Can predictive factors determine the time to treatment initiation for oral and oropharyngeal cancer? A classification and regression tree analysis.

This ecological study aimed to identify the factors with the greatest power to discriminate the proportion of oral and oropharyngeal cancer (OOC) records with time to treatment initiation (TTI) within 30 days of diagnosis in Brazilian municipalities. A descriptive analysis was performed on the variables grouped into five dimensions related to patient characteristics, access to health services, support for cancer diagnosis, human resources, and socioeconomic characteristics of 3,218 Brazilian municipalities that registered at least one case of OOC in 2019. The Classification and Regression Trees (CART) technique was adopted to identify the explanatory variables with greater discriminatory power for the TTI response variable. There was a higher median percentage of records in the age group of 60 years or older. The median percentage of records with stage III and IV of the disease was 46.97%, and of records with chemotherapy, radiation, or both as the first treatment was 50%. The median percentage of people with private dental and health insurance was low. Up to 75% had no cancer diagnostic support services, and up to 50% of the municipalities had no specialist dentists. Most municipalities (49.4%) started treatment after more than 30 days. In the CART analysis, treatment with chemotherapy, radiotherapy, or both explained the highest TTI in all municipalities, and it was the most relevant for predicting TTI. The final model also included anatomical sites in the oral cavity and oropharynx and the number of computed tomography services per 100,000. There is a need to expand the availability of oncology services and human resources specialized in diagnosing and treating OOC in Brazilian municipalities for a timely TTI of OOC.

Therapeutic Advances and Challenges for the Management of HPV-Associated Oropharyngeal Cancer.

The use of conventional chemotherapy in conjunction with targeted and immunotherapy drugs has emerged as an option to limit the severity of side effects in patients diagnosed with head and neck cancer (HNC), particularly oropharyngeal cancer (OPC). OPC prevalence has increased exponentially in the past 30 years due to the prevalence of human papillomavirus (HPV) infection. This study reports a comprehensive review of clinical trials registered in public databases and reported in the literature (PubMed/Medline, Scopus, and ISI web of science databases). Of the 55 clinical trials identified, the majority (83.3%) were conducted after 2015, of which 77.7% were performed in the United States alone. Eight drugs have been approved by the FDA for HNC, including both generic and commercial forms: bleomycin sulfate, cetuximab (Erbitux), docetaxel (Taxotere), hydroxyurea (Hydrea), pembrolizumab (Keytruda), loqtorzi (Toripalimab-tpzi), methotrexate sodium (Trexall), and nivolumab (Opdivo). The most common drugs to treat HPV-associated OPC under these clinical trials and implemented as well for HPV-negative HNC include cisplatin, nivolumab, cetuximab, paclitaxel, pembrolizumab, 5-fluorouracil, and docetaxel. Few studies have highlighted the necessity for new drugs specifically tailored to patients with HPV-associated OPC, where molecular mechanisms and clinical prognosis are distinct from HPV-negative tumors. In this context, we identified most mutated genes found in HPV-associated OPC that can represent potential targets for drug development. These include TP53, PIK3CA, PTEN, NOTCH1, RB1, FAT1, FBXW7, HRAS, KRAS, and CDKN2A.

Clinical and prognostic differences in oropharyngeal squamous cell carcinoma in USA and Denmark, two HPV high-prevalence areas.

BACKGROUND: Uncertainty persists regarding clinical and treatment variations crucial to consider when comparing high human papillomavirus (HPV)-prevalence oropharyngeal squamous cell carcinoma (OPSCC) cohorts for accurate patient stratification and replicability of clinical trials across different geographical areas. METHODS: OPSCC patients were included from The University of Texas MD Anderson Cancer Center (UTMDACC), USA and from The University Hospital of Copenhagen, Denmark from 2015-2020, (n = 2484). Outcomes were 3-year overall survival (OS) and recurrence-free interval (RFI). Subgroup analyses were made for low-risk OPSCC patients (T1-2N0M0) and high-risk patients (UICC8 III-IV). RESULTS: There were significantly more HPV-positive (88.2 % vs. 63.1 %), males (89.4 % vs. 74.1 %), never-smokers (52.1 % vs. 23.7 %), lower UICC8-stage (I/II: 79.3 % vs. 68 %), and fewer patients treated with radiotherapy (RT) alone (14.8 % vs. 30.3 %) in the UTMDACC cohort. No difference in the adjusted OS was observed (hazard ratio [HR] 1.21, p = 0.23), but a significantly increased RFI HR was observed for the Copenhagen cohort (HR: 1.74, p = 0.003). Subgroup analyses of low- and high-risk patients revealed significant clinical and treatment differences. No difference in prognosis was observed for low-risk patients, but the prognosis for high-risk patients in the Copenhagen cohort was worse (OS HR 2.20, p = 0.004, RFI HR 2.80, p = 0.002). CONCLUSIONS: We identified significant differences in clinical characteristics, treatment modalities, and prognosis between a Northern European and Northern American OPSCC population. These differences are important to consider when comparing outcomes and for patient stratification in clinical trials, as reproducibility might be challenging.

Mapping the research landscape of HPV-positive oropharyngeal cancer: a bibliometric analysis.

OBJECTIVE: The aim of the study is to evaluate the scientific interest, the collaboration patterns and the emerging trends regarding HPV+ OPSCC diagnosis and treatment. MATERIALS AND METHODS: A cross-sectional bibliometric analysis of articles reporting on HPV+ OPSCC within Scopus database was performed and all documents published up to December 31th, 2022 were eligible for analysis. Outcomes included the exploration of key characteristics (number of manuscripts published per year, growth rate, top productive countries, most highly cited papers, and the most well-represented journals), collaboration parameters (international collaboration ratio and networks, co-occurrence networks), keywords analysis (trend topics, factorial analysis). RESULTS: A total of 5200 documents were found, published from March, 1987 to December, 2022. The number of publications increased annually with an average growth rate of 19.94%, reaching a peak of 680 documents published in 2021. The 10 most cited documents (range 1105-4645) were published from 2000 to 2012. The keywords factorial analysis revealed two main clusters: one on epidemiology, diagnosis, prevention and association with other HPV tumors; the other one about the therapeutic options. According to the frequency of keywords, new items are emerging in the last three years regarding the application of Artifical Intelligence (machine learning and radiomics) and the diagnostic biomarkers (circulating tumor DNA). CONCLUSIONS: This bibliometric analysis highlights the importance of research efforts in prevention, diagnostics, and treatment strategies for this disease. Given the urgency of optimizing treatment and improving clinical outcomes, further clinical trials are needed to bridge unaddressed gaps in the management of HPV+ OPSCC patients.

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

PURPOSE: The incidence of oral cancers, particularly HPV-related oropharyngeal cancer, is steadily increasing worldwide, presenting a significant healthcare challenge. This study investigates trends and predictors of unplanned hospitalizations for oral cavity cancer (OCC) and oropharyngeal cancer (OPC) patients in the province of Alberta, Canada. METHODS: This retrospective, population-based, cohort study used administrative data collected from all hospitals in the province. Using the Alberta Cancer Registry (ACR), a cohort of adult patients diagnosed with a single primary OCC or OPC between January 2010 and December 2017 was identified. Linking this cohort with the Discharge Abstract Database (DAD), trends in hospitalizations, primary diagnoses, and predictors of unplanned hospitalization (UH) and 30-day unplanned readmission were analyzed. RESULTS: Of 1,721 patients included, 1,244 experienced 2,228 hospitalizations, with 48 % being categorized as UH. The UHs were significantly associated with a higher mortality rate, 18.5 % as compared to 4.6 % for planned, and influenced by sex, age groups, comorbidities, cancer types, stages, and treatment modalities. The rate of UH per patient decreased from 0.69 to 0.54 visits during the study period (P = 0.02). Common diagnoses for UH were palliative care and post-surgical convalescence, while surgery-related complications such as infection and hemorrhage were frequent in 30-day unplanned readmissions. Predictors of UH included cancer stage, material deprivation, and treatment, while cancer type and comorbidity predicted readmissions. CONCLUSION: The rate of UHs showed a noteworthy decline in this study, which could be a result of enhanced care coordination. Furthermore, identified primary diagnosis and predictors associated with UHs and readmissions, provide valuable insights for enhancing the quality of care for cancer patients.

Rethinking treatment paradigms: Neoadjuvant therapy and de-escalation strategies in HPV-positive head and neck cancer.

Head and neck cancer (HNC) is the 6th most common cancer across the world, with a particular increase in HNC associated with human papilloma virus (HPV) among younger populations. Historically, the standard treatment for this disease consisted of combined surgery and radiotherapy or curative platinum-based concurrent chemoradiotherapy, with associated long term and late toxicities. However, HPV-positive HNC is recognized as a unique cancer subtype, typically with improved clinical outcomes. As such, treatment de-escalation strategies have been widely researched to mitigate the adverse effects associated with the current standard of care without compromising efficacy. These strategies include treatment de-escalation, such as novel surgical techniques, alternative radiation technologies, radiation dose and volume reduction, as well as neoadjuvant chemotherapies, immunotherapies, and combined therapies. Although these therapies show great promise, many of them are still under investigation due to hesitation surrounding their widespread implementation. The objective of this review is to summarize the most recent progress in de-escalation strategies and neoadjuvant therapies designed for HPV-positive HNC. While specific treatments may require additional research before being widely adopted, encouraging results from recent studies have highlighted the advantages of neoadjuvant chemotherapy and immunotherapy, as well as radiation and surgical de-escalation approaches in managing HPV-positive HNC.

Surrogate endpoints in clinical trials of p16-positive squamous cell carcinoma of the oropharynx: an individual patient data meta-analysis.

BACKGROUND: The increased incidence of human papillomavirus (HPV)-related cancers has motivated efforts to optimise treatment for these patients with excellent prognosis. Validation of surrogates for overall survival could expedite the investigation of new therapies. We sought to evaluate candidate intermediate clinical endpoints in trials assessing definitive treatment of p16-positive oropharyngeal cancer with chemotherapy or radiotherapy. METHODS: We did a retrospective review of five multicentre, randomised trials (NRG/RTOG 9003, 0129, 0234, 0522, and 1016) that tested radiotherapy with or without chemotherapy in patients (aged ≥18 years) with p16-positive localised head or neck squamous-cell carcinomas. Eight intermediate clinical endpoints were considered as potential surrogates for overall survival: freedom from local progression, freedom from regional progression, freedom from distant metastasis, freedom from locoregional progression, freedom from any progression, locoregional progression-free survival, progression-free survival, and distant metastasis-free survival. We used a two-stage meta-analytical framework, which requires high correlation between the intermediate clinical endpoint and overall survival at the patient level (condition 1), and high correlation between the treatment effect on the intermediate clinical endpoint and the treatment effect on overall survival (condition 2). For both, an r2 greater than 0·7 was used as criteria for clinically relevant surrogacy. FINDINGS: We analysed 1373 patients with oropharyngeal cancer from May 9, 2020, to Nov 22, 2023. 1231 (90%) of patients were men, 142 (10%) were women, and 1207 (88%) were White, with a median age of 57 years (IQR 51-62). Median follow-up was 4·2 years (3·1-5·1). For the first condition, correlating the intermediate clinical endpoints with overall survival at the individual and trial level, the three composite endpoints of locoregional progression-free survival (Kendall's τ 0·91 and r2 0·72), distant metastasis-free survival (Kendall's τ 0·93 and r2 0·83), and progression-free survival (Kendall's τ 0·88 and r2 0·70) were highly correlated with overall survival at the patient level and at the trial-group level. For the second condition, correlating treatment effects of the intermediate clinical endpoints and overall survival, the composite endpoints of locoregional progression-free survival (r2 0·88), distant metastasis-free survival (r2 0·96), and progression-free survival (r2 0·92) remained strong surrogates. Treatment effects on the remaining intermediate clinical endpoints were less strongly correlated with overall survival. INTERPRETATION: We identified locoregional progression-free survival, distant metastasis-free survival, and progression-free survival as surrogates for overall survival in p16-positive oropharyngeal cancers treated with chemotherapy or radiotherapy, which could serve as clinical trial endpoints. FUNDING: NRG Oncology Operations, NRG Oncology SDMC, the National Cancer Institute, Eli Lilly, Aventis, and the University of Michigan.

Acute and definitive management of oropharyngeal hemorrhage in patients with squamous cell carcinoma of the oropharynx.

BACKGROUND: Massive oropharyngeal bleeding post-chemoradiotherapy is a life-threatening condition that requires emergent management. METHODS: This retrospective case series included 11 patients with oropharyngeal squamous cell carcinoma who suffered from massive bleeding during or following treatment with definitive chemoradiotherapy. Details of acute and definitive management of oropharyngeal bleeding are reported. RESULTS: Nine of 11 hemorrhagic events occurred a mean (SD) of 88.6 days (53.6) after radiotherapy. Airway intubation and embolization were performed in 10 of 11 patients, followed by surgery in 7 of 11 patients. The most commonly embolized vessels were the external carotid and lingual arteries. At the time of discharge, 3 of 11 patients had a tracheostomy, and 7 of 11 continued to use a gastrostomy tube. Four patients died. CONCLUSIONS: Hemorrhagic complications in oropharyngeal cancer treatment require emergent responses. Developing a workflow for coordination between multidisciplinary teams can maximize probability of survival and decrease morbidity.

Hypoxia-Directed Treatment of Human Papillomavirus-Related Oropharyngeal Carcinoma.

PURPOSE: Standard curative-intent chemoradiotherapy for human papillomavirus (HPV)-related oropharyngeal carcinoma results in significant toxicity. Since hypoxic tumors are radioresistant, we posited that the aerobic state of a tumor could identify patients eligible for de-escalation of chemoradiotherapy while maintaining treatment efficacy. METHODS: We enrolled patients with HPV-related oropharyngeal carcinoma to receive de-escalated definitive chemoradiotherapy in a phase II study (ClinicalTrials.gov identifier: NCT03323463). Patients first underwent surgical removal of disease at their primary site, but not of gross disease in the neck. A baseline 18F-fluoromisonidazole positron emission tomography scan was used to measure tumor hypoxia and was repeated 1-2 weeks intratreatment. Patients with nonhypoxic tumors received 30 Gy (3 weeks) with chemotherapy, whereas those with hypoxic tumors received standard chemoradiotherapy to 70 Gy (7 weeks). The primary objective was achieving a 2-year locoregional control (LRC) of 95% with a 7% noninferiority margin. RESULTS: One hundred fifty-eight patients with T0-2/N1-N2c were enrolled, of which 152 patients were eligible for analyses. Of these, 128 patients met criteria for 30 Gy and 24 patients received 70 Gy. The 2-year LRC was 94.7% (95% CI, 89.8 to 97.7), meeting our primary objective. With a median follow-up time of 38.3 (range, 22.1-58.4) months, the 2-year progression-free survival (PFS) and overall survival (OS) rates were 94% and 100%, respectively, for the 30-Gy cohort. The 70-Gy cohort had similar 2-year PFS and OS rates at 96% and 96%, respectively. Acute grade 3-4 adverse events were more common in 70 Gy versus 30 Gy (58.3% v 32%; P = .02). Late grade 3-4 adverse events only occurred in the 70-Gy cohort, in which 4.5% complained of late dysphagia. CONCLUSION: Tumor hypoxia is a promising approach to direct dosing of curative-intent chemoradiotherapy for HPV-related carcinomas with preserved efficacy and substantially reduced toxicity that requires further investigation.

CompARE: study protocol for a phase III randomised controlled platform trial comparing alternative regimens for escalating treatment of intermediate and high-risk oropharyngeal cancer.

BACKGROUND: Patients with intermediate and high-risk oropharyngeal cancer (OPC) have poorer response to standard treatment and poorer overall survival compared to low-risk OPC. CompARE is designed to test alternative approaches to intensified treatment for these patients to improve survival. METHODS: CompARE is a pragmatic phase III, open-label, multicenter randomised controlled trial with an adaptive multi-arm, multi-stage design and an integrated QuinteT Recruitment Intervention. Eligible OPC patients include those with human papillomavirus (HPV) negative, T1-T4, N1-N3 or T3-4, N0, or HPV positive N3, T4, or current smokers (or ≥ 10 pack years previous smoking history) with T1-T4, N2b-N3. CompARE was originally designed with four arms (one control [arm 1] and three experimental: arm 2-induction chemotherapy followed by arm 1; arm 3-dose-escalated radiotherapy plus concomitant cisplatin; and arm 4-resection of primary followed by arm 1). The three original experimental arms have been closed to recruitment and a further experimental arm opened (arm 5-induction durvalumab followed by arm 1 and then adjuvant durvalumab). Currently recruiting are arm 1 (control): standard treatment of 3-weekly cisplatin 100 mg/m2 or weekly 40 mg/m2 with intensity-modulated radiotherapy using 70 Gy in 35 fractions ± neck dissection determined by clinical and radiological assessment 3 months post-treatment, and arm 5 (intervention): one cycle of induction durvalumab 1500 mg followed by standard treatment then durvalumab 1500 mg every 4 weeks for a total of 6 months. The definitive and interim primary outcome measures are overall survival time and event-free survival (EFS) time, respectively. Secondary outcome measures include quality of life, toxicity, swallowing outcomes, feeding tube incidence, surgical complication rates, and cost-effectiveness. The design anticipates that after approximately 7 years, 84 required events will have occurred to enable analysis of the definitive primary outcome measure for this comparison. Planned interim futility analyses using EFS will also be performed. DISCUSSION: CompARE is designed to be efficient and cost-effective in response to new data, emerging new treatments or difficulties, with the aim of bringing new treatment options for these patients. TRIAL REGISTRATION: ISRCTN ISRCTN41478539 . Registered on 29 April 2015.

Unveiling Liquid Gold: Lymph as an HPV Marker in OPSCC to Guide Treatment Decisions.

Distinguishing low- versus high-risk HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) is pivotal for tailoring treatment. Liquid biopsy, measuring cell-free HPV-DNA in serum and saliva, assesses treatment response and early-recurrence risk. Postoperative lymphatic fluid may better guide future adjuvant therapy decisions due to its proximity to primary lesions and lymph nodes. See related article by Earland et al., p. 1409.

Developing and Validating a Multivariable Prognostic-Predictive Classifier for Treatment Escalation of Oropharyngeal Squamous Cell Carcinoma: The PREDICTR-OPC Study.

PURPOSE: While there are several prognostic classifiers, to date, there are no validated predictive models that inform treatment selection for oropharyngeal squamous cell carcinoma (OPSCC).Our aim was to develop clinical and/or biomarker predictive models for patient outcome and treatment escalation for OPSCC. EXPERIMENTAL DESIGN: We retrospectively collated clinical data and samples from a consecutive cohort of OPSCC cases treated with curative intent at ten secondary care centers in United Kingdom and Poland between 1999 and 2012. We constructed tissue microarrays, which were stained and scored for 10 biomarkers. We then undertook multivariable regression of eight clinical parameters and 10 biomarkers on a development cohort of 600 patients. Models were validated on an independent, retrospectively collected, 385-patient cohort. RESULTS: A total of 985 subjects (median follow-up 5.03 years, range: 4.73-5.21 years) were included. The final biomarker classifier, comprising p16 and survivin immunohistochemistry, high-risk human papillomavirus (HPV) DNA in situ hybridization, and tumor-infiltrating lymphocytes, predicted benefit from combined surgery + adjuvant chemo/radiotherapy over primary chemoradiotherapy in the high-risk group [3-year overall survival (OS) 63.1% vs. 41.1%, respectively, HR = 0.32; 95% confidence interval (CI), 0.16-0.65; P = 0.002], but not in the low-risk group (HR = 0.4; 95% CI, 0.14-1.24; P = 0.114). On further adjustment by propensity scores, the adjusted HR in the high-risk group was 0.34, 95% CI = 0.17-0.67, P = 0.002, and in the low-risk group HR was 0.5, 95% CI = 0.1-2.38, P = 0.384. The concordance index was 0.73. CONCLUSIONS: We have developed a prognostic classifier, which also appears to demonstrate moderate predictive ability. External validation in a prospective setting is now underway to confirm this and prepare for clinical adoption.

Association of follow-up imaging frequency with temporal incidence and patterns of distant failure following (chemo) radiotherapy for HPV related oropharyngeal cancer.

OBJECTIVES: Emerging data supports radical intent therapy for oligometastatic (OM) relapsed human papilloma virus (HPV+) related oropharyngeal cancer (OPC). We assess the association of follow-up imaging frequency amongst HPV + OPC, with temporal and spatial patterns of distant relapse, to inform rationalisation of routine post-treatment imaging. MATERIALS AND METHODS: A retrospective single centre cohort study was carried out of consecutive HPV + OPC patients treated with radical intent (chemo)radiotherapy ((CT)RT) between 2011 and 2019. OM state was defined as ≤ 5 metastasis, none larger than 3 cm (OMs) or, if interval from last negative surveillance imaging > 6-months, then ≤ 10 metastasis, none larger than 5 cm, (OMp). Patients not meeting OMs / OMp criteria were deemed to have incurable diffuse metastatic disease (DMdiffuse). RESULTS: 793 HPV-OPC patients were identified with median follow-up 3.15years (range 0.2-8.9). 52 (6.6 %) patients had radiologically identified DM at first failure and were considered for analysis. The median time to recurrence was 15.1 months (range: 2.6-63 months). 87 % of distant metastasis (DM) occurred in the first two years after treatment. Twenty-seven (52 %) patients had OM (OMs or OMp) at time of failure, with 31 % having OMs. The median time from completion of treatment to diagnosis of DMdiffuse vs OM was 22.2 months (range: 2.6-63.1 months) vs 11.6 months (range: 3.5-32.5 months). The probability of being diagnosed with OM vs DMdiffuse increased with reducing interval from last negative surveillance scan to imaging identifying DM (≤6 months 88.9 %, 7-12 months 71.4 %, 13-24 months 35 %, > 24 months 22.2 %). CONCLUSION: We demonstrate that a reduced interval between last negative imaging and subsequent radiological diagnosis of DM is associated with increased likelihood of identification of OM disease. Consideration of increased frequency of surveillance imaging during the first two years of follow up is supported, particularly for patients at high risk of distant failure.

Longitudinal Pattern of Lymphedema and Fibrosis in Patients With Oral Cavity or Oropharyngeal Cancer: A Prospective Study.

PURPOSE: The study aimed to describe the prevalence, severity, and trajectory of internal lymphedema, external lymphedema, and fibrosis in patients with oral cavity or oropharyngeal (OCOP) cancer. METHODS AND MATERIALS: One hundred twenty patients with newly diagnosed OCOP cancer were enrolled in a prospective longitudinal study. Recruitment was conducted at a comprehensive medical center. Participants were assessed pretreatment; at end of treatment; and at 3, 6, 9, and 12 months post-cancer treatment. Validated clinician-reported measures and computed tomography were used to assess the study outcomes. RESULTS: Seventy-six patients who completed the 9- or 12-month assessments were included in this report. Examination of the external lymphedema and fibrosis trajectories revealed that the total severity score peaked between the end of treatment and 3 months posttreatment and then decreased gradually over time but did not return to baseline by 12 months posttreatment (P < .001). The longitudinal patterns of severity scores for patients treated with surgery only or with multimodality therapy were similar. Examination of the internal swelling trajectories revealed that all patients experienced a significant increase in sites with swelling immediately posttreatment. For patients treated with surgery only, swelling was minimal and returned to baseline by 9 to 12 months posttreatment. Patients receiving multimodal treatment experienced a gradual decrease in number of sites with swelling during the 12-month posttreatment period that remained significantly above baseline (P < .05). Computed tomography revealed different patterns of changes in prevertebral soft tissue and epiglottic thickness in the surgery-only and multimodality treatment groups during the 12-month posttreatment period. There were minimal changes in thickness in both regions in the surgery-only group. Patients with multimodal treatment had significant increases in thickness in both regions 3 months posttreatment that remained thicker at 12 months than at baseline (P < .001). CONCLUSIONS: Lymphedema and fibrosis are the common complications of OCOP cancer therapy. Routine assessment, monitoring, and timely treatment of lymphedema and fibrosis are critical.

A Longitudinal Study Evaluating Sexual Health Outcomes and Prioritization in Patients Undergoing Chemoradiation for Human Papillomavirus-Associated Oropharyngeal Cancer.

PURPOSE: The primary objectives were to describe the longitudinal course of sexual health in people undergoing curative (chemo)radiation therapy ([C)RT) for human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPVOPSCC) and identify factors associated with higher sexual satisfaction 12 months after (C)RT. METHODS AND MATERIALS: Eligible participants from 3 sites were recruited to a prospective observational study between October 2020 and November 2021. Measures of sexual health (22-item European Organization for Research and Treatment of Cancer Sexual Health Questionnaire), treatment outcome priorities (Chicago Priorities Scale), quality of life (30-item European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire), symptom burden (MD Anderson Symptom Inventory-Head and Neck), emotional distress (Patient-Reported Outcomes Measurement Information System - Anxiety and Depression), and facial appearance and appearance distress (FACE-Q) were administered before, at the end, and 3 and 12 months after (C)RT. RESULTS: Of 128 eligible participants, 100 were recruited; sexual health measure data were available for 89 of 98 patients alive at 12 months. Mean sexual satisfaction scores were 51.8 (SD = 26.6) before (C)RT. Mixed model results indicated a clinically significant reduction in sexual satisfaction by the end of (-25.4; 95% CI, -30.7 to -20.2) and 3 months after CRT (-12.2; -17.3 to -7.0) but not 12 months after CRT (-3.8; 95% CI, -9.0 to 1.4). Of 13 treatment outcome priorities, "keeping sexual function" had a median rank of 10 and 9 before and 12 months after (C)RT, respectively; 24% and 26% identified it as a top priority at these times. Cohabiting, having a sexual partner, being sexually active, higher global health status, lower sexual health issues, lower depression, and considering sexual function a top priority were associated with higher sexual satisfaction scores 12 months after (C)RT. CONCLUSIONS: Although affected acutely by (C)RT, average sexual satisfaction returned to near pretreatment levels after 12 months. Sexual function is considered a top survivorship priority by approximately one-quarter of patients with HPVOPSCC.

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.