HPV-positive Oropharyngeal Cancer Research Articles

Translational risk-adapted approaches to de-escalated radiation for human papillomavirus-positive oropharyngeal cancer: Past, present, and future

Interest in the use of de-escalated radiation to treat patients with newly diagnosed human papillomavirus (HPV)-positive oropharyngeal cancer has grown dramatically with the publication of prospective trials demonstrating the efficacy of such an approach. While the rationale for de-escalation--- namely to decrease treatment-related toxicity while maintaining the excellent rates of disease control historically observed in patients with this disease—is inherently obvious, uncertainty exists regarding how to best select patients for de-escalation. Consequently, risk-adapted strategies using a variety of translational and clinical platforms have been increasingly popularized to better refine treatment. These have integrated contemporary methods of mid-treatment response assessment using advanced technologies and molecular assays to customize the radiation dose. By monitoring the response as patients actively proceed through treatment, risk-adapted protocols have the potential to provide insight into the biological behavior of tumors and make individualized therapy possible. The purpose of this review is to summarize the evidence to date on risk-adapted approaches to de-escalated radiation-- highlighting the clinical, radiological, and biological data which may ultimately help usher the principles of precision medicine into practice for patients with HPV-positive oropharyngeal cancer.

Prospective manipulation of the gut microbiome with microbial ecosystem therapeutic 4 (MET4) in HPV-related locoregionally-advanced oropharyngeal cancer squamous cell carcinoma (LA-OPSCC) undergoing primary chemoradiation: ROMA2 study.

Gut microbiome modulation to boost antitumor immune responses is under investigation. ROMA-2 evaluated the microbial ecosystem therapeutic (MET)-4 oral consortia, a mixture of cultured human stool-derived immune-responsiveness associated bacteria, given with chemoradiation (CRT) in HPV-related oropharyngeal cancer patients. Co-primary endpoints were safety and changes in stool cumulative MET-4 taxa relative abundance (RA) by 16SRNA sequencing. Stools and plasma were collected pre/post-MET-4 intervention for microbiome and metabolome analysis. Twenty-nine patients received ≥1 dose of MET-4 and were evaluable for safety: drug-related adverse events (AEs) occurred in 13/29 patients: all grade 1-2 except one grade 3 (diarrhea). MET-4 was discontinued early in 7/29 patients due to CRT-induced toxicity, and in 1/29 due to MET-4 AEs. Twenty patients were evaluable for ecological endpoints: there was no increase in stool MET-4 RA post-intervention but trended to increase in stage III patients (p = 0.06). MET-4 RA was higher in stage III vs I-II patients at week 4 (p = 0.03) and 2-month follow-up (p = 0.01), which correlated with changes in plasma and stool targeted metabolomics. ROMA-2 did not meet its primary ecologic endpoint, as no engraftment was observed in the overall cohort. Exploratory findings of engraftment in stage III patients warrants further investigation of microbiome interventions in this subgroup.

Biplex quantitative PCR to detect transcriptionally active human papillomavirus 16 from patient saliva

Head and neck cancers, particularly oropharyngeal cancers (OPC), have been increasingly associated with human papillomavirus (HPV) infections, specifically HPV16. The current methods for HPV16 detection primarily rely on p16 staining or PCR techniques. However, it is important to note the limitations of conventional PCR, as the presence of viral DNA does not always indicate an ongoing viral infection. Moreover, these tests heavily rely on the availability of tissue samples, which can present challenges in certain situations. In this study, we developed a RT-qPCR biplex approach to detect HPV16 oncogenes E6 and E7 RNA in saliva samples from OPC patients. Salivary supernatant was used as the liquid biopsy source. We successfully obtained RNA from salivary supernatant, preserving its integrity as indicated by the detection of several housekeeping genes. Our biplex approach accurately detected E6 and E7 RNA in HPV16-positive cell lines, tissues, and finally in OPC salivary samples. Importantly, the assay specifically targeted HPV16 and not HPV18. This biplexing technique allowed for reduced sample input without compromising specificity. In summary, our approach demonstrates the potential to detect viable HPV16 in saliva from OPC patients. Since the assay measures HPV16 RNA, it provides insights into the transcriptional activity of the virus. This could guide clinical decision-making and treatment planning for individuals with HPV-related OPC.

"I'm Torn": Qualitative Analysis of Dental Practitioner-Perceived Barriers, Facilitators, and Solutions to HPV Vaccine Promotion.

The human papillomavirus (HPV) vaccine can prevent HPV-related oropharyngeal cancers. Dental practitioners are uniquely positioned to promote HPV vaccines during routine dental care but experience barriers to doing so. Qualitative interviews were conducted with dental practitioners to understand barriers and inform intervention strategies to promote HPV vaccines. Dental practitioners were invited to participate in phone interviews about knowledge, self-efficacy, and the fear of negative consequences related to HPV vaccine promotion as well as feedback on potential interventions to address these barriers. Interviews were audio recorded, transcribed, and analyzed using rapid qualitative analysis with a sort-and-sift matrix approach. Interviews were completed with 11 practitioners from six dental clinics (avg. 31 min). Though most thought HPV vaccination was important, they lacked detailed knowledge about when and to whom the vaccine should be recommended. This led to a hypothesized need for discussions of sexual history, feelings of limited self-efficacy to make the recommendation, and fear of patient concerns. Still, practitioners were supportive of additional training opportunities and provided input into specific interventions. The nuance of how these barriers were described by practitioners, as well as the possible solutions they identified, will help shape future interventions supporting HPV vaccine promotion in dental care.

Does Sexual Behaviors Account for HPV-related Oropharyngeal Cancer (OPC)?

Introducción: El virus del papiloma humano (VPH) es una infección de transmisión sexual que se ha relacionado estrechamente con el cáncer de orofaringe. Alguna evidencia sugiere que los comportamientos sexuales pueden aumentar el riesgo de cáncer de orofaringe. Objetivos: Hacer una revisión de la información existente sobre el cáncer orofaríngeo asociado al VPH y su relación con conductas sexuales. Metodología: Se utilizó Google Scholar para buscar bases de datos electrónicos de casos clínicos y artículos de revisión sobre cáncer orofaríngeo relacionado al VPH desde el 2020 al 2023. Resultados: Ocho estudios revelaron que ciertas prácticas sexuales pueden aumentar el riesgo de cáncer de orofaringe, mientras que 2 estudios europeos afirman que no existe correlación entre las infecciones por VPH y los hábitos sexuales. Conclusiones: Las prácticas sexuales seguras pueden reducir el riesgo de infecciones por VPH y el riesgo de desarrollar cáncer de orofaringe. Área de estudio general: Medicina. Área de estudio específica: Virología. Tipo de estudio: revisión bibliográfica.

EGFR overexpression and macrophage infiltration correlate with poorer prognosis in HPV-negative oropharyngeal cancer via STAT6 signaling.

The prevalence of HPV-negative oropharyngeal cancer (OPC) is higher in Asian countries. Patients with HPV-negative OPC suffer poor outcomes. Multi-omics analysis could provide researchers and clinicians with more treatment targets for this high-risk group. We aimed to explore the prognostic significance of EGFR overexpression and macrophage infiltration in OPC, especially HPV-negative OPC in this study. EGFR alternation was evaluated with TCGA, PanCancer Atlas through cBioProtal. EGFR mRNA expression in HPV-negative head and neck squamous cell carcinoma was analyzed using the Tumor Immune Estimation Resource (TIMER 2.0). We also examined EGFR/STAT6/MRC1 expression in paraffin-embedded tissues from a p16-negative OPC cohort. The correlation between EGFR expression and macrophage activation was explored using Person's correlation coefficient. The impact of biomarkers or macrophage infiltration on 5-year overall survival and recurrence-free survival were analyzed using Kaplan-Meier survival curves. EGFR alteration rate was 15%, 13%, and 0% for HPV-negative HNSCC (excluding OPC), HPV-negative OPC, and HPV-positive OPC. High EGFR expression was associated with increased tumor infiltration of immune cells, such as macrophages. We observed positive correlations between EGFR, STAT6, and MRC1 expression in p16-negative OPC. Higher MRC1 expression was associated with poorer survival rates. There is strong correlation between EGFR overexpression and M2 polarization in patients with p16-negative OPC. Immunotherapy with or without EGFR inhibitor could be considered in these high-risk patients.

The role of surgery and deescalation for HPV-related oropharyngeal cancer.

Recently published and ongoing trials are helping to define the role of transoral robotic surgery for oropharyngeal cancer. Evidence to date supports the use of surgery as a valuable tool in the multidisciplinary deescalation of low-risk human papillomavirus-related oropharyngeal squamous cell carcinoma.

Pretreatment Circulating HPV16 DNA Viral Load Predicts Risk of Distant Metastasis in Patients with HPV16-Positive Oropharyngeal Cancer.

There are definite reasons to implement molecular diagnostics based on the measurement of human papillomavirus (HPV) DNA in liquid biopsy into clinical practice. It is a quick, repeatable, and health-safe test for cancer biomarkers in the blood. In this study, we investigated whether the circulating tumor-related HPV16 (ctHPV16) viral load (VL) in patients with oropharyngeal squamous cell carcinoma (OPSCC) was important for determining the risk of locoregional recurrence-free survival (LRFS), metastasis-free survival (MFS), and overall survival (OS). This study included 91 patients with ctHPV16-positive OPSCC who had been treated with radical radiotherapy and chemotherapy. The VL was measured using quantitative PCR (qPCR) and a probe specific for HPV16. Based on 10 years of follow-up, the 2-, 3-, 5-, and 9-year LRFS, MFS, and OS were estimated. The 5-year actuarial LRFS, MFS, and OS rates of patients with ctHPV16-positive/OPSCC were 88%, 90%, and 81%, respectively. The VL was significantly higher in patients who subsequently developed distant metastases (DM) than in those who did not (VL 4.09 vs. 3.25; p = 0.009). In a Cox proportional hazards regression model for MFS, a higher ctHPV16 VL appeared to be a significant independent prognostic factor for the occurrence of DM (HR 2.22, p = 0.015). The ROC curve revealed a cutoff value of 3.556 for VL (p = 0.00001). A high VL before treatment indicates patients with a significant risk of DM, and should be used in OPSCC treatment stratification.

Biomarker-Driven Radiation Therapy Dose Reduction after Transoral Robotic Surgery for the Treatment of HPV-Positive Oropharyngeal Cancer

Biomarker-Driven Radiation Therapy Dose Reduction after Transoral Robotic Surgery for the Treatment of HPV-Positive Oropharyngeal Cancer

Sexual history of patients with human papillomavirus positive and negative oropharyngeal cancer: A systematic review and meta-analysis.

Increased sexual activity is associated with higher human papillomavirus (HPV) rates; however, there is a lack of analysis comparing the sexual history of patients with HPV positive and HPV negative oropharyngeal cancer (OPC). In this meta-analysis, PubMed, Scopus, and CINAHL were searched for articles that included patients with OPC and reported information regarding HPV status and either history of oral sex, number of sexual partners, or sexually transmitted infections (STI). A total of 11 studies were included with 3296 patients with OPC. Patients with HPV positive OPC were more likely than patients with HPV negative OPC to report a history of oral sex (92%, 95% CI: 87.0-97.0 vs. 74.5%, 95% CI: 50.6-98.4, p < 0.0001), higher mean number of sexual partners (18.4 partners, 95% CI: 1.5-35.4 vs. 7.2 partners, 95% CI: 1.0-13.4, p < 0.0001), and more frequent history of STI (23.7%, 95% CI: 18.4-29.0 vs. 8.8%, 95% CI: 4.7-12.8, p = 0.0001). Compared to patients with HPV negative OPC, our analysis shows a larger proportion of patients with HPV positive OPC had participated in oral sex, had a higher number of sexual partners, and had a higher proportion of STI history.

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

PurposeThe 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. MethodsThis 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. ResultsOf 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. ConclusionThe 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.

Population-level incidence of HPV-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 cases were among persons who ever smoked. Population-level incidence rate was higher among persons who ever smoked than never smoked for HPV-positive oropharyngeal (7.8 vs 2.1; adjusted incidence rate ratio [RRadj] = 2.6), cervical (13.7 vs 6.8; RRadj = 2.0), and anal (3.9 vs 1.6; RRadj = 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 persons who ever smoked.

75 Inflammation and post-tx sickness syndrome as an explanation for late effects

The changing epidemiology of head and neck cancer, with an increase in HPV-positive oropharyngeal cancers and the refinement of a multidisciplinary approach, has led to an increase in the prevalence of long-term survivors after treatment. Consequently, a higher proportion of patients are suffering from late effects of the treatments, temporally defined as effects occurring or persisting more than 3 months after the end of the treatments. These late toxicities consist both of locoregional problems and systemic syndromes, with an impact on patients’ quality of life.There is still limited knowledge about the precise causes of these late toxicities, and at the same level, we lack predictive factors able to identify patients at higher risk of late effects. Treatment combinations with surgery followed by (chemo)radiation or with chemotherapy added to radiation with a radiosensitizing effect increase the probability of suffering from the late consequences of the same therapies. Pain, swallowing difficulties, trismus, osteonecrosis, dental disorders, mucositis, xerostomia or sticky saliva, hoarseness, lymphedema, and fibrosis are the most reported symptoms and signs, while fatigue, anxiety, depression, and cognitive impairment are the counterparts at the systemic level.There is growing evidence for the role of inflammation in the progression of cancer and treatment-related side effects. However, for head and neck cancer patients, there are still a lot of unanswered questions related to the role of inflammation as being both related to cancer disease and to the consequences of the intensive treatments carried out for this disease. In particular, it is well known that pro-inflammatory cytokines have been shown to be activated by malignant tumors and cancer treatment, and that their level during treatment is linked to higher acute toxicities. Also, the level of pro-inflammatory cytokines such as interleukin (IL)-1 beta (IL-1β), IL-6, IL-8, and tumor necrosis factor (TNF) has been correlated to higher mucositis, dysphagia, and pain due to the acute toxic effect of chemoradiation. However, researchers have not yet proven the association between the level of proinflammatory cytokines in the acute phase of the treatment and the development of late toxicities. Even the role of the same pro-inflammatory mediators in the follow-up period has a conflicting correlation with the late toxicities reported by the patients. Chronic inflammation may cause fibrosis, one of the key pathological features of radiation-induced late effects such as dysphagia and transforming growth factor beta (TGF-β) and TNF are involved in the formation of fibrosis in irradiated tissue. There is even more debate about the cause of systemic symptoms after cancer treatment. Head and neck cancer patients may develop the post-treatment sickness syndrome, consisting of chronic fatigue, mood alteration, cognitive impairment, and sleep problems, among the most frequently reported symptoms. The neuro-behavioral sickness model recapitulates all these symptoms as being related to the stress induced by the treatment, causing alterations in mood, cognition, nutritional intake, and the neurovegetative system. One of the hypotheses is that activation of peripheral pro-inflammatory cytokine networks transmits signals to the brain, which promote sickness behavior. The tissue damage induced by the oncological treatments would result in a self-perpetuating activation of biological processes, leading to a persistent inflammation condition that results in worsening systemic late effects over time. However, this theory needs to be carefully validated with prospective studies exploring patient-reported outcomes and their correlation with inflammatory mediators. According to this model, if inflammation recapitulates the locoregional and systemic late toxicities induced by the treatments, research should lead efforts to find ways to counteract it. From one side, it is possible to define de-escalating treatments that could offer the same level of cancer control with a reduced burden of acute and late toxicities. This is particularly awaited in HPV-positive cancer patients, who are usually younger patients, obtaining higher survival rates and thus a higher impact of toxicities on quality of life. On the other hand, it is important to define specific protocols to reduce the impact of inflammation in the long-term. In this regard, the role of physical exercise has been clearly underestimated, and recent research has shown benefits for the survival and quality of life of head and neck cancer patients. Also, even with less scientific evidence, nutrition could offer a less inflamed systemic status that could help minimize the late effects of cancer treatment. It is clear that research in this field is in its infancy, and we need to put more efforts into defining the translational correlates of late toxicities and exploring new ways to counteract the post-treatment sickness syndrome.

270 Radiologic diagnosis of Extranodal Extension (ENE) in patients with HPV-positive oropharyngeal cancer: consensus diagnosis and influence on prognosis

Tumor often progresses through the weakest part of any surrounding tissues. The extent of tumor invasion depends on: a. Aggressiveness of the tumor cells (e.g. number and invasive character of stem cells), b. robustness of the surrounding tissues and their composition (e.g. vessels), and c. time to allow the tumor to proliferate. The lymph node (LN) capsule comprises dense connective tissue stroma and collagenous fibers, and is a natural barrier that generally prevents further tumor progression. Permeation of tumor through the nodal capsule into surrounding tissues is termed “extranodal extension”. The idiosyncratic and inconsistent mechanism of ENE is imprecisely understood, but it is thought to be due to either tumor cell proliferation that outpaces the capacity of nodal capsular expansion (“ruptures” the LN capsule), or factors within the tumor or tumor microenvironment that facilitate the “breach” of the capsule. The latter might explain ENE in small LNs, or a “neglected” tumor (lengthy intranodal tumor growth with eventual “rupture” through an expanded nodal capsule). Several biomarkers (e.g. podoplanin) that are often associated with tumor aggressiveness have been reported to have a high expression in ENE+ LN. ENE represents a spectrum of tumor nodal invasion. The early sign of ENE can only be visible under the microscope (pathologic ENE); when ENE progresses further, the radiographic signal changes become apparent, making it visible on imaging (iENE). Most advanced ENE causes emergence of clinical surrogates (e.g. peau d'orange, or a “fixed” nodal mass), rendering it detectable by regular clinical examination (ENEc). iENE has been reported to be one of the strongest anatomic prognostic factors for overall survival (mainly due to increased risk of distant metastasis) in HPV-positive oropharyngeal carcinoma (HPV+ OPC), and is able to identify a subgroup of stage I disease with poor prognosis. Several deintensification trials (NRG-HN002, ORATOR, ORATOR2, E3311) have excluded HPV+ OPC with some form of iENE from trial enrolment. Several authors have proposed that iENE be included in future clinical N classification for HPV+ OPC. However, adoption of iENE in clinical care remains challenging because it is not a well-defined radiologic feature among the radiology community. Various definitions / descriptions of iENE have been used in literature. There is also insufficient awareness of the prognostic importance of this parameter in head and neck oncology community. The international iENE Expert Panel was convened under the HNCIG comprised expert internationally renowned neuroradiologists and clinicians. Several rounds of Delphi process were conducted to consolidate iENE definition. The consensus recommendations on the terminology and diagnostic criteria for iENE were generated. The experts in the consensus process recognized the following as criteria for the diagnosis of iENE: clear evidence of irregular or indistinct nodal margin/border; extension into perinodal fat; extension into adjacent structures, and conglomerate/matted/coalescent nodes. These recommendations have been endorsed by 19 national organisations, representing 34 countries. With increased awareness and consolidated definition as well as training, iENE could become an important baseline factor for risk stratification and staging in HPV+ OPC.

145 Survival outcomes of elderly patients treated with a curatively-intended treatment for HPV-related oropharyngeal cancer: a multicenter cohort study

145 Survival outcomes of elderly patients treated with a curatively-intended treatment for HPV-related oropharyngeal cancer: a multicenter cohort study

Consideration of liquid biomarkers for surveillance of HPV-related oropharyngeal cancer in veteran populations

The incidence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) will continue to rise in the United States over the next several decades. Thus, efforts to reduce treatment intensity, mitigate long-term physical and psychological sequelae of treatment, and simplify surveillance regimens for patients with HPV-related OPSCC are critical. Liquid biomarkers, namely plasma circulating tumor HPV DNA (ctDNA), have shown considerable promise for improvements in these domains by guiding personalized and adaptive treatment de-escalation paradigms and predicting disease recurrence in the survivorship period. Preliminary reports suggest an even broader impact of plasma HPV ctDNA assays for HPV-related OPSCC surveillance beyond the mere detection of cancer recurrence and metastasis. For instance, such assays may reduce the need for costly imaging studies, alleviate the financial toxicities of survivorship care, and improve care access and patient satisfaction. Currently, veterans and underserved populations are disproportionately affected by the financial burden of cancer surveillance and survivorship care. These disparities negatively impact oncologic outcomes, healthcare access, and utilization, specifically among veterans with HPV-related OPSCC. As such, we posit that HPV ctDNA monitoring may be of unique benefit and impact in the surveillance period for these patients specifically. Herein, we provide a narrative review of the current literature supporting the formal clinical evaluation of HPV ctDNA monitoring in veterans with HPV-related OPSCC.

Improving HPV-Related Oropharyngeal Cancer Knowledge and HPV Vaccination Rates via Virtual Workshops.

To validate the efficacy of a virtual, interdisciplinary workshop in improving HPV knowledge, and vaccination practices among primary care and dental trainees. A virtual platform was utilized to hold HPV educational workshops with primary care and dental trainees. Online surveys were distributed before and after the 1-h interactive workshop, led by otolaryngology residents. Surveys included the workshop's impact on (a) improving knowledge of HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) and (b) affecting change in HPV vaccination practices. The vaccination rates of trainees were recorded prior to and after workshop attendance. After the workshop, participants demonstrated significantly improved scores related to knowledge of HPV in the head and neck (p = 0.003) and showed an increased comfort level with counseling on HPV vaccination (p = 0.002). Respondents were also more aware that the HPV vaccine is approved to prevent OPSCC (61% vs. 95%, p < 0.05). Ninety-seven percent of respondents stated that the workshop changed their HPV vaccination practices, and 95% of those not fully vaccinated stated they would now be more likely to receive the vaccine themselves. There was a significant increase in the average number of HPV vaccines administered at the studied trainee clinic, from 16.83 vaccines/month to 37.6 vaccines/month (percent increase = 123%) in 5 months following the workshop (p = 0.002). The present interactive virtual workshop demonstrates efficacy in improving HPV-related knowledge and vaccination practices among trainees. The virtual nature of the course facilitates knowledge transfer and can be used to foster multi-institutional partnerships regarding medical education and vaccination efforts. 4 Laryngoscope, 2024.

Extra-Capsular Spread of Lymph Node Metastasis in Oral, Oropharyngeal and Hypopharyngeal Cancer: A Comparative Subsite Analysis

Background: The extra-capsular spread (ECS) of lymph node metastasis (LNM) is a hallmark of aggressive primary tumor phenotype in head and neck cancer (HNC); however, the factors influencing ECS are poorly understood. Patients and Methods: This was a retrospective study, including 190 cases of oral tongue cancer (OTC), 148 cases of oropharyngeal cancer (OPC) (118 HPV-positive and 30 HPV-negative), and 100 cases of hypopharyngeal cancer (HPC). Tumor dimension, tumor biological variables (lymphovascular/perineural invasion and histologic grade), and LNM variables (LNM number and size) were analyzed according to the presence of ECS using multivariable logistic regression and receiver operating characteristic (ROC) curve analyses. Results: LNM variables were significant factors for ECS in all subsites of HNC (p &lt; 0.05), except HPV-positive OPC. In OTC, tumor dimensional variables were significantly related to ECS (p &lt; 0.01). Meanwhile, in OPC and HPC, neither the primary tumor dimension nor the T status were significant factors for ECS occurrence. The predictability of ECS by ROC curve using multiple variables was 0.819 [95% confidence interval: 0.759–0.878] in OTC, 0.687 [0.559–0.815] in HPV-positive OPC, 0.823 [0.642–1.000] in HPV-negative OPC, and 0.907 [0.841–0.973] in HPC. Conclusion: LNM variables were correlated with ECS occurrence for most HNC subsites, and site-dependent primary tumor characteristics might contribute differentially to the ECS development of LNM in HNC.

Impact of pretreatment body mass index on the survival of head and neck cancer patients.

Differences in pretreatment body mass index (BMI) have been associated with survival in squamous cell carcinoma of head and neck (SCCHN). We examined effects of BMI on survival in SCCHN patients after stratifying patients by tumor human papillomavirus (HPV) status and subsite. Totally 2204 SCCHN patients in a prospective study were included in this secondary analysis. Multivariable Cox models were used to evaluate associations between pretreatment BMI and overall survival, disease-specific survival, and disease-free survival. BMI was significantly higher among patients with HPV-positive tumors than HPV-negative tumors. BMI >25 kg/m2 was associated with improved survival, while BMI <18.5 kg/m2 was associated with reduced survival, particularly in patients with HPV-positive oropharyngeal cancer tumors. This exploratory analysis suggests that pretreatment BMI could be an independent prognostic factor of survival outcomes in SCCHN patients, particularly in patients with HPV-positive oropharyngeal cancer tumors. Further prospective investigations are warranted.

Screening for HPV-Related Oropharyngeal Cancer in Gay and Bisexual Men: Acceptability and Predicting Possible Use of "Oral Selfies" by Smartphone as a Secondary Prevention Approach.

Oropharyngeal cancers (OPCa) caused by HPV have emerged as one of the leading causes of malignancies caused by HPV infection. They are also significantly more likely to occur in males and in people with a history of oral sex with multiple partners. Gay and bisexual men are disproportionately affected by HPV-positive oropharyngeal cancers. We studied 1699 gay and bisexual men on 2 major dating sites in the US to assess their knowledge about HPV-related OPCa, attitudes toward screening for it, beliefs about oropharyngeal cancer screening based on the Health Belief Model, and attitudes toward possible screening approaches for OPCa. Knowledge on a 12-item scale was low, with a median of 5 items correct: 72% knew of the benefits of HPV vaccination. Significant predictors of needing OPCa screening included perception of risk for OPCa, seeing it as severe, having lower barriers, fewer reasons to avoid screening, higher knowledge, and being HPV vaccinated were significant predictors, explaining half the total variance. Most participants would accept routine, virtual/online doctor or dental appointments, and over half would accept an in-person screening. Nearly two-thirds stated that they would accept getting checked for OPCa if they could do self-screening at home, and half were prepared to use an online screening tool or app, where they could take an "oral selfie" and send it to a healthcare provider for examination. One-third stated that they would trust the results of a home screening completed by themselves and posted to a website equally as cancer screening completed online by a healthcare provider. Data indicate that despite low OPCA knowledge levels, the risk of HPV-associated OPCa was known. Being at personal risk and having knowledge of disease severity had 70% of the sample thinking about, or preparing to get, screening. Self-screening by a smartphone "oral selfie" transmitted to a screening website was acceptable to many gay and bisexual men, and online screening by a doctor or dentist was acceptable to most. OPCa screening in this population using electronic technology, together with the increasing incidence of HPV-associated OPCa in gay and bisexual men, brings together an opportunity to detect OPCa early.