (i.e., fewer negative/disagree statements) by all participant groups. Findings indicate that future dental HPV educational efforts should be informed by currently available materials. Additional interventions are needed to promote dental provider discussions and sharing of educational materials with patients to increase education and promotion of the HPV vaccine and reduce oropharyngeal cancers.

Novel gene fusions in human oropharyngeal carcinoma.

Few reports have analyzed the fusion genes involved in carcinogenesis in the oropharynx, where the incidence of human papillomavirus-associated tumors is relatively low. The aim of this study was to identify novel driver fusion genes in patients with oropharyngeal cancer. The study enrolled fifty-seven patients who were diagnosed with oropharyngeal carcinoma. RNA sequencing data from fresh-frozen specimens were used to identify candidate fusion genes via the JAFFA, arriba, and STAR-Fusion pipelines. Candidate fusion genes were confirmed by direct sequencing. The expression level of a candidate fusion gene was compared to that of tumors without fusion genes. Finally, filtering was performed for driver genes using the annoFuse pipeline. In addition, the VIRTUS pipeline was used to analyze the presence of human papillomavirus in the tumors. We identified 5 (8.8 %) novel potential driver in-frame fusion genes, MKNK2::MOB3A, ICMT::RPS6KA3, ATP1B3::GRK7, CSNK2A1::KIF16B, and FGFR3::MAEA, and 1 (1.8 %) known in-frame fusion gene, FGFR3::TACC3, in 57 patients with pharyngeal carcinoma. Our results suggest that sporadic fusion genes may contribute to tumorigenesis in oropharyngeal carcinomas.

Concentration of High-Cost Head and Neck Cancer Surgical Patients.

OBJECTIVE: Health care costs are disproportionately concentrated among a small number of patients. We sought to identify variables associated with high-cost patients and high hospital concentration of high-cost patients and to examine associations with short-term outcomes in head and neck cancer (HNCA) surgery. STUDY DESIGN: The Nationwide Inpatient Sample was used to identify 170,577 patients who underwent HNCA surgery in 2001-2011. High-cost patients were defined as patients whose costs of care were in the top decile, and high-concentration hospitals were defined as those whose percentage of high-cost patients was in the top decile. METHODS: Multivariable regression was used to evaluate associations between cost and patient and hospital variables, postoperative complications, and in-hospital mortality. RESULTS: Costs associated with high-cost patients were 4.47-fold greater than the remaining 90% of patients. High-concentration hospitals treated 36% of all high-cost patients. High-cost patients were more likely to be non-white (OR = 2.08 [1.45-2.97]), have oral cavity cancer (OR = 1.21 [1.05-1.39]), advanced comorbidity (OR = 1.53 [1.31-1.77]), Medicaid (OR = 1.93 [1.62-2.31]) or self-pay payor status (OR = 1.72 [1.38-2.14]), income>50th percentile (OR = 1.25 [1.05-1.51]), undergo major procedures (OR = 3.52 [3.07-4.05]) and have non-routine discharge (OR = 7.50 [6.01-9.35]). High-concentration hospitals were more likely to be teaching hospitals (OR = 3.14 [1.64-6.05]) and less likely to be urban (OR = 0.20 [0.04-0.93]). After controlling for all other variables, high-cost patients were associated with an increased odds of mortality (OR = 8.00 [5.89-10.85]) and postoperative complications (OR = 5.88 [5.18-6.68]). High-concentration hospitals were associated with an increased odds of postoperative complications (OR = 1.31 [1.08-1.61]) but were not associated with increased mortality (OR = 0.98 [0.67-1.44]). CONCLUSIONS: High-cost HNCA surgical patients are associated with increased postoperative morbidity and mortality, and are disproportionately concentrated at teaching hospitals. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Los Angeles County dentists' opinions on discussing human papilloma virus-related oral health issues and recommending vaccine to patients.

Dentists are well-positioned to discuss oral health issues related to Human Papillomavirus (HPV) and recommend the HPV vaccine to their patients, mainly because the HPV virus causes oropharyngeal cancers.. We assessed Los Angeles (LA) County dentists' opinions on discussing HPV-related oral health issues and recommending the HPV vaccine to their patients. We tested if opinions differed between dentists whose primary patient population was only adults versus children and adults. We mailed a 19-item survey to 2000 randomly sampled LA County dentists for this cross-sectional study. The primary outcome variable was a summary opinion score of 7 opinion statements. We ran descriptive, bivariate comparisons and adjusted linear regression models. Overall, 261 dentists completed the survey. A majority (58.5%) worried they would lose patients if they recommended the vaccine; 49% thought dentists were not appropriate to educate, counsel, or advise on HPV-related issues; 42% were concerned about the safety of the vaccine; and 40% did not feel comfortable recommending the vaccine. The mean summary opinion score was 21.4 ± 5.4 for the total sample. Regression analysis showed no differences in opinions between dentists whose primary patient population was only adults versus children and adults (Coefficient = 0.146, p = 0.83). Overall, the responding dentists were not very favorable about discussing oral health-related HPV issues and recommending the HPV vaccine to their patients. Additionally, the overall opinions were similar between dentists whose primary patient population was only adults versus children and adults.

Utility of TTMV-HPV DNA in resolving indeterminate findings during oropharyngeal cancer surveillance.

OBJECTIVES: Clinical and imaging examinations frequently have indeterminate results during cancer surveillance, which can lead to overtreatment and cause psychological and financial harm to the patient. This study addresses the critical need to enhance diagnostic precision and decision-making in the management of HPV-associated oropharyngeal cancer. This study evaluated the utility of tumor tissue-modified viral (TTMV)-HPV DNA to resolve indeterminate disease status following definitive treatment for HPV-associated oropharyngeal cancer. MATERIALS AND METHODS: In this retrospective cohort, patients treated for HPV-associated oropharyngeal cancer at eight U.S. institutions and who received one or more TTMV-HPV DNA tests during post-treatment surveillance between February 2020 and January 2022 were included. RESULTS: Among 543 patients, 210 patients (38.7%; 210/543) experienced one or more clinically indeterminate findings (CIFs) during surveillance, with 503 CIFs recorded. Of those patients with an "indeterminate" disease status at a point during surveillance, 79 were associated with contemporaneous TTMV-HPV DNA testing. TTMV-HPV DNA testing demonstrated high accuracy (97.5%; 77/79) in correctly determining recurrence status. Patients whose disease status was "indeterminate" at the time of a positive TTMV-HPV DNA test were clinically confirmed to recur faster than those whose disease status was "no evidence of disease." Only 3% of patients (17/543) experienced indeterminate TTMV-HPV DNA tests during surveillance. Discordance between TTMV-HPV DNA tests and clinical results was minimal, with only 0.6% (3/543) of patients showing positive tests without recurrence. CONCLUSION: Our findings support the utility of circulating TTMV-HPV DNA in resolving indeterminate disease status and informing the subsequent clinical course.

Oropharyngeal cancer and human papillomavirus: a visualization based on bibliometric analysis and topic modeling.

Objectives: The incidence of oropharyngeal cancer (OPC) is increasing. This study used bibliometric analysis and topic modeling to explore the research trends and advancements in this disease over the past 10 years, providing valuable insights to guide future investigations. Methods: 7,355 English articles from 2013 to 2022 were retrieved from the Web of Science Core Collection for bibliometric analysis. Topic modeling was applied to 1,681 articles from high-impact journals, followed by an assessment of topic significance ranking (TSR). Medical Subject Headings (MeSH) terms were extracted using R and Python, followed by an analysis of the terms associated with each topic and on an annual basis. Additionally, genes were extracted and the number of genes appearing each year and the newly emerged genes were counted. Results: The bibliometric analysis suggested that the United States and several European countries hold pivotal positions in research. Current research is focused on refining treatments, staging and stratification. Topic modeling revealed 12 topics, emphasizing human papillomavirus (HPV) and side effect reduction. MeSH analysis revealed a growing emphasis on prognosis and quality of life. No new MeSH terms emerged after 2018, suggesting that the existing terms have covered most of the core concepts within the field of oropharyngeal cancers. Gene analysis identified TP53 and EGFR as the most extensively studied genes, with no novel genes discovered after 2019. However, CD69 and CXCL9 emerged as new genes of interest in 2019, reflecting recent research trends and directions. Conclusion: HPV-positive oropharyngeal cancer research, particularly treatment de-escalation, has gained significant attention. However, there are still challenges in diagnosis and treatment that need to be addressed. In the future, more research will focus on this issue, indicating that this field still holds potential as a research hotspot.

Current Status and Future Directions of Proton Therapy for Head and Neck Carcinoma.

The growing interest in proton therapy (PT) in recent decades is justified by the evidence that protons dose distribution allows maximal dose release at the tumor depth followed by sharp distal dose fall-off. But, in the holistic management of head and neck cancer (HNC), limiting the potential of PT to a mere dosimetric advantage appears reductive. Indeed, the precise targeting of PT may help evaluate the effectiveness of de-escalation strategies, especially for patients with human papillomavirus associated-oropharyngeal cancer (OPC) and nasopharyngeal cancer (NPC). Furthermore, PT could have potentially greater immunogenic effects than conventional photon therapy, possibly enhancing both the radiotherapy (RT) capability to activate anti-tumor immune response and the effectiveness of immunotherapy drugs. Based on these premises, the aim of the present paper is to conduct a narrative review reporting the safety and efficacy of PT compared to photon RT focusing on NPC and OPC. We also provide a snapshot of ongoing clinical trials comparing PT with photon RT for these two clinical scenarios. Finally, we discuss new insights that may further develop clinical research on PT for HNC.

Human papillomavirus-driven head and neck cancers in Japan during 2008-2009 and 2018-2019: The BROADEN study.

There is limited understanding of epidemiology and time trends of human papilloma virus (HPV)-driven head and neck cancers (HNC) in Japan, especially outside of the oropharynx. To assess HPV-driven HNC, a non-interventional study (BROADEN) of HNC patients diagnosed in 2008-2009 and 2018-2019 was conducted in Japan. Adult patients with oropharyngeal, nasopharyngeal, laryngeal, hypopharyngeal or oral cavity cancers were included in this study. HPV was centrally tested using p16INK4a immunohistochemistry, HPV-DNA PCR and HPV E6*I mRNA. HPV attributability required positivity in at least two tests (p16INK4a immunohistochemistry, HPV-DNA PCR, HPV E6*I mRNA) in the oropharynx, and HPV-DNA and HPV E6*I mRNA positivity for non-oropharynx sites. Nineteen hospitals included a total of 1108 patients, of whom 981 had valid samples. Men accounted for 82% of HNC diagnoses. Patients in the earlier cohort were younger and included a higher percentage of smokers. There was an increasing trend of HPV-driven oropharyngeal cancer over the last decade, from 44.2% to 51.7%. HPV attribution in nasopharyngeal cancers was 3.2% in 2008-2009 and 7.5% in 2018-2019; and 4.4% and 0% for larynx respectively. In total, 95.2% of HPV-driven HNC were attributed to HPV genotypes included in the 9-valent HPV vaccine being HPV16 the most prominent genotype. These results suggest that an epidemiologic shift is happening in Japan, with a decrease in smoking and alcohol use and an increase in HPV-driven HNC. The increasing trend of HPV-driven HNC in Japan highlights the need for preventive strategies to mitigate the rise of HPV-driven HNC.

Comparison of Doses to Parotid, Temporomandibular Joint, and Pharyngeal Constrictor Muscles Using Different Techniques in Radiotherapy for Oropharyngeal Cancer.

OBJECTIVE: The purpose of this research was to compare two treatment techniques for oropharyngeal cancers: conventional linac-based static intensity-modulated radiotherapy (sIMRT) and helical tomotherapy (HT). The study examined several parameters, including target coverage, organs at risk, integral dose, and beam on time. Additionally, the study evaluated the doses to the parotid, temporomandibular joint, and pharyngeal constrictor muscles, which are important for swallowing. METHOD: The present study retrospectively analyzed the data of 13 patients with oropharyngeal cancer who underwent radiotherapy between 2019 and 2021. The treatment plans for each patient were regenerated using both sIMRT and HT treatment planning systems with the sequential boost method. The techniques were evaluated and compared based on dose-volume histogram, homogeneity index, and conformity index parameters. The target coverage and organs at risk were statistically compared for two techniques. Additionally, the doses received by the healthy tissue volume were obtained for integral dose evaluation. The beam on time for each technique was assessed. RESULTS: When considering planning target volume evaluation, there was no difference in Dmeans between the two techniques and sIMRT demonstrated higher D2% values compared to the HT. The HT technique had better results for all organs at risk, such as the parotid, temporomandibular joint, and pharyngeal constrictor muscle. As for integral dose, it has been shown that the sIMRT technique provides better protection compared to HT. In addition, the beam on time was also longer with the HT technique. CONCLUSION: Both techniques may provide optimal target coverage for patients with oropharyngeal cancer. HT conferred notable advantages, especially with regard to critical structures implicated in swallowing, such as the parotid, temporomandibular joint, and pharyngeal constrictor muscle, in comparison to sIMRT.

Computer Vision Foundation Models in Endoscopy: Proof of Concept in Oropharyngeal Cancer.

OBJECTIVES: To evaluate the performance of vision transformer-derived image embeddings for distinguishing between normal and neoplastic tissues in the oropharynx and to investigate the potential of computer vision (CV) foundation models in medical imaging. METHODS: Computational study using endoscopic frames with a focus on the application of a self-supervised vision transformer model (DINOv2) for tissue classification. High-definition endoscopic images were used to extract image patches that were then normalized and processed using the DINOv2 model to obtain embeddings. These embeddings served as input for a standard support vector machine (SVM) to classify the tissues as neoplastic or normal. The model's discriminative performance was validated using an 80-20 train-validation split. RESULTS: From 38 endoscopic NBI videos, 327 image patches were analyzed. The classification results in the validation cohort demonstrated high accuracy (92%) and precision (89%), with a perfect recall (100%) and an F1-score of 94%. The receiver operating characteristic (ROC) curve yielded an area under the curve (AUC) of 0.96. CONCLUSION: The use of large vision model-derived embeddings effectively differentiated between neoplastic and normal oropharyngeal tissues. This study supports the feasibility of employing CV foundation models like DINOv2 in the endoscopic evaluation of mucosal lesions, potentially augmenting diagnostic precision in Otorhinolaryngology. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Development and external validation of a head and neck cancer risk prediction model.

BACKGROUND: Head and neck cancer (HNC) incidence is on the rise, often diagnosed at late stage and associated with poor prognoses. Risk prediction tools have a potential role in prevention and early detection. METHODS: The IARC-ARCAGE European case-control study was used as the model development dataset. A clinical HNC risk prediction model using behavioral and demographic predictors was developed via multivariable logistic regression analyses. The model was then externally validated in the UK Biobank cohort. Model performance was tested using discrimination and calibration metrics. RESULTS: 1926 HNC cases and 2043 controls were used for the development of the model. The development dataset model including sociodemographic, smoking, and alcohol variables had moderate discrimination, with an area under curve (AUC) value of 0.75 (95% CI, 0.74-0.77); the calibration slope (0.75) and tests were suggestive of good calibration. 384 616 UK Biobank participants (with 1177 HNC cases) were available for external validation of the model. Upon external validation, the model had an AUC of 0.62 (95% CI, 0.61-0.64). CONCLUSION: We developed and externally validated a HNC risk prediction model using the ARCAGE and UK Biobank studies, respectively. This model had moderate performance in the development population and acceptable performance in the validation dataset. Demographics and risk behaviors are strong predictors of HNC, and this model may be a helpful tool in primary dental care settings to promote prevention and determine recall intervals for dental examination. Future addition of HPV serology or genetic factors could further enhance individual risk prediction.

Prognostic role of lymph node micrometastasis in oral and oropharyngeal cancer: A systematic review.

BACKGROUND: An estimated 20% of patients with oral and oropharyngeal squamous cell carcinoma (OOSCC) have micrometastases (Mi) or isolated tumor cells (ITC) in the cervical lymph nodes that evade detection by standard histological evaluation of lymph node sections. Lymph node Mi and ITC could be one reason for regional recurrence after neck dissection. The aim of this study was to review the existing data regarding the impact of Mi on the survival of patients with OOSCC. METHODS: PubMed and the Cochrane Library were searched for articles reporting the impact of Mi and ITC on patient survival. Two authors independently assessed the methodological quality of retrieved studies using the Downs and Black index. Data were also extracted on study type, number of included patients, mode of histological analysis, statistical analysis, and prognostic impact. RESULTS: Sixteen articles with a total of 2064 patients were included in the review. Among the 16 included studies, eight revealed a statistically significant impact of Mi on at least one endpoint in the Kaplan-Meier and/or multivariate analysis. Three studies regarded Mi as Ma, while five studies found no impact of Mi on survival. Only one study demonstrated an impact of ITC on patient's prognosis in the univariate but not in the multivariate analysis. CONCLUSION: The majority of cases included in the review were patients with oral cancer. The findings provide low-certainty evidence that Mi negatively impacts survival. Data on ITC were scarcer, so no conclusions can be drawn about their effect on survival. The lower threshold to discriminate between Mi and ITC should be defined for OOSCC since the existing thresholds are based on data from different tumors. The histological, immunohistological, and anatomical characteristics of Mi and ITC in OOSCC as well as the effect of radiotherapy on Mi should be further investigated separately for oral and oropharyngeal carcinomas.

PET/CT based transformer model for multi-outcome prediction in oropharyngeal cancer.

BACKGROUND AND PURPOSE: To optimize our previously proposed TransRP, a model integrating CNN (convolutional neural network) and ViT (Vision Transformer) designed for recurrence-free survival prediction in oropharyngeal cancer and to extend its application to the prediction of multiple clinical outcomes, including locoregional control (LRC), Distant metastasis-free survival (DMFS) and overall survival (OS). MATERIALS AND METHODS: Data was collected from 400 patients (300 for training and 100 for testing) diagnosed with oropharyngeal squamous cell carcinoma (OPSCC) who underwent (chemo)radiotherapy at University Medical Center Groningen. Each patient's data comprised pre-treatment PET/CT scans, clinical parameters, and clinical outcome endpoints, namely LRC, DMFS and OS. The prediction performance of TransRP was compared with CNNs when inputting image data only. Additionally, three distinct methods (m1-3) of incorporating clinical predictors into TransRP training and one method (m4) that uses TransRP prediction as one parameter in a clinical Cox model were compared. RESULTS: TransRP achieved higher test C-index values of 0.61, 0.84 and 0.70 than CNNs for LRC, DMFS and OS, respectively. Furthermore, when incorporating TransRP's prediction into a clinical Cox model (m4), a higher C-index of 0.77 for OS was obtained. Compared with a clinical routine risk stratification model of OS, our model, using clinical variables, radiomics and TransRP prediction as predictors, achieved larger separations of survival curves between low, intermediate and high risk groups. CONCLUSION: TransRP outperformed CNN models for all endpoints. Combining clinical data and TransRP prediction in a Cox model achieved better OS prediction.

Outcomes for potentially Resectable patients undergoing primary chemoradiation treatment for T1-T2 HPV Negative oropharyngeal squamous cell carcinoma.

BACKGROUND: Transoral surgical resectability (TOS) is a prognostic factor for patients with HPV+ T1-2 oropharyngeal squamous cell carcinoma (OPSCC) disease undergoing radiotherapy (RT), but it is unclear whether this holds for HPV-negative (HPV-) patients. We aimed to compare outcomes of potential TOS-candidates vs. non-TOS candidates, among patients who underwent RT/CRT for early T-stage HPV- OPSCC. METHODS: For patients treated with RT/CRT for early T-stage HPV-negative OPSCC between 2014 and 2021, pretreatment imaging was reviewed by four head-and-neck surgeons, masked to clinical outcomes, to assess primary-site suitability for TOS. Extracapsular extension (ECE) was assessed by a head-and-neck neuroradiologist. We compared outcomes based on surgical resectability relating to: (1) the primary site tumor alone, and (2) the primary site plus the absence/presence of ECE (overall assessment). Kaplan-Meier curves for overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS) were compared using the log-rank test. RESULTS: Seventy patients were included in the analysis. The primary site was TOS-favorable in 46/70 (66%). Based on the overall assessment, 41/70 (58.6%) were TOS-favorable. The 3-year OS, DSS and PFS for primary site TOS-favorable versus unfavorable were OS: 76.9% versus 37.4%; DSS: 78.1% versus 46.2%, PFS: 69.9% versus 41.3%, (log-rank test = 0.01, 0.03, 0.04; respectively). Additionally, patients with an overall assessment of TOS favorability demonstrated better survival outcomes compared with TOS-unfavorable patients (OS: 77.3% vs. 46.2%; DSS: 78.2% vs. 56.5%, PFS: 72.3% vs. 42.1%, log-rank test = 0.01, 0.04, 0.01; respectively). CONCLUSION: Patients with TOS-favorable HPV-negative early T-stage OPSCC have superior survival outcomes than TOS-unfavorable patients.

Indications for oropharyngeal biopsy in head and neck squamous cell carcinoma of unknown primary: A systematic review (HNSCCUP).

INTRODUCTION: Patients presenting with head and neck squamous cell carcinoma of unknown primary (HNSCCUP) remain challenging clinical scenarios as large variation exists in practices used to locate the primary. OBJECTIVE: The objective of this systematic review is to review of the literature and offer recommendations for oropharyngeal biopsies in HNSCCUP. METHOD: Pubmed, Medline and Embase were searched to identify studies from inception to October 2021. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. RESULTS: A total of 483 articles were included and screened, 41 studies met the inclusion criteria, including over 3400 patients from the original articles (122 of these patients were reported on in two sequential articles by a single author - table 1) and 4 large metaanalyses including 1852 patients. The primary site identification rate following random biopsies or deep tissue biopsies is less than 5% in most studies. The mean detection rate following ipsilateral tonsillectomy is 34%; two pooled analyses indicate that the mean detection rate following tongue base mucosectomy is 64%, with this figure rising when the tonsils are negative. CONCLUSIONS: High level evidence is lacking, with heterogeneity in the reported studies. Published meta-analyses are based on retrospective data. There is little evidence supporting the practice of random/non-directed oropharyngeal biopsies. Available evidence supports palatine tonsillectomy and tongue base mucosectomy compared to deep tissue biopsies.

Human papillomavirus circulating tumor DNA assays as a mechanism for head and neck cancer equity in rural regions of the United States.

The rates of human papillomavirus-positive oropharyngeal cancer (HPV-OPC) are rising worldwide and in the United States, particularly in rural regions including Appalachia. Rural areas face unique health challenges resulting in higher cancer incidence and mortality rates, and this includes HPV-OPC. The recent advent of highly sensitive liquid biopsies for the non-invasive detection of HPV-OPC recurrence (circulating tumor HPV DNA, HPV ctDNA) has been swiftly adopted as part of surveillance paradigms. Though knowledge gaps persist regarding its use and clinical trials are ongoing, the ease of collection and cost-effectiveness of HPV ctDNA make it more accessible for HPV-OPC survivors than usual surveillance methods of frequent exams and imaging. Herein, we discuss how implementing HPV ctDNA assays in rural regions of the United States provide one poignant example of how liquid biopsies can improve cancer care equity.

Case-finding for HPV vaccination eligibility within a dental office with concurrent development of a dialogue tool.

Background: Human papillomavirus (HPV) immunization can prevent cancers, but uptake has been incomplete (and worse with the COVID-19 pandemic). Dental clinicians already screen for oral cancers, many of which are caused by HPV, and could identify vaccination candidates, but this requires a case-finding strategy. Objective: The purpose of this study was (1) to develop and test a case-finding approach to identify patients who were candidates for HPV vaccinations, (2) to test an HPV vaccination intervention by dental professionals on vaccination uptake. Methods: Design: Prospective, non-randomized feasibility case finding study with a 4-week enrollment period and a 6 week follow up period in general dental offices.Setting: Two general and non-commercial dentistry offices in Edmonton, Alberta Canada.Subjects: Consecutive scheduled (non-emergent) patients who met the Health Canada criteria for HPV vaccination: immunocompetent males and females aged 9-45 years and those who are immunocompromised. Consent for the discussion was obtained from each subject or parent.Intervention: Scheduled dental patients meeting the inclusion criteria were flagged by a research assistant who reviewed the appointment schedule each week for 4 weeks. For these subjects, dental clinicians (dentists and dental hygienists) used our Dental Dialogue Tool to discuss HPV vaccination and answer questions. Participating patients who consented to receive the HPV vaccine were given a prescription by the attending dentist and were directed to follow-up with a local pharmacy to have the vaccine administered. Each participant that was provided with an HPV prescription was contacted after 6 weeks to identify if they received the first dose of vaccine.Outcomes: Yield of our case-finding strategy and receipt of a patient's first HPV vaccine dose during 6 weeks post vaccine prescription. Results: Our case-finding strategy assessed 656 scheduled patients over 4 weeks. From this screening,179 (a case-finding yield of 20.4 %), were candidates for HPV vaccine discussion. Forty-three of these 179 patients (24 %) were already vaccinated.. Two patients (1.1 %) did not consent to be spoken with and 134 (74.8 %) consented to the HPV vaccine discussion.. Forty-eight of 134 patients (35.8 %) of patients accepted a prescription from the dentist after speaking with the dental clinician. Ultimately, 8/48 (16 %) (patients received their first dose of the HPV vaccine by the 6 week of follow-up call. However, this is only 4.5 % (8/177) of those patients who did consent for the discussion of HPV cancers and vaccination from their dentist. Conclusion: We demonstrated that case-finding for HPV vaccine candidates in general dental offices was feasible, with a reasonable yield. While the dental dialogue tool was described as a great resource to explain the facts and answer questions, very few patients were vaccinated after 6 weeks of follow-up. Further work is necessary to sharpen the intervention, perhaps including follow-up discussions with the dental clinicians.