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.

Inclusion of marginalized populations in HPV vaccine modeling: A systematic review.

OBJECTIVE: Models simulating the potential impacts of Human Papillomavirus (HPV) vaccine have been used globally to guide vaccination policies and programs. We sought to understand how and why marginalized populations have been incorporated into HPV vaccine simulation models. METHODS: We conducted a systematic search of PubMed, CINAHL, Scopus, and Embase to identify studies using simulation models of HPV vaccination incorporating one or more marginalized population through stratification or subgroup analysis. We extracted data on study characteristics and described these overall and by included marginalized groups. RESULTS: We identified 36 studies that met inclusion criteria, which modeled vaccination in 21 countries. Models included men who have sex with men (MSM; k = 16), stratification by HIV status (k = 9), race/ethnicity (k = 6), poverty (k = 5), rurality (k = 4), and female sex workers (k = 1). When evaluating for a marginalized group (k = 10), HPV vaccination was generally found to be cost-effective, including for MSM, individuals living with HIV, and rural populations. In studies evaluating equity in cancer prevention (k = 9), HPV vaccination generally advanced equity, but this was sensitive to differences in HPV vaccine uptake and use of absolute or relative measures of inequities. Only one study assessed the impact of an intervention promoting HPV vaccine uptake. DISCUSSION: Incorporating marginalized populations into decision models can provide valuable insights to guide decision making and improve equity in cancer prevention. More research is needed to understand the equity impact of HPV vaccination on cancer outcomes among marginalized groups. Research should emphasize implementation - including identifying and evaluating specific interventions to increase HPV vaccine uptake.

Cost-Effectiveness Analysis of PET-CT Surveillance After Treatment of Human Papillomavirus-Positive Oropharyngeal Cancer.

OBJECTIVE: To determine the cost-effectiveness of surveillance imaging with PET/CT scan among patients with human papillomavirus-positive oropharyngeal squamous cell carcinoma. STUDY DESIGN: Cost-effectiveness analysis. SETTING: Oncologic care centers in the United States with head and neck oncologic surgeons and physicians. METHODS: We compared the cost-effectiveness of 2 posttreatment surveillance strategies: clinical surveillance with the addition of PET/CT scan versus clinical surveillance alone in human papillomavirus-positive oropharyngeal squamous cell carcinoma patients. We constructed a Markov decision model which was analyzed from a third-party payer's perspective using 1-year Markov cycles and a 30-year time horizon. Values for transition probabilities, costs, health care utilities, and their studied ranges were derived from the literature. RESULTS: The incremental cost-effectiveness ratio for PET/CT with clinical surveillance versus clinical surveillance alone was $89,850 per quality-adjusted life year gained. Flexible fiberoptic scope exams during clinical surveillance would have to be over 51% sensitive or PET/CT scan cost would have to exceed $1678 for clinical surveillance alone to be more cost-effective. The willingness-to-pay threshold at which imaging surveillance was equally cost-effective to clinical surveillance was approximately $80,000/QALY. CONCLUSION: Despite lower recurrence rates of human papillomavirus-positive oropharyngeal cancer, a single PET/CT scan within 6 months after primary treatment remains a cost-effective tool for routine surveillance when its cost does not exceed $1678. The cost-effectiveness of this strategy is also dependent on the clinical surveillance sensitivity (flexible fiberoptic pharyngoscopy), and willingness-to-pay thresholds which vary by country.

From planned neck dissection to PET response to circulating tumour DNA: changes in post-treatment assessment of HPV-driven oropharyngeal cancer†.

INTRODUCTION: Circulating tumour human papillomavirus DNA (ctHPVDNA) is an emerging tool to assess post-treatment response in patients with HPV+ oropharyngeal squamous cell carcinoma (OPSCC). Its use is not a standard practice, however, with interval F-18 FDG PET/CT and fiberoptic examination preferred. Post-treatment PET/CT at 3 months has a low positive predictive value (PPV), especially in patients with HPV+ OPSCC treated with (chemo)radiation therapy (CRT). We aimed to compare 3-6 month post-treatment PET/CT and ctHPVDNA test results to determine the most effective option for post-treatment response assessment. METHODS: Patients with HPV+ OPSCC that underwent commercially available ctHPVDNA blood testing after curative intent treatment were identified. Demographic, clinical, treatment, surveillance and oncologic outcome information were collected for each patient. Specificity and false positive rate were calculated for post-treatment PET/CT and ctHPVDNA. RESULTS: 80% of patients had Stage I disease. 52% of the population was treated with definitive chemoradiation (43%) or accelerated radiation (9%), with the remaining patients treated with transoral robotic surgery (TORS) +/- risk-adapted adjuvant therapy. In total, 25 patients underwent ctHPVDNA testing and PET/CT at 3-6 months after finishing treatment. At 3-6 months post-treatment, specificity of ctHPVDNA and PET/CT was 96% and 56%, correlating to false positive rates of 4% and 44%, respectively. CONCLUSIONS: ctHPVDNA is more reliable than PET/CT following treatment in patients with HPV+ OPSCC, and its incorporation in post-treatment response assessment will decrease the rate of anxiety over persistent disease and lead to a decrease in unnecessary medical procedures, including completion of neck dissection.

Assessment of Radiologic Extranodal Extension Using Combinatorial Analysis of Nodal Margin Breakdown and Metastatic Burden in Oropharyngeal Cancer.

The importance of risk stratification in the management of oropharyngeal squamous cell carcinoma (OPSCC) is becoming increasingly obvious with the growing evidence of its variable prognosis. We identified and evaluated imaging characteristics predictive of extranodal extension (ENE) in OPSCC. Preoperative computed tomography and histopathologic results of 108 OPSCC patients who underwent neck dissection as primary treatment were analyzed. Imaging characteristics were reassessed for factors associated with nodal margin breakdown and metastatic burden. Moreover, the predictability of pathological ENE (pENE) was analyzed. Univariate and multivariate binomial logistic regression analyses were performed to examine the predictive power of ENE-related radiologic features. Imaging-based characteristics showed variable degrees of association with pENE. Factors associated with nodal margin breakdown (indistinct capsular contour, irregular margin, and perinodal fat stranding) and factors associated with nodal burden (nodal matting, lower neck metastasis, and presence of >4 lymph node metastases) were significantly predictive of ENE (odds ratio (OR) = 11.170 and 12.121, respectively). The combined utilization of the nodal margin and burden factors further increased the predictive ability (OR = 14.710). Factors associated with nodal margin breakdown and nodal burden were associated with pENE, demonstrating the use of combinatorial analysis for more accurate ENE prediction.

Novel HPV Associated Oropharyngeal Squamous Cell Carcinoma Surveillance DNA Assay Cost Analysis.

OBJECTIVES: We aim to propose a modified surveillance strategy using a novel blood assay that detects plasma circulating tumor-specific HPV DNA with reported 100% NPV and 94% PPV as the main method of detection to understand the cost implications of potentially avoiding routine imaging and surveillance visits at our institution. METHODS: We performed a retrospective chart review focusing on recurrences in p16+ patients with OPSCC and defined two surveillance strategies: "Strategy A", follow-up visits with flexible laryngoscopy (FL) plus regular imaging studies; "Strategy B", follow-up visits with FL plus regular NavDx assays and imaging used at the discretion of the physician(s) in cases of high clinical suspicion. RESULTS: Of the p16+ OPSCC patients (n = 214), 23 had confirmed recurrence (11%). Standard work-flow model determined 72 imaging studies and 2198 physical examinations with FL were needed to detect one recurrence. Potential individual patient cost reduction during surveillance was 42%. CONCLUSION: Implementing NavDx for HPV + OPSCC surveillance would benefit patients by reducing costs and unnecessary diagnostic testing. LEVEL OF EVIDENCE: Step/Level 3 Laryngoscope, 133:3006-3012, 2023.

Extranodal Extension Improves AJCC-8 Accuracy in HPV+ Oropharyngeal Cancer in a High-Risk Population.

OBJECTIVES: The American Joint Committee on Cancer's 8th edition (AJCC-8) separates oropharyngeal squamous cell carcinomas (OPSCCs) into human papillomavirus-positive (HPV+) tumors and HPV-negative tumors. Although AJCC-8 improves prognostic prediction for survival for the majority of HPV+ OPSCC, outliers are still encountered. The goal of this manuscript is to validate the AJCC-8 as a better metric of survivability than the AJCC-7 in an historically under-served rural population with confounding variables, such as tobacco use, alcohol consumption, and poor health care access and to analyze the role of extranodal extension (ENE) in this population. DESIGN: Retrospective cohort study. RESULTS: Compared to AJCC-7, AJCC-8 had a higher odds ratio (OR) for predicting mortality of stage IV HPV+ OPSCCs versus stages I-III. On multivariate analysis, HPV+ OPSCCs with ENE had a higher OR of mortality compared to ENE- OPSCCs. In addition, HPV+ OPSCC patients with a Charlson Comorbidity Index (CCI) > 3 had a higher OR of mortality compared to those with a CCI ≤ 3. Patients with Medicaid/self-pay status had a higher OR of mortality compared to those with private insurance/Medicare. Finally, patients from rural populations had a higher OR of presenting with stage IV disease, a CCI > 3, and Medicaid/self-pay status. CONCLUSIONS: Despite not being a discrete part of the AJCC-8 staging rubric, ENE was found to have a significant impact on mortality among this population, whereas tobacco use had no effect. Rural patients were more likely to present with stage IV disease, CCI > 3, and Medicaid/self-pay status. Stage IV disease was also associated with a higher OR of mortality. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2621-2626, 2023.

Cost-effectiveness of concurrent radiation with cetuximab or chemotherapy in older patients with oropharyngeal cancer.

Aim: To assess the cost-effectiveness of definitive therapies for nonmetastatic oropharyngeal cancer (OPC). Materials & methods: Using the Surveillance, Epidemiology and End Results-Medicare dataset, patients diagnosed between 2000 and 2011 were identified. The cost-effectiveness of chemoradiation (CRT) versus radiotherapy (RT), cetuximab plus RT (cetuximab-RT) versus RT and cetuximab-RT versus CRT were estimated. Results: The incremental cost-effectiveness ratio for CRT compared with RT from 2000 to 2005 was US$56,650 (95% CI: US$4,522-$288,688) per additional year of survival. CRT was dominated by RT from 2006 to 2011. Cetuximab-RT was dominated by RT and CRT. Conclusion: CRT had a favorable value from 2000 to 2005 but was dominated by RT from 2006 to 2011. The value of cetuximab-RT compared with RT/CRT was not favorable with similar/inferior survival and substantial incremental costs.

Increasing HPV vaccination coverage to prevent oropharyngeal cancer: A cost-effectiveness analysis.

The incidence of oropharyngeal cancer (OPC) has been rising, especially among middle-aged men. While Human Papillomavirus (HPV) has been irrevocably implicated in the pathogenesis of oropharyngeal cancer (OPC), the current HPV vaccination uptake rate remains low in the US. The aim of our study was to evaluate the impact of increased HPV vaccination coverage on HPV-associated OPC incidence and costs. A decision analytic model was constructed for hypothetical cohorts of 9-year-old boys and girls. Two strategies were compared: 1) Maintaining the current vaccination uptake rates; 2) Increasing HPV vaccination uptake rates to the Healthy People 2030 target (80%) for both sexes. Increasing HPV vaccination coverage rates to 80% would be expected to prevent 5,339 OPC cases at a cost of $0.57 billion USD. Increased HPV vaccination coverage would result in 7,430 quality-adjusted life year (QALY) gains in the overall population, and it is estimated to be cost-effective for males with an incremental cost-effectiveness ratio of $86,940 per QALY gained under certain conditions. Expanding HPV vaccination rates would likely provide a cost-effective way to reduce the OPC incidence, particularly among males.

Investigating the effect of sexual behaviour on oropharyngeal cancer risk: a methodological assessment of Mendelian randomization.

BACKGROUND: Human papilloma virus infection is known to influence oropharyngeal cancer (OPC) risk, likely via sexual transmission. However, sexual behaviour has been correlated with other risk factors including smoking and alcohol, meaning independent effects are difficult to establish. We aimed to evaluate the causal effect of sexual behaviour on the risk of OPC using Mendelian randomization (MR). METHODS: Genetic variants robustly associated with age at first sex (AFS) and the number of sexual partners (NSP) were used to perform both univariable and multivariable MR analyses with summary data on 2641 OPC cases and 6585 controls, obtained from the largest available genome-wide association studies (GWAS). Given the potential for genetic pleiotropy, we performed a number of sensitivity analyses: (i) MR methods to account for horizontal pleiotropy, (ii) MR of sexual behaviours on positive (cervical cancer and seropositivity for Chlamydia trachomatis) and negative control outcomes (lung and oral cancer), (iii) Causal Analysis Using Summary Effect estimates (CAUSE), to account for correlated and uncorrelated horizontal pleiotropic effects, (iv) multivariable MR analysis to account for the effects of smoking, alcohol, risk tolerance and educational attainment. RESULTS: In univariable MR, we found evidence supportive of an effect of both later AFS (IVW OR = 0.4, 95%CI (0.3, 0.7), per standard deviation (SD), p = < 0.001) and increasing NSP (IVW OR = 2.2, 95%CI (1.3, 3.8) per SD, p = < 0.001) on OPC risk. These effects were largely robust to sensitivity analyses accounting for horizontal pleiotropy. However, negative control analysis suggested potential violation of the core MR assumptions and subsequent CAUSE analysis implicated pleiotropy of the genetic instruments used to proxy sexual behaviours. Finally, there was some attenuation of the univariable MR results in the multivariable models (AFS IVW OR = 0.7, 95%CI (0.4, 1.2), p = 0.21; NSP IVW OR = 0.9, 95%CI (0.5 1.7), p = 0.76). CONCLUSIONS: Despite using genetic variants strongly related sexual behaviour traits in large-scale GWAS, we found evidence for correlated pleiotropy. This emphasizes a need for multivariable approaches and the triangulation of evidence when performing MR of complex behavioural traits.

Cost-utility of two minimally-invasive surgical techniques for operable oropharyngeal cancer: transoral robotic surgery versus transoral laser microsurgery.

BACKGROUND: In the past few decades, a re-evaluation of treatment paradigms of head and neck cancers with a desire to spare patients the treatment-related toxicities of open surgery, has led to the development of new minimally invasive surgical techniques to improve outcomes. Besides Transoral Laser Microsurgery (TLM), a new robotic surgical technique namely Transoral Robotic Surgery (TORS) emerged for the first time as one of the two most prominent and widely used minimally invasive surgical approaches particularly for the treatment of oropharyngeal cancer, a sub-entity of head and neck cancers. Recent population-level data suggest equivalent tumor control, but different total costs, and need for adjuvant chemoradiation. A comparative analysis of these two techniques is therefore warranted from the cost-utility (C/U) point of view. METHODS: A cost-utility analysis for comparing TORS and TLM was performed using a decision-analytical model. The analyses adopted the perspective of a Swiss hospital. Two tertiary referral centers in Lausanne and Zurich provided data for model quantificantion. RESULTS: In the base case analysis TLM dominates TORS. This advantage remains robust, even if the costs for TORS reduce by up to 25%. TORS begins to dominate TLM, if less than 59,7% patients require adjuvant treatment, whereby in an interval between 55 and 62% cost effectiveness of TORS is sensitive to the prescription of adjuvant chemoradiation therapy (CRT). Exceeding 29% of TLM patients requiring a revision of surgical margins renders TORS more cost-effective. CONCLUSION: Non-robotic endoscopic surgery (TLM) is more cost-effective than robotic endoscopic surgery (TORS) for the treatment of oropharyngeal cancers. However, this advantage is sensitive to various parameters, i.e.to the number of re-operations and adjuvant treatment.

Should the HPV positive oropharyngeal cancer patient be considered for a two-stage dental assessment for their radiation treatment?

Patients due to commence head and neck radiation treatment are expected to undergo a dental assessment and be deemed 'dentally fit'. Though this intervention is welcomed by the dental fraternity it is not without its challenges especially in human papilloma virus (HPV) related oropharyngeal cancer (OPC) which has seen a phenomenal rise over the past decade. This perspective piece presents these challenges and proposes a potential adaption of the dental assessment for HPV OPC patients though not necessarily exclusive to this tumour sub-site.

Leveraging Clinical Decision Support and Integrated Medical-Dental Electronic Health Records to Implementing Precision in Oral Cancer Risk Assessment and Preventive Intervention.

INTRODUCTION: Precision medicine is focused on serving the unique needs of individuals. Oral and oropharyngeal cancer risk assessment identifies individual risk factors while providing support to reduce risk. The objective is to examine potential current and future strategies to broadly implement evidence-based oral and oropharyngeal cancer risk assessment and screening in dental practices throughout the United States. METHODS: Feasible and effective oral cancer risk assessment and risk reduction strategies, ripe for implementation in dental practice, were identified in the published literature. RESULTS: The Screening, Brief Intervention, Referral for Treatment (SBIRT) model is a feasible approach to assessing individual oral cancer risk and providing risk reducing interventions in the dental setting. HPV is a more recently identified risk factor that dentistry is well positioned to address. Evidence supporting the utilization of specific risk assessment tools and risk reduction strategies is summarized and future opportunities discussed. DISCUSSION: Current knowledge of risk factors for oral and oropharyngeal cancers support the recommendation for dental providers to routinely assess all patients for risk factors, educate them about their personal level of cancer risk, and recommend actions to reduce relevant risk factors. Individuals ages 9-26 should be asked about their HPV vaccination status, educated about HPV and oropharyngeal cancer and receive a recommendation to get the HPV vaccination.

Corrigendum: Economic Value of Lost Productivity Attributable to Human Papillomavirus Cancer Mortality in the United States.

[This corrects the article DOI: 10.3389/fpubh.2020.624092.].

Optimizing oropharyngeal cancer management by using proton beam therapy: trends of cost-effectiveness.

BACKGROUND: Proton beam therapy (PBT) is a new-emerging cancer treatment in China but its treatment costs are high and not yet covered by Chinese public medical insurance. The advanced form of PBT, intensity-modulated proton radiation therapy (IMPT), has been confirmed to reduce normal tissue complication probability (NTCP) as compared to conventional intensity-modulated photon-radiation therapy (IMRT) in patients with oropharyngeal cancer (OPC). Herein, we evaluated the cost-effectiveness and applicability of IMPT versus IMRT for OPC patients in China, aiming at guiding the proper use of PBT. METHODS: A 7-state Markov model was designed for analysis. Base-case evaluation was performed on a 56-year-old (median age of OPC in China) patient under the assumption that IMPT could provide a 25% NTCP-reduction in long-term symptomatic dysphagia and xerostomia. Model robustness was examined using probabilistic sensitivity analysis, cohort analysis, and tornado diagram. One-way sensitivity analyses were conducted to identify the cost-effective scenarios. IMPT was considered as cost-effective if the incremental cost-effectiveness ratio (ICER) was below the societal willingness-to-pay (WTP) threshold. RESULTS: Compared with IMRT, IMPT provided an extra 0.205 quality-adjusted life-year (QALY) at an additional cost of 34,926.6 US dollars ($), and had an ICER of $170,082.4/ QALY for the base case. At the current WTP of China ($33,558 / QALY) and a current IMPT treatment costs of $50,000, IMPT should provide a minimum NTCP-reduction of 47.5, 50.8, 55.6, 63.3 and 77.2% to be considered cost-effective for patient age levels of 10, 20, 30, 40 and 50-year-old, respectively. For patients at the median age level, reducing the current IMPT costs ($50,000) to a $30,000 level would make the minimum NTCP-reduction threshold for "cost-effective" decrease from 91.4 to 44.6%, at the current WTP of China (from 69.0 to 33.5%, at a WTP of $50,000 / QALY; and from 39.7 to 19.1%, at a WTP of $100,000 / QALY). CONCLUSIONS: Cost-effective scenarios of PBT exist in Chinese OPC patients at the current WTP of China. Considering a potential upcoming increase in PBT use in China, such cost-effective scenarios may further expand if a decrease of proton treatment costs occurs or an increase of WTP level.

The role of insurance status as a mediator of racial disparities in oropharyngeal cancer outcomes.

BACKGROUND: To assess the role of insurance status as a mediator of racial disparities in oropharyngeal cancer outcomes. METHODS: This was a population-based retrospective cohort study. Data were extracted from the Surveillance, Epidemiology, and End Results 18 database. The study cohort included 11 627 patients diagnosed with oropharyngeal squamous cell carcinoma between 2010 and 2015. RESULTS: The association between black race and increased risk of unresectable disease was slightly attenuated, but persistent, after including insurance status as a covariate (odds ratio [OR] 1.34, 95%CI 1.10-1.63). Likewise, black race was no longer associated with worse disease-specific survival (hazard ratio [HR] 1.11, 95%CI 0.99-1.26), but remained associated with worse overall survival with a slightly decreased effect size (HR 1.13, 95%CI 1.01-1.25). CONCLUSIONS: Insurance status plays a significant role in, but does not completely account for, the persistent racial disparities in oropharyngeal cancer outcomes.

Cost-Effectiveness Models of Proton Therapy for Head and Neck: Evaluating Quality and Methods to Date.

PURPOSE: Proton beam therapy (PBT) is associated with less toxicity relative to conventional photon radiotherapy for head-and-neck cancer (HNC). Upfront delivery costs are greater, but PBT can provide superior long-term value by minimizing treatment-related complications. Cost-effectiveness models (CEMs) estimate the relative value of novel technologies (such as PBT) as compared with the established standard of care. However, the uncertainties of CEMs can limit interpretation and applicability. This review serves to (1) assess the methodology and quality of pertinent CEMs in the existing literature, (2) evaluate their suitability for guiding clinical and economic strategies, and (3) discuss areas for improvement among future analyses. MATERIALS AND METHODS: PubMed was queried for CEMs specific to PBT for HNC. General characteristics, modeling information, and methodological approaches were extracted for each identified study. Reporting quality was assessed via the Consolidated Health Economic Evaluation Reporting Standards 24-item checklist, whereas methodologic quality was evaluated via the Philips checklist. The Cooper evidence hierarchy scale was employed to analyze parameter inputs referenced within each model. RESULTS: At the time of study, only 4 formal CEMs specific to PBT for HNC had been published (2005, 2013, 2018, 2020). The parameter inputs among these various Markov cohort models generally referenced older literature, excluding many clinically relevant complications and applying numerous hypothetical assumptions for toxicity states, incorporating inputs from theoretical complication-probability models because of limited availability of direct clinical evidence. Case numbers among study cohorts were low, and the structural design of some models inadequately reflected the natural history of HNC. Furthermore, cost inputs were incomplete and referenced historic figures. CONCLUSION: Contemporary CEMs are needed to incorporate modern estimates for toxicity risks and costs associated with PBT delivery, to provide a more accurate estimate of value, and to improve their clinical applicability with respect to PBT for HNC.

A cost-utility analysis comparing CT surveillance, PET-CT surveillance, and planned postradiation neck dissection for advanced nodal HPV-positive oropharyngeal cancer.

BACKGROUND: The cost utility of image-guided surveillance using computed tomography (CT) and positron emission tomography (PET)-CT to planned postradiation neck dissection (PRND) was compared for the management of advanced nodal human papillomavirus-positive oropharyngeal cancer following chemoradiation. METHODS: A universal payer perspective was adopted. A Markov model was designed to simulate four treatment approaches with 3-month cycles over a lifetime horizon: 1) CT surveillance, 2) standard PET-CT surveillance, 3) a novel PET-CT approach with repeat PET at 6 months postchemoradiation for equivocal responders, and 4) PRND. Parameters including probabilities of CT nodal progression/resolution, PET avidity, recurrence, and survival were obtained from the literature. Costs were reported in 2019 Canadian dollars and utilities were expressed in quality-adjusted life years (QALYs). Deterministic and probabilistic sensitivity analyses were performed to evaluate model uncertainty. RESULTS: PET-CT surveillance dominated CT surveillance and PRND in the base case scenario, and the novel PET-CT approach was the most cost-effective strategy across a wide range of variables tested in one-way sensitivity analysis. On probabilistic sensitivity analysis, novel PET-CT surveillance was the most cost-effective strategy in 78.1% of model iterations at a willingness-to-pay of $50,000/QALYs. Novel PET-CT surveillance resulted in a 49% lower rate of neck dissection compared with traditional PET-CT, and yielded an incremental benefit of 0.14 QALYs with average cost savings of $1309. CONCLUSIONS: Image-guided surveillance including PET-CT and CT are more cost effective than PRND. The novel PET-CT approach with repeat PET for equivocal responders was the dominant strategy and yielded both higher benefit and lower costs compared with standard PET-CT surveillance.

Tonsillectomy as a Prevention Strategy in the Light of Increasing Incidence of Oropharyngeal Cancer - a Research of Current Literature.

BACKGROUND/AIM: While in many Western countries the number of tonsillectomies decreases significantly, there is an increasing incidence of oropharyngeal carcinomas. For, obviously, removal of the tonsils will reduce individual risk for tonsil cancer, the question of tonsillectomy as a prevention strategy is suggested. This study focused on this question by carrying out a literature research. MATERIALS AND METHODS: A literature research was performed (www.pubmed.gov; Search words: tonsillectomy, oropharyngeal cancer, tonsil cancer, prevention) without applying additional filters. RESULTS: Out of the 16 identified studies, three population-based studies were evaluated. Individual incidence of tonsil cancer is significantly lower after removal of tonsils; however, risk elimination by tonsillectomy has not been proven. One of the studies revealed increasing numbers of base of the tongue cancer after previous tonsillectomy. CONCLUSION: The increase in oropharynx carcinomas can currently be attributed not to the decreasing tonsillectomy rates, but to the increase in HPV infections. A previous tonsillectomy reduces the individual risk of developing tonsil carcer. Tonsillectomy as prevention for oropharyngeal cancer cannot be recommended and may even be a disadvantage concerning base of the tongue cancers.

Disease Profile and Oncologic Outcomes After Delayed Diagnosis of Human Papillomavirus-Associated Oropharyngeal Cancer.

OBJECTIVE: Diagnostic delay in human papillomavirus-associated oropharynx squamous cell carcinoma (HPV(+)OPSCC) is common due to nonspecific symptoms. We aim to describe the disease burden and oncologic outcomes of patients with HPV(+)OPSCC diagnosed >12 months after symptom onset. STUDY DESIGN: This is a retrospective cohort study of HPV(+)OPSCC patients receiving intent-to-cure treatment (including surgery ± adjuvant therapy or primary chemoradiation). SETTING: 2006-2016, tertiary care center. METHODS: Tumor stage was compared between patients with and without delayed diagnosis using χ2 tests. Kaplan-Meier survival analysis with univariate and multivariable Cox regressions were used to determine the effect of diagnostic delay on oncologic outcomes. RESULTS: In total, 664 patients were included. Compared to patients diagnosed <12 months from symptom onset (n = 601), those diagnosed at >12 months (n = 63) were more likely to have T4 disease and higher overall American Joint Committee on Cancer (AJCC) clinical stage at presentation (P < .01 for both). At 5 years, rates of overall survival, cancer-specific survival, progression-free survival, and distant metastases-free survival in the delayed diagnosis cohort were 80%, 90%, 80%, and 89%, respectively. A >12-month delay in diagnosis did not significantly impact overall survival (adjusted hazard ratio [aHR], 1.16; 95% CI, 0.58-2.31), cancer-specific survival (aHR, 0.83; 95% CI, 0.29-2.39), progression-free survival (aHR, 1.15; 95% CI, 0.56-2.37), or distant metastases-free survival (aHR, 1.00; 95% CI, 0.42-2.40) after adjusting for age, sex, and clinical AJCC stage (P > .05 for all). CONCLUSIONS: Delayed diagnosis of HPV(+)OPSCC is associated with greater burden of disease at presentation, but oncologic outcomes remain favorable across treatment modalities. When appropriate, intent-to-cure therapy should be pursued despite diagnostic delay. LEVEL OF EVIDENCE: Level III.