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Purpose To report patient-reported outcomes (PROs) derived from the Functional Assessment of Cancer Therapy-Head and Neck (FACT-HN) tool, in patients with oropharynx cancer (OPC) treated with intensity-modulated proton therapy (IMPT) in the context of first-course irradiation. Materials and Methods Patients with locally advanced OPC treated with radical IMPT between 2011 and 2018 were included in a prospective registry. FACT-HN scores were measured serially during and 24 months following IMPT. PRO changes in the FACT-HN scores over time were assessed with mixed-model analysis. Results Fifty-seven patients met inclusion criteria. Median age was 60 years (range, 41-84), and 91% had human papillomavirus-associated disease. In total, 28% received induction chemotherapy and 68% had concurrent chemotherapy. Compliance to FACT-HN questionnaire completion was 59%, 48%, and 42% at 6, 12, and 24 months after treatment, respectively. The mean FACT-General (G), FACT-Total, and FACT-Trial Outcome Index (TOI) score changes were statistically and clinically significant relative to baseline from week 3 of treatment up to week 2 after treatment. Nadir was reached at week 6 of treatment for all scores, with maximum scores dropping by 15%, 20%, and 39% compared to baseline for FACT-G, FACT-Total, and FACT-TOI, respectively. Subdomain scores of physical well-being, functional well-being, and head and neck additional concerns decreased from baseline during treatment and returned to baseline at week 4 after treatment. Conclusions IMPT was associated with a favorable PRO trajectory, characterized by an acute decline followed by rapid recovery to baseline. This study establishes the expected acute, subacute, and chronic trajectory of PROs for patients undergoing IMPT for OPC.

BACKGROUND Guidelines for follow-up after head and neck cancer (HNC) treatment recommend frequent clinical examinations and surveillance testing. Here, the authors describe real-world follow-up care for HNC survivors and variations in surveillance testing. METHODS Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, this study examined a population-based cohort of HNC survivors between 2001 and 2011 Usage of cross-sectional head and neck imaging (CHNI), chest imaging (CI), positron emission tomography (PET), fiberoptic nasopharyngolaryngoscopy (FNPL), and, in irradiated patients, thyroid function testing (TFT) was captured over 2 consecutive surveillance years. Multivariate modeling with logistic regression analyses was used to assess variations by clinical factors, nonclinical factors, number and types of providers seen and their evolution over time. RESULTS Among 13,836 HNC survivors, the majority saw a medical, radiation, or surgical oncologist and a primary care provider (PCP; 81.7%) in their first year of surveillance. However, only 58.1% underwent either PET or CHNI, 47.8% underwent CHNI, 64.1% underwent CI, 32.5% underwent PET scans, 55.0% underwent FNPL, and 55.9% underwent TFT. In multivariate analyses, patients who followed up with more providers and those who followed up with both a PCP and an oncologist were more likely to undergo surveillance testing (P < .007). However, adjusting for providers seen did not explain the variations in surveillance testing rates based on age, race, education, income level, and place of residence. Over time, there was a gradual increase in the use of PET scans and TFT during surveillance years. CONCLUSIONS In this large SEER-Medicare data study, only half of HNC survivors received the recommended testing, and greater compliance was seen in those who followed up with both an oncologist and a PCP. More attention is needed to minimize variations in surveillance testing across sociodemographic groups.

Background This study aimed to evaluate the prognostic value of pre-treatment NLR in patients with oropharyngeal cancer. Methods Patients who completed definitive radiotherapy (RT) for oropharyngeal cancer and had blood counts taken pre-RT from 2002 to 2013 were included. NLR was calculated as total neutrophil/lymphocytes. Survival rates were estimated using the Kaplan–Meier method. Univariable and multivariable analyses were conducted with linear and Cox regression methods. NLR was analysed posteriori and dichotomised on the discovered median. Results Eight hundred and forty-eight patients were analysed. The median pre-RT NLR was 3. Patients with NLR of p p = 0.011; HPV-negative p = 0.003). Freedom from any recurrence (FFR), locoregional control (LRC) and freedom of distant recurrence (FDR) were better in those with NLR p = 0.001), FFR (HR = 1.6, p = 0.006) and LRC (HR = 1.8, p = 0.005) remained significant on multivariable analysis. Conclusions Pre-RT NLR is an independent prognostic factor in patients with oropharyngeal cancer regardless of HPV status. Patients with lower NLR had more favourable OS and disease control.

Background and purpose With an enlarging population of long-term oropharyngeal cancer survivors, dysphagia is an increasingly important toxicity following oropharynx cancer treatment. While lower doses to normal surrounding structures may be achieved with intensity modulated proton therapy (IMPT) compared to photon-based radiation, the clinical benefit is uncertain. Methods and materials Seventy-one patients with stage III/IV oropharyngeal cancer (AJCC 7th edition) undergoing definitive IMPT on a longitudinal prospective cohort study who had completed the MD Anderson Dysphagia Inventory (MDADI) at pre-specified time points were included. Results The majority of patients had HPV-positive tumors (85.9%) and received bilateral neck radiation (81.4%) with concurrent systemic therapy (61.8%). Mean composite MDADI scores decreased from 88.2 at baseline to 59.6 at treatment week 6, and then increased to 74.4 by follow up week 10, 77.0 by 6 months follow up, 80.5 by 12 months follow up, and 80.1 by 24 months follow up. At baseline, only 5.6% of patients recording a poor composite score (lower than 60), compared to 61.2% at treatment week 6, 19.1% at follow up week 10, 13.0% at 6 months follow up, 13.5% at 1 year follow up, and 11.1% at 2 years follow up. Conclusions Patient reported outcomes following IMPT for oropharyngeal cancer demonstrates decreased swallowing function at completion of treatment with relatively rapid recovery by 10 weeks follow up and steady improvement through 2 years. The results are comparable to similar longitudinal studies of photon-based radiotherapy for oropharynx cancer, and suggest that IMPT confers no additional excess toxicity related to swallowing.

Background Approximately one quarter of head and neck cancer (HNC) patients smoke cigarettes at the time of diagnosis. Despite HNC guideline recommendations to treat tobacco dependence, the effectiveness of treatment in this population is poorly described. Methods This retrospective cohort review evaluated 117 current smokers with p16-negative mucosal head and neck squamous cell carcinoma prospectively enrolled in a tobacco treatment program. Seven-day point prevalence tobacco abstinence rates at 9 months and survival outcomes were compared among abstinent and nonabstinent groups. Results Median follow-up among survivors was 62.4 months. Forty percent of patients were abstinent at 9 months according to intention-to-treat analysis. After adjustment for age, comorbidity and site, abstinent stage I to II patients had a decreased risk of death compared to smoking stage I to II patients (HR 0.15, 95% CI 0.03-0.82). Conclusions High cohort abstinence rates and favorable survival among abstinent patients with early-stage HNC confirm the importance of tobacco dependence treatment in this population.

Background Incidence of oropharyngeal cancer (OPC) is expected to increase but its health care cost is unknown. The purpose for this study was to estimate the phase-specific lifetime health care costs of OPC for commercially insured individuals in the United States. Methods We used the Truven MarketScan Commercial Claims and Encounter Database to identify our patient population. Cox survival analysis was used to estimate patients' monthly survival probabilities. We determined the ratios of the cumulative costs up to a particular survival probability and the costs from that time point to death for all subjects who died before end of the 5-year follow-up period. This relationship was then used to predict phase-specific lifetime health care costs. Results Our study included 2445 patients with OPC. The predicted phase-specific lifetime health care costs attributable to OPC were $88 872, $24 038, and $1537 in the initial, continuous, and terminal phases, respectively, among commercially insured patients.

Background In the face of the COVID‐19 pandemic, cancer care has had to adapt rapidly given the Centers for Disease Control and Prevention and the American College of Surgeons (ACS) issuing recommendations to postpone nonurgent surgeries. Methods An institutional multidisciplinary group of Head and Neck Surgical Oncology, Surgical Endocrinology, and Medical Endocrinology devised Surgical Triaging Guidelines for Endocrine Surgery during COVID‐19, aligned with phases of care published by the ACS. Results Phases of care with examples of corresponding endocrine cases are outlined. Most cases can be safely postponed with active surveillance, including most differentiated and medullary thyroid cancers. During the most acute phase, all endocrine surgeries are deferred, except thyroid tumors requiring acute airway management. Conclusions These guidelines provide context for endocrine surgery within the spectrum of surgical oncology, with the goal of optimal individualized multidisciplinary patient care and the expectation of significant resource diversion to care for patients with COVID‐19.

IMPORTANCE: Surveillance imaging and visits are costly and have not been shown to improve oncologic outcomes for patients with head and neck cancer (HNC). However, the benefit of surveillance visits may extend beyond recurrence detection. To better understand surveillance and potentially develop protocols to tailor current surveillance paradigms, it is important to elicit the perspectives of the clinicians who care for patients with HNC. OBJECTIVE: To characterize current surveillance practices and explore clinician attitudes and beliefs on deintensifying surveillance for patients with HNC. DESIGN, SETTING, AND PARTICIPANTS: This qualitative study was performed from January to March 2021. Guided by an interpretive description approach, interviews were analyzed to produce a thematic description. Data analysis was performed from March to April 2021. Otolaryngologists and radiation oncologists were recruited using purposive and snowball sampling strategies. MAIN OUTCOMES AND MEASURES: The main outcomes were current practice, attitudes, and beliefs about deintensifying surveillance and survivorship as well as patients’ values and perspectives collected from interviews of participating physicians. RESULTS: Twenty-one physicians (17 [81%] men) were interviewed, including 13 otolaryngologists and 8 radiation oncologists with a median of 8 years (IQR, 5-20 years) in practice. Twelve participants (57%) stated their practice comprised more than 75% of patients with HNC. Participants expressed that there was substantial variation in the interpretation of the surveillance guidelines. Participants were open to the potential for deintensification of surveillance or incorporating symptom-based surveillance protocols but had concerns that deintensification may increase patient anxiety and shift some of the burden of recurrence monitoring to patients. Patient and physician peace of mind, the importance of maintaining the patient-physician relationship, and the need for adequate survivorship and management of treatment-associated toxic effects were reported to be important barriers to deintensifying surveillance. CONCLUSIONS AND RELEVANCE: In this qualitative study, clinicians revealed a willingness to consider altering cancer surveillance but expressed a need to maintain patient and clinician peace of mind, maintain the patient-clinician relationship, and ensure adequate monitoring of treatment-associated toxic effects and other survivorship concerns. These findings may be useful in future research on the management of posttreatment surveillance.

It is estimated that 5% of the global cancer burden, or approximately 690,000 cancer cases annually, is attributable to human papillomavirus (HPV). Primary prevention through prophylactic vaccination is the best option for reducing the burden of HPV-related cancers. Most high-income countries (HICs) have introduced the HPV vaccine and are routinely vaccinating adolescent boys and girls. Unfortunately, although they suffer the greatest morbidity and mortality due to HPV-related cancers, many lower- and middle-income countries (LMICs) have been unable to initiate and sustain vaccination programs. Secondary prevention in the form of screening has led to substantial declines in cervical cancer incidence in areas with established screening programs, but LMICs with absent or inadequate screening programs have high incidence rates. Meanwhile, HICs have seen incidence rates of anal and oropharyngeal cancers rise owing to the limited availability of organized screening for anal cancer and no validated screening options for oropharyngeal cancer. The implementation of screening programs for individuals at high risk of these cancers has the potential to reduce the burden of cervical cancer in LMICs, of anal and oropharyngeal cancers in HICs, and of anal cancer for highly selected HIV positive populations in LMICs. This review will discuss primary prevention of HPV-related cancers through vaccination and secondary prevention through screening of cervical, anal, and oropharyngeal cancers. Areas of concern and highlights of successes already achieved are included.

PURPOSE: We report longitudinal patient-reported quality-of-life (QoL) outcomes related to xerostomia in patients with oropharyngeal cancer treated with intensity-modulated proton therapy (IMPT). MATERIALS AND METHODS: Patients treated from May 2012 through December 2016 at a single institution for AJCC7 stage III-IV, M0 oropharyngeal cancer were given the 15-item Xerostomia-Related QoL Scale (XeQoLS) before, during, and for up to 2 years after treatment. We evaluated the evolution of xerostomia-related QoL over that time, and examined potential associations between those measures with clinical characteristics. RESULTS: Sixty-nine patients had XeQoLS scores at baseline and at least once either during or after treatment. The mean (±SD) XeQoLS score (0–4) was 0.24 ± 0.57 at baseline. Subsequent scores were 2.00 ± 1.01 at 6 weeks on treatment, and 1.03 ± 0.76, 0.97 ± 0.78, 0.82 ± 0.69, and 0.70 ± 0.75 at 10 weeks, 6 months, 1 year, and 2 years after treatment, respectively. All were statistically different from baseline (p < 0.001). Univariate analyses demonstrated associations between XeQoLS score and time (p < 0.0001 for each interval), baseline XeQoLS score (p < 0.0001), stage (p = 0.008), N status (p = 0.006), and mean oral cavity dose (p = 0.038), but not for age, sex, T status, receipt of chemotherapy, smoking history, disease site, laterality of neck irradiation, mean parotid dose, or mean submandibular dose. Multivariate analysis suggested that baseline XeQoLS scores, phase of treatment, and N status were associated with XeQoLS scores measured during treatment and recovery. CONCLUSIONS: Patients receiving IMPT reported the greatest xerostomia-related QoL impairment at 6 weeks on treatment, with a 49% improvement by 10 weeks after treatment; however, XeQoLS scores remained above baseline after 2 years. As we aim to establish the value of IMPT in oropharyngeal tumors to de-intensify treatment over conventional therapy, these data help inform discussions about xerostomia-related quality of life for patients with oropharyngeal cancer treated with IMPT.

Chronic hepatitis C virus (HCV) infection increases the risk for several types of cancer, including hepatocellular carcinoma (HCC) and B-cell non-Hodgkin lymphoma, as primary and second primary malignancies. HCV-infected patients with cancer, particularly those undergoing anticancer therapy, are at risk for development of enhanced HCV replication, which can lead to hepatitis flare and progression of liver fibrosis or cirrhosis. Risk factors for HCV infection include injection drug use, blood transfusion, or solid organ transplantation before 1992, receipt of clotting factor concentrates before 1987, long-term hemodialysis, chronic liver disease, HIV positivity, and occupational exposure. Widely available direct-acting antivirals are highly effective against HCV and well tolerated. Identification of HCV-infected individuals is the essential first step in treatment and eradication of the infection. One-time screening is recommended for persons born from 1945 to 1965; screening is also recommended for persons with risk factors. Recently, a public health recommendation has been drafted to screen all adults age 18 to 79 years. Two oncology organizations recommend screening all patients with hematologic malignancies and hematopoietic cell transplant recipients, and a recently published multicenter prospective study supports universal HCV screening for all patients with cancer. HCV screening entails testing for anti-HCV antibodies in serum and, when results are positive, HCV RNA quantitation to confirm infection. Direct-acting antiviral therapy eradicates HCV in almost all cases. Virologic cure of HCV prevents chronic hepatitis and progression to liver fibrosis or cirrhosis. HCV eradication also decreases the risk of developing HCV-associated primary and second primary malignancies, and it may allow HCV-infected patients access to important cancer clinical trials. Patients with HCV-related cirrhosis require lifelong surveillance for HCC, even after viral eradication.

Objectives Oropharyngeal squamous cell carcinoma (OPSCC) incidence is rapidly increasing in the United States and around the world, driven in large part by infection with the human papillomavirus (HPV). HPV associated OPSCC (HPV+OPSCC) has been shown to have improved response to treatment relative to tobacco-associated OPSCC. However, improvement in patient survival has not been uniform. Subsets of OPSCC patients in the US and around the world continue to have poor oncologic outcomes. Although the drivers of this phenomenon remain unclear, there is increasing evidence that tobacco exposure plays an important role in modulating HPV+OPSCC clinical outcomes. Methods We conducted a review of the literature. Results We discuss the potential biological and epidemiological interplay between tobacco and HPV exposure in the context of OPSCC. Multiple retrospective and prospective cohorts show that HPV+OPSCC patients with a history of tobacco exposure have response to treatment and clinical outcomes distinct from HPV+OPSCC non-smokers which poses clinical and scientific challenges to be addressed over the next decade. Conclusions The interaction between tobacco exposure and HPV infection in the context of OPSCC has significant implications for both standard of care treatment regimens and development of novel therapeutic approaches, in particular those which incorporate immunomodulatory agents. Level of evidence 5.

Hypoparathyroidism occurs relatively frequently after thyroid surgery in children. However, few studies have reported risk factors. We aimed to identify risk factors for hypoparathyroidism that occurred after total thyroidectomy for proven or suspected malignancy in children. Children (aged ≤ 18 years) who underwent total thyroidectomy for neoplasm or RET germline mutation at our institution between 1997 and 2018 were included. We retrospectively reviewed demographics, surgical indications, perioperative and follow-up laboratory results, pathologic results, and duration of calcium/calcitriol supplementation. Risk factors for hypoparathyroidism were identified by multivariate analysis. Of 184 consecutive patients, 111 had undergone surgery for neoplasm; these diseases were primarily malignancies (106, 95.5%), predominantly papillary carcinoma (103, 92.8%). The remaining 73 patients had undergone early thyroidectomy for RET germline mutation. Among all patients, 67 (36.4%) had hypoparathyroidism: 61 transient and 6 permanent. In a multivariate analysis, central neck dissection (odds ratio 4.3, 95% confidence interval 2.0–9.1) and gross extrathyroidal extension (odds ratio 4.9, 95% confidence interval 2.0–12.1) predicted overall hypoparathyroidism; however, no significant factors were associated with permanent hypoparathyroidism. Most patients with permanent hypoparathyroidism (5 of 6) had undergone therapeutic central neck dissection. When central neck dissection was performed, younger children had a higher risk of overall hypoparathyroidism. In pediatric total thyroidectomies, central neck dissection and gross extrathyroidal extension were major predictors for overall hypoparathyroidism. Surgeons performing thyroidectomy in such patients should be aware of the relatively high risk, preserve parathyroid tissue to the extent possible, and be conscientious regarding postoperative calcium monitoring and replacement.

Objectives The aim of this study was to estimate the direct 2-year mean incremental medical care costs for incident oropharyngeal cancer (OPC) from the perspective of the Texas Medicaid program. Methods OPC patients treated from 2008 to 2012 were selected in the Texas Medicaid database. Using a two-step 1:1 propensity score matching method, we selected controls to determine the differential cost associated with OPC. Monthly and yearly direct costs were estimated for 2 years after the cancer diagnosis. For patients without 2-year complete follow-up, a generalized linear model with gamma distribution and log link function was applied to predict costs for the censored months. Results A total of 352 patients with OPC and the same number of controls were included in the study. Among OPC patients, 204 (58%) were covered by Medicaid and Medicare, and 148 patients (42%) were insured under Medicaid only. The adjusted first- and second-year mean differential costs were $45,102 and $11,684 for Medicaid-only enrollees and $5734 and $2162 for Medicaid-Medicare dual-eligible enrollees, respectively. Being male, Hispanic, Medicaid-only eligible, living in the Harlingen region, and having more comorbidities were positively associated with monthly cost. Lubbock residents experienced lower costs. Conclusions The direct incremental medical costs associated with OPCs among patients insured by Texas Medicaid were substantial in the first 2 years after cancer diagnosis and should be considered in assessing the economic consequences of increasing the investment in HPV vaccination in Texas.

Second primary malignancy (SPM) may occur after index head and neck cancer (HNC) treatment. This study evaluated the prevalence and outcome of SPM in patients with HNC treated with definitive radiotherapy. Eligible patients include those with index mucosal HNC treated with definitive radiotherapy between 2000 and 2010. SPM was defined as an invasive cancer at a noncontiguous site diagnosed at least 6 months after completion of radiotherapy. Clinical data were collected, and the Kaplan–Meier method was used to estimate overall survival. In total, 1512 patients were studied. The majority of patients had index oropharyngeal cancer (86%). In all, 130 (9%) patients developed a SPM. The risk of SPM increased exponentially with time with 5-, 10-, and 15-year rates of 4, 10, and 25%. Half of SPMs were within the head and neck or thoracic regions. SPM rates were significantly higher (p

Background: When achieved, complete surgical resection improves outcomes in anaplastic thyroid carcinoma (ATC). However, most ATC patients present with advanced inoperable disease, often with impending airway obstruction, increased hemorrhage risk, and significant dysphagia. Novel treatment strategies are critically needed to improve disease control and decrease locoregional morbidity. The objective of this study was to determine the feasibility and effectiveness of a neoadjuvant regimen by using dabrafenib with trametinib followed by surgical resection in patients with initially unresectable BRAFV600E-mutated ATC. Methods: Case series of six consecutive patients with BRAFV600E-mutated ATC diagnosed between January 2017 and February 2018. Pathologic confirmation of ATC was obtained before treatment. BRAFV600E status was ascertained via immunohistochemistry or sequencing of circulating tumor DNA. All patients received dabrafenib and trametinib (DT) followed by surgical resection and adjuvant chemoradiation. Three patients also received pembrolizumab. Results: Complete surgical resection was achieved in all patients. Histopathologic analyses of resected specimens showed high pathologic response rates with significantly decreased ATC viability and residual papillary thyroid carcinoma components. Overall survival at six months and one year was 100% and 83%, respectively. Locoregional control rate was 100%. Two patients died of distant metastases without evidence of locoregional disease at 8 and 14 months from diagnosis. The remaining four patients had no evidence of disease at the last follow-up. Conclusions: We report the first series in the literature of BRAFV600E-mutated ATC patients with locoregionally advanced disease treated with DT followed by surgical resection. We demonstrated feasibility of complete resection, decreased need for tracheostomy, high pathologic response rates, and durable locoregional control with symptom amelioration.

Objective To estimate the prevalence of high-grade anal dysplasia in women with high-grade dysplasia or carcinoma of the cervix, vagina or vulva. Methods In this cross-sectional study, participants underwent anal cytology, anal HPV testing with Cervista HPV16/18 and high-resolution anoscopy (HRA). Patients with HSIL (high-grade squamous cell intraepithelial lesion) or greater on anal cytology or anal biopsy were referred to a colorectal surgery specialist for further evaluation. Results Seventy-five women were enrolled in the study, including 47 with cervical (cervix group), 10 with vaginal (vagina group), 15 with vulvar (vulva group), 1 with cervical and vaginal, and 2 with vulvar and vaginal disease. The median age in the cervix group (40 years (range 26–69)) was substantially younger than in the vagina (60 years (38–69)) and the vulva (59 years (36–75)) groups. Anal HSIL based on composite endpoints of the most severe cytology or histology result was diagnosed in 6 patients (8.0%). Anal cytology revealed HSIL in 2 (2.7%), atypical squamous cells of undetermined significance (ASCUS) in 12 (16.0%), low-grade squamous cell intraepithelial lesion (LSIL) in 2 (2.7%), and was normal in 59 (78.7%) patients. Anal HPV16/18 test was positive in 15 (20.0%), negative in 48 (64.0%) and insufficient in 12 (16.0%) patients. Of the 6 women with high-grade anal dysplasia, three (50%) had a positive anal HPV16/18 test. No case of anal cancer was observed. Conclusion Our results suggest that the prevalence of anal HSIL is elevated among women with HPV-related lower genital tract dysplasia or cancer. To further support the inclusion of this high-risk group into screening guidelines for anal dysplasia, further studies are necessary to determine what screening strategy is suited to this population.

Background This study was conducted to identify clinicodemographic risk factors for xerostomia among long-term oropharyngeal cancer (OPC) survivors. Methods This cross-sectional study included 906 disease-free, adult OPC survivors with a median survival duration at the time of survey of 6 years (range, 1-16 years); self-reported xerostomia scores were available for 877 participants. Study participants had completed curative treatment between January 2000 and December 2013 and responded to a survey administered from September 2015 to July 2016. The primary outcome variable was cancer patient-reported xerostomia measured with the MD Anderson Symptom Inventory Head and Neck Cancer Module. Clinicodemographic risk factors for moderate to severe xerostomia were identified via multivariable logistic regression. Results Moderate to severe xerostomia was reported by 343 of the respondents (39.1%). Female sex (odds ratio [OR], 1.82; 95% CI, 1.22-2.71; P = .003; Bayesian false-discovery probability [BFDP] = 0.568), high school or lower education (OR, 1.73; 95% CI, 1.19-2.52; P = .004; BFDP = 0.636), and current cigarette smoking at the time of survey (OR, 2.56; 95% CI, 1.19-5.47; P = .016; BFDP = 0.800) were risk factors for moderate to severe xerostomia, and bilateral intensity-modulated radiotherapy (IMRT) combined with proton therapy and ipsilateral IMRT were protective. Conclusions In this large xerostomia study, modern radiotherapy was a protective factor, and continued cigarette smoking at the time of survey, female sex, and high school or lower education were identified as other contributing risk factors associated with moderate to severe xerostomia. Importantly, these findings need to be confirmed in prospective studies. These results can inform future research and targeted patient-centered interventions to monitor and manage radiation therapy-associated xerostomia and preserve quality of life among patients with OPC.

In 2017, 46,157 and 3,127 new oropharyngeal cancer (OPC) cases were reported in the U.S. and Texas, respectively. About 70% of OPC were attributed to human papillomavirus (HPV). However, only 51% of U.S. and 43.5% of Texas adolescents have completed the HPV vaccine series. Therefore, modeling the demographic dynamics and transmission of HPV and OPC progression is needed for accurate estimation of the economic and epidemiological impacts of HPV vaccine in a geographic area. An age-structured population dynamic model was developed for the U.S. state of Texas. With Texas-specific model parameters calibrated, this model described the dynamics of HPV-associated OPC in Texas. Parameters for the Year 2010 were used as the initial values, and the prediction for Year 2012 was compared with the real age-specific incidence rates in 23 age groups for model validation. The validated model was applied to predict 100-year age-adjusted incidence rates. The public health benefits of HPV vaccine uptake were evaluated by computer simulation. Compared with current vaccination program, increasing vaccine uptake rates by 50% would decrease the cumulative cases by 4403, within 100 years. The incremental cost-effectiveness ratio of this strategy was $94,518 per quality-adjusted life year (QALY) gained. Increasing the vaccine uptake rate by 50% can: (i) reduce the incidence rates of OPC among both males and females; (ii) improve the quality-adjusted life years for both males and females; (iii) be cost-effective and has the potential to provide tremendous public health benefits in Texas.

Background Despite the significant societal burden of human papillomavirus (HPV)-associated cancers, clinical screening interventions for HPV-associated noncervical cancers are not available. Blood-based biomarkers may help close this gap in care. Methods Five databases were searched, 5687 articles were identified, and 3631 unique candidate titles and abstracts were independently reviewed by 2 authors; 702 articles underwent a full-text review. Eligibility criteria included the assessment of a blood-based biomarker within a cohort or case-control study. Results One hundred thirty-seven studies were included. Among all biomarkers assessed, HPV-16 E seropositivity and circulating HPV DNA were most significantly correlated with HPV-associated cancers in comparison with cancer-free controls. In most scenarios, HPV-16 E6 seropositivity varied nonsignificantly according to tumor type, specimen collection timing, and anatomic site (crude odds ratio [cOR] for p16+ or HPV+ oropharyngeal cancer [OPC], 133.10; 95% confidence interval [CI], 59.40-298.21; cOR for HPV-unspecified OPC, 25.41; 95% CI, 8.71-74.06; cOR for prediagnostic HPV-unspecified OPC, 59.00; 95% CI, 15.39-226.25; cOR for HPV-unspecified cervical cancer, 12.05; 95% CI, 3.23-44.97; cOR for HPV-unspecified anal cancer, 73.60; 95% CI, 19.68-275.33; cOR for HPV-unspecified penile cancer, 16.25; 95% CI, 2.83-93.48). Circulating HPV-16 DNA was a valid biomarker for cervical cancer (cOR, 15.72; 95% CI, 3.41-72.57). In 3 cervical cancer case-control studies, cases exhibited unique microRNA expression profiles in comparison with controls. Other assessed biomarker candidates were not valid. Conclusions HPV-16 E6 antibodies and circulating HPV-16 DNA are the most robustly analyzed and most promising blood-based biomarkers for HPV-associated cancers to date. Comparative validity analyses are warranted. Variations in tumor type-specific, high-risk HPV DNA prevalence according to anatomic site and world region highlight the need for biomarkers targeting more high-risk HPV types. Further investigation of blood-based microRNA expression profiling appears indicated.

Background Risk of recurrence among patients with oropharyngeal cancer (OPC) who survive 5 years is low. The goal of this study was to assess long-term survival of patients with OPC alive without recurrence 5 years after diagnosis. Methods This study included newly diagnosed patients with OPC, who had been treated with radiation and were alive without recurrence 5 years after diagnosis. Overall survival (OS) probabilities beyond 5 years were estimated using the Kaplan-Meier method. Factors associated with OS were determined using Bayesian piecewise exponential survival regression. Standardized mortality ratios for all-cause death were estimated controlling for study year, age, and sex in the US general population. Results Among 1699 patients, the additional 2-year, 5-year, and 10-year OS probabilities were 94%, 83%, and 63%, respectively, and were lower than those in the general population. Patients who were older, were current or former smokers, had other than tonsil or base of tongue tumors, or had T4 tumors had a higher risk of death. Patients who had base of tongue tumors and had received intensity-modulated radiation therapy (IMRT) or lower-radiation doses had a lower risk of death. Standardized mortality ratios were higher among current and heavy smokers and lower among recipients of IMRT and lower radiation doses. Conclusions In this large cohort, long-term survival among patients with OPC was good but lower than predicted for the general population. Patients treated with IMRT and those with less tobacco exposure had better outcomes.

To characterize pharyngocutaneous fistula (PCF) rates and functional outcomes following microvascular free tissue transfer (MVFTT) reconstruction of salvage total laryngectomy (STL) with a review of two different flap inset techniques and a review of the literature.Retrospective review.Review of the literature revealed 887 patients who underwent STL MVFTT from 14 references. Ninety-six STL MVFTTs were performed by the authors, with 36 (38%) patients undergoing multilayer fascial underlay (MLFU) closure and 60 (62%) a standard single layer closure (SLC). One (3%) PCF occurred in the MLFU group compared to 12 (20%) in the SLC cohort (P = .03). Postoperative gastrostomy (G)-tube dependence was lower following MLFU closure compared to SLC (25% vs. 57%, P .01), whereas pharyngoesophageal stricture (PES) (28% vs. 38%), tracheoesophageal puncture (TEP) placement (42% vs. 42%), and TEP usage (87% vs. 88%) did not significantly differ (P .05). Compared to pooled rates from the literature, patients who underwent a MLFU MVFTT inset technique demonstrated significantly lower PCF incidence (3% vs. 23%, P .01) without significant differences in PES (28% vs 23%, P = .55), G-tube dependence (25% vs. 23%, P = .25), or TEP placement (42% vs. 59%, P = .09).Despite MVFTT reconstruction after STL, G-tube dependence, PCF formation, and limitations of speaking rehabilitation (TEP) remain a significant issue. Modification of MVFTT inset may provide an opportunity to reduce PCF incidence without affecting other functional outcomes.4 Laryngoscope, 131:E875-E881, 2021.

Background The current study was performed to assess the efficacy of surveillance imaging in patients with head and neck cancer (HNC) who are treated definitively with radiotherapy. Methods Eligible patients included those with a demonstrable disease-free interval (≥1 follow-up imaging procedure without evidence of disease and a subsequent visit/imaging procedure) who underwent treatment of HNC from 2000 through 2010. Results A total of 1508 patients were included. The median overall survival was 99 months, with a median imaging follow-up period of 59 months. Of the 1508 patients, 190 patients (12.6%) experienced disease recurrence (107 patients had locoregional and 83 had distant disease recurrence). A total of 119 patients (62.6%) in the group with disease recurrence were symptomatic and/or had an adverse clinical finding associated with the recurrence. Approximately 80% of patients with locoregional disease recurrences presented with a clinical finding, whereas 60% of distant disease recurrences were detected by imaging in asymptomatic patients. Despite the earlier detection of disease recurrence via imaging, those patients in the group of patients with clinically detected disease recurrence were significantly more likely to undergo salvage therapy compared with those whose recurrence was detected on imaging (odds ratio, 0.35). There was no difference in overall survival noted between those patients with disease recurrences that were detected clinically or with imaging alone. Approximately 70% of disease recurrences occurred within the first 2 years. In those patients who developed disease recurrence after 2 years, the median time to recurrence was 51 months. After 2 years, the average number of imaging procedures per patient for the detection of a salvageable recurrence for the imaging-detected group was 1539. Conclusions Surveillance imaging in asymptomatic patients with HNC who are treated definitively with radiotherapy without clinically suspicious findings beyond 2 years has a low yield and a high cost. Physicians ordering these studies must use judicious consideration and discretion.

Because lymphocyte telomere length (LTL) plays critical roles in the maintenance of genomic stability and integrity, LTL thus may influence the etiology and prognosis of squamous cell carcinoma of the oropharynx (SCCOP). However, given the association between LTL and risk of human papillomavirus (HPV)-associated SCCOP and between LTL and tumor HPV status of SCCOP, we hypothesized that LTL is associated with SCCOP prognosis, particularly in HPV-positive patients after definitive radiotherapy. LTL and tumor HPV type 16 (HPV16) status were determined in 564 incident SCCOP patients before radiotherapy or chemoradiation. Both univariate and multivariable Cox regression analyses were performed to estimate the association between LTL and prognosis. Eighty-five percent patients had HPV16-positive tumors. Patients with shorter telomeres had significantly better overall, disease-specific and disease-free survival than did those with longer telomeres (log-rank P < 0.001). Moreover, patients with shorter telomeres had significantly lower risk of death overall [hazard ratio (HR) = 0.2; 95% confidence interval (CI) = 0.1–0.4], death due to SCCOP (HR = 0.2; 95% CI = 0.1–0.4) and SCCOP recurrence (HR = 0.3; 95% CI = 0.2–0.5) after adjusting for other important prognostic confounders. Finally, we found more pronounced effects of LTL on survival in HPV16-positive SCCOP patients after stratified analysis according to tumor HPV status. These findings indicate that LTL plays a significant role in the survival of patients with SCCOP, especially HPV16-positive patients who undergo definitive radiotherapy. Therefore, pretreatment LTL may be an independent prognostic biomarker for HPV16-positive SCCOP. Prospective studies with larger sample sizes are needed to confirm these findings.

Highlights • For 40 years, all soft tissue sarcoma (STS) used the same TNM where T1 was 5 cm. • Despite smaller size, local recurrence is higher in STSHN compared to other STS. • A new T classification with 2 and 4 cm cut-offs for STSHN was introduced in TNM-8. • Future requirements for STSHN Stage Group development are mentioned., The tumor, node, metastases (TNM) anatomic staging system plays a pivotal role in cancer care, research, and cancer control activities. Since the first edition of the American Joint Committee on Cancer TNM staging classification published in 1977, soft tissue sarcomas have been staged in an anatomic site agnostic fashion whereby the primary tumor size (T) was categorized as T1 if 5 cm; this remained unchanged through the 7th edition of the TNM. However, soft tissue sarcomas of the head and neck (STSHN) usually present smaller than sarcomas of other sites, but carry a disproportionate risk of local recurrence. Up to 70% of tumors are less than 5 cm at presentation, and therefore classified together as T1. Given the rarity of STSHN, there is a paucity of data to guide progress in their classification. Moreover, the majority of publications only report tumor size as less than or greater than 5 cm, presumably based on conventions of the TNM system that remained unchanged for 40 years, thereby affecting progress of STSHN classification. This formed the impetus for change in the 8th edition in 2 key ways: 1) several soft tissue sarcoma site based changes occurred including STSHN now having its own system, and 2) primary tumor size cut-offs of 2 cm and 4 cm used in STSHN now reflect sizes that head and neck specialists commonly encounter in their practice. This update was pragmatic in modifying the TNM from a system with a T category not serving STSHN and which was originally based on sarcoma data from non-head and neck anatomic sites. The background to this change is outlined which provides a framework in which data can be reported to generate evidence for future staging modifications.

BACKGROUND: The objective of the current study was to characterize the incidence, pattern, and impact on oncologic outcomes of retropharyngeal lymph node (RPLN) involvement in HPV-associated oropharyngeal cancer (OPC). METHODS: Data regarding patients with HPV-associated OPC who were treated at The University of Texas MD Anderson Cancer Center with intensity-modulated radiotherapy from 2004 through 2013 were analyzed retrospectively. RPLN status was determined by reviewing pretreatment imaging and/or reports. Outcomes analysis was restricted to patients with lymph node-positive (+) disease. Kaplan-Meier survival estimates were generated and survival curves were compared using the log-rank test. Bayesian information criterion assessed model performance changes with the addition of RPLN status to current American Joint Committee on Cancer staging. Competing risk analysis compared modes of disease recurrence. RESULTS: The incidence of radiographic RPLN involvement was 9% (73 of 796 patients) and was found to vary by primary tumor site. The 5-year rates of freedom from distant metastases (FDM) and overall survival were lower in patients with RPLN(+) status compared with those with RPLN-negative (−) status (84% vs 93% [P = .0327] and 74% vs 87% [P = .0078], respectively). RPLN(+) status was not found to be associated with outcomes on multivariate analysis. Bayesian information criterion analysis demonstrated that current American Joint Committee on Cancer staging was not improved with the inclusion of RPLN. Locoregional and distant disease recurrence probabilities for those patients with RPLN(+) status were 8% and 13%, respectively, compared with 10% and 6%, respectively, for those with RPLN(−) status. RPLN(+) status portended worse 5-year FDM in the low-risk subgroup (smoking history of

BACKGROUND. Optimal hepatitis C virus (HCV) screening strategies for cancer patients have not been established. We compared the performance of selective HCV screening strategies. METHODS. We surveyed patients presenting for first systemic anticancer therapy during 2013–2014 for HCV risk factors. We estimated the prevalence of positivity for HCV antibody (anti-HCV) and examined factors associated with anti-HCV status using Fisher’s exact test or Student’s t-test. Sensitivity was calculated for screening patients born during 1945–1965, patients with ≥1 other risk factor, or both cohorts (“combined screening”). RESULTS. We enrolled 2,122 participants. Median age was 59 years (range, 18–91); 1,138 participants were women. Race/ethnicity distribution was white non-Hispanic, 76% (n=1616); Hispanic, 11% (n=233); black non-Hispanic, 8% (n=160); Asian, 4% (n=78); other, 2% (n=35). Primary cancer distribution was non-liver solid tumor, 78% (n=1,664); hematologic cancer, 20% (n=422); liver cancer, 1% (n=28). Prevalence of anti-HCV was 1.93% (95% CI, 1.39%–2.61%). Over 28% of patients with detectable HCV RNA were unaware of infection. Factors significantly associated with anti-HCV positivity included less than a bachelor’s degree, birth in 1945–1965, chronic liver disease, injection drug use, and blood transfusion or organ transplant before 1992. A total of 1,315 participants (62%), including 39 of 41 with anti-HCV, reported ≥1 risk factor. Sensitivity was 80% (95% CI, 65–91%) for birth-cohort-based, 68% (95% CI, 52–82%) for other-risk-factor-based, and 95% (95% 83–99%) for combined screening. CONCLUSION. Combined screening still missed 5% of patients with anti-HCV. These findings favor universal HCV screening to identify all HCV-infected cancer patients.

Head and neck cancer (HNC) risk prediction models based on risk factor profiles have not yet been developed. We took advantage of the large database of the International Head and Neck Cancer Epidemiology (INHANCE) Consortium, including 14 US studies from 1981–2010, to develop HNC risk prediction models. Seventy percent of the data were used to develop the risk prediction models; the remaining 30% were used to validate the models. We used competing-risk models to calculate absolute risks. The predictors included age, sex, education, race/ethnicity, alcohol drinking intensity, cigarette smoking duration and intensity, and/or family history of HNC. The 20-year absolute risk of HNC was 7.61% for a 60-year-old woman who smoked more than 20 cigarettes per day for over 20 years, consumed 3 or more alcoholic drinks per day, was a high school graduate, had a family history of HNC, and was non-Hispanic white. The 20-year risk for men with a similar profile was 6.85%. The absolute risks of oropharyngeal and hypopharyngeal cancers were generally lower than those of oral cavity and laryngeal cancers. Statistics for the area under the receiver operating characteristic curve (AUC) were 0.70 or higher, except for oropharyngeal cancer in men. This HNC risk prediction model may be useful in promoting healthier behaviors such as smoking cessation or in aiding persons with a family history of HNC to evaluate their risks.

Purpose Patients with p16/human papilloma virus (HPV)–associated oropharyngeal squamous cell carcinoma have a favorable outcome after treatment. In this group of patients who could have a long life expectancy, the optimal surveillance strategy and modality is not well established. We aim to determine the ability of a negative postradiation positron emission tomography (PET)/computed tomography scan to predict the risk of subsequent relapse in these patients. Materials and Methods A retrospective analysis of patients with p16/HPV-associated oropharyngeal squamous cell carcinoma who completed definitive (chemo)radiation therapy and had a posttreatment PET/computed tomography scan from 2006 to 2013 was performed. Patient, tumor, and treatment characteristics and clinical outcomes were recorded. Tumors were considered HPV/p16 positive if either HPV (by in situ hybridization) or p16 (by immunohistochemistry) was positive. Disease-free survival and overall survival rates were estimated using the Kaplan-Meier method. Results In our study, 327 patients were evaluated. The median age was 57 years. The most common primary sites were base of tongue (50%) and tonsil (48%). Of the patients evaluated, 291 (89%) had a negative posttreatment PET scan. For these 291 patients who had a complete metabolic response after treatment, the 5-year disease-free survival and overall survival rates were 91% and 89%, respectively. The median time to development of recurrence was 16 months. Of the 291 patients, 24 patients (8%) had disease recurrence; 13 recurrences were locoregional, and 13 were distant. Eleven (4%) patients with recurrence had further surgery or radiation, and 8 patients (3%) were without disease as of the last follow-up. Conclusions Patients who achieve a complete metabolic response on posttreatment PET imaging have an excellent prognosis, and the risk of developing a recurrence in the future is very low. Therefore, a more cost effective surveillance program should be considered for this subgroup of patients.

The American Joint Committee on Cancer Cancer Staging System for differentiated thyroid cancer has been recently revised. The purpose of this study was to compare survival prognostication between the seventh and eighth editions.We retrospectively reviewed 2579 differentiated thyroid cancer patients who underwent surgery at MD Anderson Cancer Center between 2000 and 2015. Disease-specific survival (DSS) and overall survival were estimated using the Kaplan-Meier method and compared using log rank test. The effect of potential predictor was estimated using Cox proportional hazards model. Power of survival prediction was estimated using Harrell's C concordance index (C-index), and predictive capacities for DSS were estimated using proportion of variance explained (PVE).Revision of tumor-node-metastasis (TNM) categories, age cutoff, and stage reassignment in the 8The AJCC eighth edition is similar to the seventh edition in disease-specific survival prediction. Potential modifications that may improve disease-specific survival prediction in future renditions include reconsideration of T3b tumor category and upstaging classification of patients55 years of age with distant metastases.

Risk-stratified treatment strategies have become a focus in the treatment of differentiated thyroid cancer (DTC). In the 2015 American Thyroid Association treatment guidelines, adjuvant treatment with radioactive iodine (RAI) is considered in the presence of minimal extrathyroidal extension (mETE). This study aimed to investigate the prognostic significance of mETE and tumor size in patients with DTC.A retrospective review was undertaken of 2323 consecutive patients treated surgically for T1-T3 (defined per seventh edition of the American Joint Committee on Cancer staging criteria) and M0 DTC from 2000 to 2015 at The University of Texas MD Anderson Cancer Center. Patients were divided into four groups according to the size of the tumor (≤4 cm vs.4 cm) and the presence of mETE. Predictors of disease-free survival (DFS), disease-specific survival, locoregional failure (LRF), and distant metastatic failure (DMF) were compared using the log-rank test and Cox's proportional hazards models.There were only seven DTC-related deaths, limiting the clinical significance of the analysis, especially of overall and disease-specific survival. Following multivariate analysis, patients with tumors4 cm did worse than patients with tumors ≤4 cm with respect to DFS (group 3 [4 cm without mETE] adjusted hazard ratio (HRTumor size, but not the presence of mETE, was an independent predictor of DFS, LRF, and DMF in DTC.

Perivascular epithelioid cell tumors (PEComas) in the head and neck region are rare, with 26 cases described in literature. These distinct mesenchymal tumors normally express both myoid and melanocytic markers. We here report an interesting and challenging case of malignant PEComa that showed transcription factor E3 (TFE3) protein expression and rearrangement, paucity of muscle and melanocytic marker expression, and morphologically mimicked alveolar soft part sarcoma. Awareness of this morphologic pitfall and recognition of TFE3 gene-rearranged PEComa, as a distinct subtype of PEComa, is essential to avoid misdiagnosis.

The incidence rate of hepatocellular carcinoma (HCC) is rising. It is one of the most common cancers worldwide and accounts for substantial morbidity and mortality. Chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, and nonalcoholic fatty liver disease (NAFLD) are the most important etiologies of HCC, and effective screening and management strategies are crucial to reduce the HCC risk. For HBV, which accounts for the majority of HCC cases, most infections were acquired via perinatal and early horizontal transmission. Universal vaccination of newborns has led to a decline in HCC incidence compared with the pre-vaccination era. Effective antiviral therapies with nucleos(t)ide analogues or pegylated interferon reduced the incidence of HCC. For HCV, the emergence of effective direct-acting antiviral (DAA) agents has substantially improved cure rates; therefore all patients with HCV should be considered for DAA treatment. The most important obstacle in eliminating HCV is access to therapy. For NAFLD, the global incidence is increasing rapidly, thus its impact on HCC incidence may be explosive. Progression to HCC in NAFLD happens particularly in those with nonalcoholic steatohepatitis (NASH) and exacerbated by metabolic syndrome, or PNPLA3 gene polymorphism. Lifestyle changes are imperative while drug therapy has yet to demonstrate substantive protective effects on HCC prevention. For management of HCC, early diagnosis via imaging surveillance among persons with HCC risk factors remains the most important strategy to identify early-stage disease appropriate for resection or transplantation.

Background There are few published studies to guide the treatment of carcinoma metastatic to the neck from an unknown primary (CUP). In this regard, the objective of the current study was to share the authors' current experience treating patients with CUP using intensity-modulated radiation therapy (IMRT), which principally targeted both sides of the neck, the nasopharynx, and the oropharynx. Methods This was a retrospective study in which an institutional database search was conducted to identify patients with CUP who received IMRT. Data analysis included frequency tabulation, survival analysis, and multivariable analysis. Results Two-hundred sixty patients met inclusion criteria. The most common lymph node category was N2b (54%). IMRT volumes included the entire pharyngolaryngeal mucosa in 78 patients, the nasopharynx and oropharynx in 167 patients, and treatment limited to the involved neck in 11 patients. Eighty-four patients underwent neck dissections. The 5-year overall survival, regional control, and distant metastases-free survival rates were 84%, 91%, and 94%, respectively. Over 40% of patients had gastrostomy tubes during therapy, and 7% patients were diagnosed with chronic radiation-associated dysphagia. Higher lymph node burden was associated with worse disease-related outcomes, and in subgroup analysis, patients with human papillomavirus-associated disease had better outcomes. No therapeutic modality was statistically associated with either disease-related outcomes or toxicity. Conclusions Comprehensive IMRT with treatment to both sides of the neck and to the oropharyngeal and nasopharyngeal mucosa results in high rates of disease control and survival. The investigators were unable to demonstrate that treatment intensification with chemotherapy or surgery added benefit or excessive toxicity. Cancer 2018;124:1415-27. © 2018 American Cancer Society.

To identify a clinically meaningful cut-point for the single item dry mouth question of the MD Anderson Symptom Inventory-Head and Neck module (MDASI-HN).Head and neck cancer survivors who had received radiation therapy (RT) completed the MDASI-HN, the University of Michigan Hospital Xerostomia Questionnaire (XQ), and the health visual analog scale (VAS) of the EuroQol Five Dimension Questionnaire (EQ-5D). The Bayesian information criteria (BIC) were used to test the prediction power of each tool for EQ-5D VAS. The modified Breiman recursive partitioning analysis (RPA) was used to identify a cut point of the MDASI-HN dry mouth score (MDASI-HN-DM) with EQ-5D VAS, using a ROC-based approach; regression analysis was used to confirm the threshold effect size.Two-hundred seven respondents formed the cohort. Median follow-up from the end of RT to questionnaire completion was 88 months. The single item MDASI-HN-DM score showed a linear relationship with the XQ composite score (ρ = 0.80, p 0.001). The MDASI-HN-DM displayed improved model performance for association with EQ-5D VAS as compared to XQ (BIC of 1803.7 vs. 2016.9, respectively). RPA showed that an MDASI-HN-DM score of ≥6 correlated with EQ-5D VAS decline (LogWorth 5.5).The single item MDASI-HN-DM correlated with the multi-item XQ and performed favorably in the prediction of QOL. A MDASI-HN-DM cut point of ≥6 correlated with decline in QOL.

PURPOSE/OBJECTIVE(S) Xerostomia is a common sequela of radiation therapy (RT) and chemoradiotherapy (CRT). Head and neck cancer treatment can contribute to salivary glands injury with diminished salivary production and changes in consistency, volume, and pH of saliva. Previous studies examining xerostomia have investigated RT regimens, dosimetric predictors, and quality of life (QoL) associations but few have identified clinicodemographic risk factors for xerostomia and quantified their associations among oropharyngeal carcinoma (OPC) survivors. The objective of this study was to identify risk factors for xerostomia among long-term OPC survivors. MATERIALS/METHODS This was a cross-sectional study conducted at a comprehensive cancer center. Study participants included disease-free, adult OPC survivors who completed curative definitive radiotherapy treatment between January 2000 and December 2013, and responded to a survey administered from September 2015 to July 2016. This study included 881 OPC survivors with a median survival duration at time of survey of 7 years (range, 1-16 years) of which self-reported xerostomia scores were available for 853 participants. The primary outcome variable was patient-reported xerostomia measured using the MD Anderson Symptom Inventory Head and Neck Cancer Module. Clinicodemographic risk factors for moderate to severe xerostomia were identified using multivariable logistic regression. RESULTS Of 853 OPC survivors who responded to the xerostomia question, 337 (39.5%) reported moderate to severe xerostomia. Multivariable logistic regression identified current smoking at time of survey (OR:2.57, 95% CI: 1.20-5.53, P = 0.016) as a risk factor for moderate to severe xerostomia and concurrent cetuximab chemotherapy (OR:0.63; 95% CI: 0.41-0.97, P = 0.038) as a protective factor. Additionally, female sex (OR:1.81, 95% CI: 1.21-2.71, P = 0.004) and less than high school education (OR:1.68, 95% CI: 1.15-2.45, P = 0.008) were risk factors for moderate to severe xerostomia and bilateral intensity modulated radiotherapy (IMRT) combined with proton therapy (OR:0.34, 95% CI: 1.16-0.73, P = 0.005) and ipsilateral IMRT (OR:0.18, 95% CI: 0.07-0.46, P < 0.001) were protective. CONCLUSION In this large xerostomia study, about 4 out of 10 OPC survivors reported moderate to severe xerostomia over long-term follow-up. Continued smoking after cancer diagnosis, sex, and education were identified as important risk factors of moderate to severe xerostomia and concurrent cetuximab therapy and more modern RT regimens had a protective association. Sustained smoking post-diagnosis is a modifiable risk factor which can be addressed with continued smoking cessation efforts. Lastly, these results can inform future research and targeted patient-centered interventions to monitor and manage RT-associated xerostomia and preserve QoL among OPC patients.

Background The Human papillomavirus (HPV)-related Oropharyngeal and Uncommon Cancers Screening Trial of Men (HOUSTON) was designed to determine the prevalence of IgG antibodies to HPV type 16 E proteins (HPV16EAbs), to screen for persistence of HPV and/or detect HPV-related premalignancies and cancers, and to assess acceptance of screening among middle-aged men. Methods HOUSTON consists of a cross-sectional study and a longitudinal cohort study of men aged 50–64 years. Serologic HPV16EAb status and oral rinse HPV16 status were determined. All HPV16EAb-positive (HPV16EAb+) men and a matched cohort of HPV16EAb-negative (HPV16EAb−) men as well as all oral rinse HPV16-positive (HPV16+) men were included in the longitudinal study (blinded to their results) and underwent oropharyngeal screening every 6 months as well as one-time anal and penile screening. Results Of 553 men enrolled in the cross-sectional study, six (1.1%) were HPV16EAb+ (two were also oral rinse HPV16+), and 41 (7.4%) were HPV16EAb− but oral rinse HPV16+. These 47 men, along with five matched controls, were invited to participate in the longitudinal study, and 42 (81%) agreed and completed baseline in-person screening, with 93% and 90% completeing 6-month and 12-month follow-up visits. One HPV16EAb+ (also oral rinse HPV16+) man, who declined participation in the longitudinal study, presented 4 months after enrollment with an early-stage HPV16-related pharyngeal cancer. Additionally, one HPV16EAb+ (oral rinse HPV16−) man and two oral rinse HPV16+ (HPV16EAb−) men were diagnosed with oncogenic HPV-associated anal dysplasia. Conclusions This biomarker panel deserves further prospective study to explore potential utility for HPV-related cancer screening among men.

Highlights • The prognostic value of pretreatment blood counts is investigated. • This is also done for the nadir neutrophil & lymphocyte levels during radiotherapy. • The impact of treatment modality (IMPT and IMRT) on these nadir levels is examined. • Pretreatment neutrophilia and leukocytosis were associated with worse outcomes. • Treatment modality did not affect blood counts during radiotherapy., Introduction Peripheral blood count components are accessible and evidently predictive in other cancers but have not been explored in oropharyngeal carcinoma. We examine if there is an association between the use of intensity-modulated radiotherapy (IMRT) or intensity-modulated proton therapy (IMPT) and lymphopenia, as well as if there is an association between baseline neutrophilia, baseline leukocytosis and lymphocyte nadir in oropharyngeal cancer. Materials and Methods Analysis started with 150 patients from a previous case to case study design, which retrospectively identified adults with oropharyngeal carcinoma, 100 treated with IMRT in 2010-2012 and 50 treated with IMPT in 2011–2014. Pretreatment leukocyte, neutrophil, lymphocyte, and hemoglobin levels were extracted, as were neutrophil and lymphocyte nadir levels during radiotherapy. We retained 137 patients with recorded pre-treatment leukocyte and neutrophil levels for associated analysis and 114 patients with recorded lymphocyte levels during radiation and associated analysis. Multivariate survival analyses were done with Cox regression. Results The radiotherapy type (IMRT vs. IMPT) was not associated with lymphopenia (grade 3 P > .99; grade 4 P = .55). In univariate analyses, poor overall survival was associated with pretreatment neutrophilia (hazard ratio [HR] 5.58, 95% confidence interval [CI] 1.99–15.7, P = .001), pretreatment leukocytosis (HR 4.85, 95% CI 1.73–13.6, P = .003), grade 4 lymphopenia during radiotherapy (HR 3.28, 95% CI 1.14–9.44, P = .03), and possibly smoking status >10 pack-years (HR 2.88, 95% CI 1.01–8.18, P = .05), but only T status was possibly significant in multivariate analysis (HR 2.64, 95% CI 0.99–7.00, P = .05). Poor progression-free survival was associated with pretreatment leukocytosis and T status in univariate analysis, and pretreatment neutrophilia and advanced age on multivariate analysis. Conclusions Treatment modality did not affect blood counts during radiotherapy. Pretreatment neutrophilia, pretreatment leukocytosis, and grade 4 lymphopenia during radiotherapy were associated with worse outcomes after, but establishing causality will require additional work with increased statistical power.

BACKGROUND Although an association between hepatitis C virus (HCV) infection and oropharyngeal cancers (OPCs) has been reported, to the authors' knowledge the clinical significance of this epidemiological finding remains unknown. Therefore, the authors analyzed the oncologic outcomes of HCV-infected patients with OPCs. METHODS In this retrospective cohort study, all patients with OPCs who were seen at The University of Texas MD Anderson Cancer Center between January 2004 and December 2015 were reviewed. HCV infection was defined as detectable HCV RNA in the serum. Five-year overall survival and progression-free survival rates were compared between patients infected with HCV and those not infected. RESULTS A total of 161 patients were examined. The majority of the patients were white (141 patients; 88%) and male (132 patients; 82%) and had TNM stage III or IV disease (147 patients; 91%). The OPC involved the tonsils (83 patients; 52%), base of the tongue (67patients; 42%), or the soft palate (11 patients; 7%). The median follow-up after an OPC diagnosis was 3 years (range, 1-13 years). HCV-infected patients (25 patients) and HCV-uninfected patients (136 patients) were comparable with regard to smoking and alcohol status. In multivariate analysis, HCV was associated with increased cancer-specific mortality (hazard ratio, 2.15; 95% confidence interval, 1.08-6.85 [P = .02]) and risk of OPC progression (hazard ratio, 5.42; 95% confidence interval, 2.64-11.14 [P = .0008]) independent of age and cirrhosis status. Antivirals were administered after the diagnosis of OPC in 8 of the 25 HCV-infected patients (32%). HCV-infected patients who received antivirals were found to have better 5-year overall survival (70% vs 12%; P = .005) and progression-free survival (72% vs 19%; P = .005) compared with patients who did not. CONCLUSIONS The early detection of HCV is important in patients with OPC because this infection may affect their oncologic outcomes. Cancer 2017. © 2017 American Cancer Society.

To determine dosimetric parameters associated with osteoradionecrosis (ORN) in oropharyngeal cancer (OPC) patients in the IMRT era.Subsequent to institutional review board approval, we identified ORN in OPC patients treated with IMRT from 2002 to 2013. 1:2 case-control matching was implemented. Mandibular dose-volume histograms (DVH) were extracted. Dosimetric parameters were compared using non-parametric stats. Recursive partitioning analysis (RPA) was done to identify DVH correlates of ORN.68 ORN cases and 131 controls were matched. Median follow-up was 41months and median time to development of ORN was 16months. Mandibular mean dose was significantly higher in the ORN cohort (48.1 vs 43.6Gy, p0.0001). However, the maximum dose was not statistically different. DVH bins from V35 to V73 were all significantly higher in the ORN cohort compared with controls (p0.0006). Two DVH parameters were identified in RPA analysis, V43 and V58. The majority (81%) of ORN cases were observed with both V44≥42% and V58≥25%.Our data demonstrate that a wide range of DVH parameters in the intermediate and high beam path were all significantly higher in ORN patients. Mandibular V4442% and V5825% represent reasonable DVH constraints for IMRT plan acceptability, when tumor coverage is not compromised.

BACKGROUND Patients with Fanconi anemia (FA) have an increased risk for head and neck squamous cell carcinoma (HNSCC). The authors sought to determine the prevalence of undiagnosed FA and FA carriers among patients with HNSCC as well as an age cutoff for FA genetic screening. METHODS Germline DNA samples from 417 patients with HNSCC aged

Background High-risk human papillomaviruses (HR-HPV) are the cause of most ano-genital cancers and a fast growing subset of oropharyngeal cancer. As these malignancies occur as a result of an HPV- infection transmitted through intimate contact, many patients with HPV- induced cancer and their partners are concerned about HPV-transmission and the potential partners’ cancer risk. Few studies have addressed this issue and whether the HPV-related cancer risk of partners of patients with HPV-related cancers is comparable to or greater than that of the general population. Methods We performed a systematic review of the published literature addressing this issue. Out of 1055 references screened, 53 articles were found eligible for inclusion. Results Regarding the issue of coincidence of HPV-induced oropharyngeal and/or anogenital cancers in couples, 13 case-reports or case-series were reported and 9 larger studies based on population-registries. Four of these registry studies showed an increased risk of cervical cancer in the partner while four did not. Among the four positive studies, odds ratios for the development of HPV-related cancer among spouses were between 2.6 and 6.7. One study showed an increased risk of tongue or tonsil cancer among husbands of women with cervical dysplasia or cancer. Overall the absolute risk increase in all these studies was small, on the order of 1–3%, although potentially underestimated. Indeed, all these studies have assessed partner’s cancer risk at only one anatomical site whereas HPV- related malignancies can affect different locations. Conclusion This systematic review suggests a small trend of increase risk in HPV-associated cancers among spouses of patients with HPV-related cancer.

Nucleotide excision repair (NER) plays a critical role in the development of smoking-related cancers. We hypothesize that mRNA expression levels of NER genes are associated with risk of the squamous cell carcinoma of head and neck (SCCHN). To test this hypothesis, we conducted a case-control study of 260 SCCHN patients and 246 cancer-free controls by measuring the mRNA expression levels of eight core NER genes in cultured peripheral lymphocytes. Compared with the controls, cases had statistically significantly lower expression levels of DDB1 and ERCC3 (P = 0.015 and 0.041, respectively). Because DDB1 and ERCC3 expression levels were highly correlated, we used DDB1 for further multivariate analyses and modeling. After dividing the subjects by controls' quartiles of expression levels, we found an association between an increased risk of SCCHN and low DDB1 expression levels [adjusted ORs and 95% CIs: 1.92 and 1.11-3.32, 1.48 and 0.85-2.59, 2.00 and 1.15-3.45 for the 2nd-4th quartiles, respectively, compared with the 1st quartile; Ptrend = 0.026]. We also identified a multiplicative interaction between sex and DDB1 expression levels (P = 0.007). Finally, the expanded model with gene expression levels, in addition to demographic and clinical variables, on SCCHN risk was significantly improved, especially among men. In conclusion, reduced DDB1 expression levels were associated with an increased risk of SCCHN. However, these results need to be validated in larger studies.

Background This study investigated the prevalence of and risk factors for oral human papillomavirus (HPV) infection with multiple genotypes in the United States. Methods Data were from the nationally representative 2009-2012 National Health and Nutrition Examination Survey. This analysis comprised 9257 participants for whom data on oral HPV (37 genotypes) and associated risk factors were available. Results The weighted prevalence of multitype (2-6 types) oral HPV infection was 1.5% (2.5% for men, 0.4% for women) in the whole sample and 19.7% (22.0% for men, 12.1% for women) in those who had any type of oral HPV positivity. Most multitype oral HPV cases (83.8%) harbored one or more oncogenic types. In the adjusted multinominal logistic regression model, being male (relative risk ratio [RRR] = 3.69; 95% confidence interval [CI], 1.57-8.65), being a current cigarette smoker (RRR = 2.57; 95% CI, 1.23-5.36), and having a new sex partner in the past year (RRR = 2.10; 95% CI, 1.03-4.28) were associated with an increased risk of multitype oral HPV infection over single-type HPV infection. Conclusions Men, smokers, and those who had new sexual partners were at a significantly higher risk for multitype oral HPV infection.

The purpose is to examine the relationship between mandibular osteoradionecrosis (ORN) and chronic dysphagia in long-term oropharynx cancer (OPC) survivors, and to determine the perceived symptom burden associated with ORN.Medical records of 349 OPC patients treated with bilateral IMRT and systemic therapy were reviewed. ORN was graded using a published 4-point classification schema. Patients were considered to have chronic dysphagia if they had aspiration pneumonia, stricture or aspiration detected by fluoroscopy or endoscopy, and/or feeding tube dependence in long-term follow-up ⩾1year following radiotherapy. MD Anderson Symptom Inventory - Head and Neck Module (MDASI-HN) scores were analyzed in a nested cross-sectional survey sample of 118 patients.34 (9.7%, 95% CI: 6.8-13.3%) patients developed ORN and 45 (12.9%, 95% CI: 9.6-16.9%) patients developed chronic dysphagia. Prevalence of chronic dysphagia was significantly higher in ORN cases (12/34, 35%) compared to those who did not develop ORN (33/315, 11%, p0.001). ORN grade was also significantly associated with prevalence of dysphagia (p0.001); the majority of patients with grade 4 ORN requiring major surgery (6 patients, 75%) were found to have chronic dysphagia. Summary MDASI-HN symptom scores did not significantly differ by ORN grade. Significantly higher symptom burden was reported, however, among ORN cases compared to those without ORN for MDASI-HN swallowing (p=0.033), problems with teeth and/or gums (p=0.016) and change in activity (p=0.015) item scores.ORN is associated with excess burden of chronic dysphagia and higher symptom severity related to swallowing, dentition and activity limitations.

Purpose/Objective Radiation-induced lymphopenia has been associated with poor survival outcomes in certain solid tumors such as esophageal, lung, cervical and pancreatic cancers. We aim to determine the effect of treatment-related lymphopenia during radiotherapy on outcomes of patients with oropharyngeal cancer. Materials/Methods A retrospective analysis of all patients who completed definitive radiotherapy for oropharyngeal cancer at The University of Texas MD Anderson Cancer Center and had blood counts taken during radiotherapy from 2002 to 2013 were included. Patient, tumor and treatment characteristics, clinical outcomes and lymphocyte counts during radiotherapy were recorded. Lymphopenia was graded according to the CTCAE v4.0. Survival rates were estimated using the Kaplan-Meier method and compared with log-rank tests. Results 850 patients were evaluated. The median age was 57 years. The majority of the cohort had p16/HPV-positive disease (71%), 8% had HPV-negative disease and 21% were unknown. The median radiation total dose was 70 Gy. 45% of patients had induction chemotherapy, and 87% had concurrent chemotherapy. 703 (83%) patients developed ≥grade 3 (G3) lymphopenia and 209 (25%) had grade 4 (G4) lymphopenia during radiotherapy. The median follow-up was 59 months; the 5-year overall survival rate was 81%. There were no significant differences in overall survival rates nor in disease control rates, in those who developed G3/G4 lymphopenia compared with those who did not. No significant effect of lymphopenia on survival was observed when analyzed according to p16/HPV status. Conclusion In this large cohort of patients with oropharyngeal cancer, the development of lymphopenia during radiotherapy did not impact outcomes.

Genome-wide association studies (GWASs) have identified at least 10 single-nucleotide polymorphisms (SNPs) associated with papillary thyroid cancer (PTC) risk. Most of these SNPs are common variants with small to moderate effect sizes. Here we assessed the combined genetic effects of these variants on PTC risk by using summarized GWAS results to build polygenic risk score (PRS) models in three PTC study groups from Ohio (1,544 patients and 1,593 controls), Iceland (723 patients and 129,556 controls), and the United Kingdom (534 patients and 407,945 controls). A PRS based on the 10 established PTC SNPs showed a stronger predictive power compared with the clinical factors model, with a minimum increase of area under the receiver-operating curve of 5.4 percentage points ( P ≤ 1.0 × 10 −9 ). Adding an extended PRS based on 592,475 common variants did not significantly improve the prediction power compared with the 10-SNP model, suggesting that most of the remaining undiscovered genetic risk in thyroid cancer is due to rare, moderate- to high-penetrance variants rather than to common low-penetrance variants. Based on the 10-SNP PRS, individuals in the top decile group of PRSs have a close to sevenfold greater risk (95% CI, 5.4–8.8) compared with the bottom decile group. In conclusion, PRSs based on a small number of common germline variants emphasize the importance of heritable low-penetrance markers in PTC.

Publsiher's version (útgefin grein), Thyroid stimulating hormone (TSH) is critical for normal development and metabolism. To better understand the genetic contribution to TSH levels, we conduct a GWAS meta-analysis at 22.4 million genetic markers in up to 119,715 individuals and identify 74 genome-wide significant loci for TSH, of which 28 are previously unreported. Functional experiments show that the thyroglobulin protein-altering variants P118L and G67S impact thyroglobulin secretion. Phenome-wide association analysis in the UK Biobank demonstrates the pleiotropic effects of TSH-associated variants and a polygenic score for higher TSH levels is associated with a reduced risk of thyroid cancer in the UK Biobank and three other independent studies. Two-sample Mendelian randomization using TSH index variants as instrumental variables suggests a protective effect of higher TSH levels (indicating lower thyroid function) on risk of thyroid cancer and goiter. Our findings highlight the pleiotropic effects of TSH-associated variants on thyroid function and growth of malignant and benign thyroid tumors., We acknowledge the University of Michigan Precision Health Initiative and Medical School Central Biorepository for providing biospecimen storage, management, processing, and distribution services, and the Center for Statistical Genetics in the Department of Biostatistics at the School of Public Health for genotype data curation, imputation, and management in support of this research (for MGI cohort). The biochemical work at the University of Michigan was done with funding from NIH R01 DK-40344. This research has been conducted using the UK Biobank Resource under application number 24460. The HUNT Study is a collaboration between the HUNT Research Centre (Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology), Nord-Trøndelag County Council, Central Norway Regional Health Authority, and the Norwegian Institute of Public Health. The genotyping in HUNT was financed by the National Institutes of Health; University of Michigan; the Research Council of Norway; the Liaison Committee for Education, Research and Innovation in Central Norway; and the Joint Research Committee between St Olav’s Hospital and the Faculty of Medicine and Health Sciences, NTNU. We thank Sean Caron for web development for data sharing. Support for this research was provided by NIH grant DK062370 (M.B.). Ohio State Cohort was supported by NIH P50CA168505 SPORE (M.D.R. and A.d.l.C.). Support for the HUNT and MGI analysis was additionally provided by R35HL135824 (C.J.W.) and R01HL109946 (C.J.W.). W.Z. was supported by the National Human Genome Research Institute of the National Institutes of Health under award number T32HG010464. G.D.S., B.B., H.R. and E.B.H. work in the Medical Research Council Integrative Epidemiology Unit at the University of Bristol MC_UU_00011/1.

Background Alcohol is a well-established risk factor for head and neck cancer (HNC). This study aims to explore the effect of alcohol intensity and duration, as joint continuous exposures, on HNC risk. Methods Data from 26 case-control studies in the INHANCE Consortium were used, including never and current drinkers who drunk ≤10 drinks/day for ≤54 years (24234 controls, 4085 oral cavity, 3359 oropharyngeal, 983 hypopharyngeal and 3340 laryngeal cancers). The dose-response relationship between the risk and the joint exposure to drinking intensity and duration was investigated through bivariate regression spline models, adjusting for potential confounders, including tobacco smoking. Results For all subsites, cancer risk steeply increased with increasing drinks/day, with no appreciable threshold effect at lower intensities. For each intensity level, the risk of oral cavity, hypopharyngeal and laryngeal cancers did not vary according to years of drinking, suggesting no effect of duration. For oropharyngeal cancer, the risk increased with durations up to 28 years, flattening thereafter. The risk peaked at the higher levels of intensity and duration for all subsites (odds ratio = 7.95 for oral cavity, 12.86 for oropharynx, 24.96 for hypopharynx and 6.60 for larynx). Conclusions Present results further encourage the reduction of alcohol intensity to mitigate HNC risk.