Prevalence of human papillomavirus in head and neck cancers at tertiary care centers in the United States over time.

BACKGROUND: Human papillomavirus (HPV) is responsible for a growing proportion of oropharyngeal squamous cell carcinomas (OPSCCs) among men and White individuals. Whether similar trends apply to women, non-Whites, and non-oropharyngeal squamous cell carcinomas (non-OPSCCs) is unknown. METHODS: This is a cross-sectional analysis combining 2 multi-institutional case series of incident head and neck squamous cell carcinoma (HNSCC) cases. Incident HNSCCs from 1995 to 2012 were enrolled retrospectively using banked tumor samples and medical record abstraction. Incident HNSCCs from 2013 to 2019 were enrolled prospectively. The prevalence of tumor HPV biomarkers was tested over 3 time periods (1995-2003, 2004-2012, and 2013-2019). Centralized testing was done for p16 immunohistochemistry (p16) and oncogenic HPV in situ hybridization (ISH). RESULTS: A total of 1209 incident cases of HNSCC were included. Prevalence of p16- and ISH-positive tumors increased significantly for oropharynx cancers over time. The majority were positive after 2013 for White patients (p16, 92%; P < .001; ISH 94%; P < .001), Black patients (p16, 72%; P = .021; ISH 67%; P = .011), and Hispanic patients (p16, 100%; P = .04; ISH 100%; P = .013). For women with OPSCC, the prevalence of p16- and ISH-positive tumors increased significantly to 82% (P < .001) and 78% (P = .004), respectively. For non-OPSCCs, there was increased p16 and ISH positivity overall with 24% p16 and 16% ISH positivity in the most recent time period (P < .001 for both). CONCLUSIONS: The majority of OPSCCs in US tertiary care centers are now p16 and ISH positive for all sex and race groups. In some populations in the United States, 91% of OPSCCs are now caused by HPV. Few non-OPSCCs are p16 and ISH positive.

Timing, number, and type of sexual partners associated with risk of oropharyngeal cancer.

BACKGROUND: Case-control studies from the early 2000s demonstrated that human papillomavirus-related oropharyngeal cancer (HPV-OPC) is a distinct entity associated with number of oral sex partners. Using contemporary data, we investigated novel risk factors (sexual debut behaviors, exposure intensity, and relationship dynamics) and serological markers on odds of HPV-OPC. METHODS: HPV-OPC patients and frequency-matched controls were enrolled in a multicenter study from 2013 to 2018. Participants completed a behavioral survey. Characteristics were compared using a chi-square test for categorical variables and a t test for continuous variables. Adjusted odds ratios (aOR) were calculated using logistic regression. RESULTS: A total of 163 HPV-OPC patients and 345 controls were included. Lifetime number of oral sex partners was associated with significantly increased odds of HPV-OPC (>10 partners: odds ratio [OR], 4.3 [95% CI, 2.8-6.7]). After adjustment for number of oral sex partners and smoking, younger age at first oral sex (<18 vs >20 years: aOR, 1.8 [95% CI, 1.1-3.2]) and oral sex intensity (>5 sex-years: aOR, 2.8 [95% CI, 1.1-7.5]) remained associated with significantly increased odds of HPV-OPC. Type of sexual partner such as older partners when a case was younger (OR, 1.7 [95% CI, 1.1-2.6]) or having a partner who had extramarital sex (OR, 1.6 [95% CI, 1.1-2.4]) was associated with HPV-OPC. Seropositivity for antibodies to HPV16 E6 (OR, 286 [95% CI, 122-670]) and any HPV16 E protein (E1, E2, E6, E7; OR, 163 [95% CI, 70-378]) was associated with increased odds of HPV-OPC. CONCLUSION: Number of oral sex partners remains a strong risk factor for HPV-OPC; however, timing and intensity of oral sex are novel independent risk factors. These behaviors suggest additional nuances of how and why some individuals develop HPV-OPC.

RTOG-0129 risk groups are reproducible in a prospective multicenter heterogeneously treated cohort.

BACKGROUND: Recursive partitioning analysis (RPA) from the Radiation Therapy Oncology Group (RTOG)-0129 has identified a low-risk group of patients with oropharynx cancer (OPC) who might benefit from therapeutic de-intensification. These risk groups have not yet been reproduced in an independent cohort treated heterogeneously. Therefore, the objective of this analysis was to validate the RPA risk groups and examine the prognostic impact of novel factors. METHODS: Patients with OPC were enrolled in a prospective study at 3 academic medical centers from 2013 to 2018. Medical record abstraction was used to ascertain clinical variables including staging and survival according to the 7th edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual. Human papillomavirus-positive tumor status was determined by p16 immunohistochemistry and/or HPV RNA in situ hybridization. Kaplan-Meier and log-rank methods were used to compare survival. Cox proportional hazards were used to generate univariate and multivariable hazard ratios (HRs). RESULTS: Median follow-up time was 3.2 years. The low-, intermediate-, and high-risk groups had significant differences in 2-year overall survival (OS, 99.1%; 95% CI, 94.4%-99.9% vs OS, 93.0%; 95% CI, 74.7%-98.2% vs OS, 80.0%; 95% CI, 40.9%-94.6%; Poverall = .0001) and 2-year progression-free survival (PFS, 97.5%; 95% CI, 92.4%-99.2% vs PFS, 89.3%; 95% CI, 70.3%-96.4% vs PFS, 80.0%; 95% CI, 40.9%-94.6%; Poverall < .002). After adjustment for age, sex, and level of educational attainment, OS and PFS were significantly lower for the intermediate- (OS adjusted hazard ratio [aHR], 5.0; 95% CI, 1.0-23.0; PFS aHR, 3.4; 95% CI, 1.0-11.5), and high- (OS aHR, 7.3; 95% CI, 1.4-39; PFS aHR, 5.0; 95% CI, 1.2-21.6) risk groups compared with the low-risk group. Lower education was also independently significantly associated with worse OS (aHR, 8.9; 95% CI, 1.8-44.3) and PFS (aHR, 3.1; 95% CI, 1.0-9.6). CONCLUSIONS: In patients with OPC, the RTOG-0129 RPA model is associated with OS and PFS in a heterogeneously treated cohort.

Priorities, concerns, and regret among patients with head and neck cancer.

BACKGROUND: In the era of deintensification, little data are available regarding patients' treatment preferences. The current study evaluated treatment-related priorities, concerns, and regret among patients with head and neck squamous cell cancer (HNSCC). METHODS: A total of 150 patients with HNSCC ranked the importance of 10 nononcologic treatment goals relative to the oncologic goals of cure and survival. The level of concern regarding 11 issues and decision regret was recorded. Median rank was reported overall, and factors associated with odds of rank as a top 3 priority were modeled using logistic regression. RESULTS: Among the treatment effects analyzed, the odds of being a top 3 priority was especially high for cure (odds, 9.17; 95% confidence interval [95% CI], 5.05-16.63), followed by survival and swallow (odds, 1.26 [95% CI, 0.88-1.80] and odds, 0.85 [95% CI, 0.59-1.21], respectively). Prioritization of cure, survival, and swallow was similar based on human papillomavirus (HPV) tumor status. By increasing decade of age, older participants were found to be significantly less likely than younger individuals to prioritize survival (odds ratio, 0.72; 95% CI, 0.52-1.00). Concerns regarding mortality (P = .04) and transmission of HPV to the patient's spouse (P = .03) were more frequent among participants with HPV-associated HNSCC. Regret increased with additional treatment modalities (P = .02). CONCLUSIONS: Patients with HNSCC overwhelming prioritize cure, followed by survival and swallow. The decreased prioritization of survival by older age supports further examination of treatment preference by age. The precedence of oncologic over nononcologic priorities among patients regardless of HPV tumor status supports the conservative adoption of deintensification regimens until the interplay between competing oncologic and nononcologic treatment goals is better understood.

Increasing prevalence of human papillomavirus-positive oropharyngeal cancers among older adults.

BACKGROUND: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing among older adults. It is unknown whether these trends can be explained by human papillomavirus (HPV) and whether HPV-related tumors remain associated with an improved prognosis among older patients. METHODS: In a retrospective study of OPSCCs diagnosed from 1995 to 2013 at 2 National Comprehensive Cancer Network-designated cancer centers, p16 immunohistochemistry and in situ hybridization (ISH) for HPV-16, high-risk DNA, and/or E6/E7 RNA were performed. The median age at diagnosis was compared by p16 and ISH tumor status. Trends in age were analyzed with nonparametric trends. Survival was analyzed with the Kaplan-Meier method and Cox proportional hazards models. RESULTS: Among 239 patients, 144 (60%) were p16-positive. During 1998-2013, the median age increased among p16-positive patients (Ptrend = .01) but not among p16-negative patients (Ptrend = .71). The median age of p16-positive patients increased from 53 years (interquartile range [IQR] in 1995-2000, 45-65 years) to 58 years (IQR for 2001-2013, 53-64 years). Among patients ≥ 65 years old, the proportion of OPSCCs that were p16-positive increased from 41% during 1995-2000 to 75% during 2007-2013 (Ptrend = .04). Among all age groups, including older patients, a p16-positive tumor status conferred improved overall survival in comparison with a p16-negative status. CONCLUSIONS: The median age at diagnosis for HPV-related OPSCC is increasing as the proportion of OPSCCs caused by HPV rises among older adults. The favorable survival conferred by an HPV-positive tumor status persists in older adults. Cancer 2018;124:2993-9. © 2018 American Cancer Society.

Treatment preferences in human papillomavirus-associated oropharyngeal cancer.

The population of survivors with human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV-OPSCC) is rising. The improved prognosis of this etiologic subset is reflected in new staging guidelines as well as ongoing deintensification trials aiming to preserve excellent survival while decreasing treatment-related toxicities. However, as staging criteria and treatment standards evolve in the era of transoral surgery and deintensification, little is known regarding the needs and treatment preferences of patients with HPV-OPSCC. Herein, the current knowledge regarding treatment preferences and priorities, quality of life and concerns among patients with HPV-OPSCC is reviewed.

Patient Experience of Head and Neck Surgery With Free Flap Reconstruction.

Importance: Major head and neck surgery with microvascular free tissue transfer reconstruction is complex, with considerable risk of morbidity. Little is known about patients' experiences, including decision-making prior to, and regret following, free flap surgery. Objective: To characterize patient experiences and decision regret of patients undergoing head and neck reconstructive free flap surgery. Design, Setting, and Participants: This mixed-methods cohort study comprising semistructured interviews was conducted June to August 2021 at a single tertiary academic cancer center. Participants underwent head and neck reconstructive surgery with microvascular free tissue transfer (flap) more than 3 months before recruitment (range, 3 months to 4 years). Interview transcripts were qualitatively analyzed for themes. Participants also completed a Decision Regret Scale questionnaire. Exposure: Microvascular free flap surgery for head and neck reconstruction. Main Outcomes and Measures: Thematic analysis of interviews, decision regret score. Results: Seventeen participants were interviewed. Median (IQR) age was 61 (52-70) years. Overall, 7 participants were women (49%), and 10 of 17 were men (59%). The most common free flap was fibula (8/17, 47%). Three major themes with 9 subthemes were identified: theme 1 was the tremendous effect of preoperative counseling on surgical decision-making and satisfaction, with subthemes including (1) importance of clinical care team counseling on decision to have surgery; (2) emotional context colors preoperative understanding and retention of information; (3) expectation-setting affects satisfaction with preoperative counseling; and (4) desire for diversified delivery of preoperative information. Theme 2 was coexisting and often conflicting priorities, including (1) desire to survive above all else, and (2) desire for quality of life. Theme 3 was perception of surgery as momentous and distressing, including (1) surgery as a traumatic event; (2) centrality of mental health, emotional resolve, and gratitude to enduring surgery and recovery; and (3) sense of accomplishment in recovery. On the Decision Regret Scale, most participants had no regret (n = 8, 47%) or mild regret (n = 5, 29%); 4 had moderate-to-severe regret (24%). Conclusions and Relevance: In this mixed-methods cohort study, patient experiences surrounding major head and neck reconstructive free flap surgery were described. Opportunities to improve support for this complex and vulnerable population, and to mitigate decision regret, were identified.

Epidemiologic distinctions between base of tongue and tonsil oropharyngeal carcinomas.

BACKGROUND: Human papillomavirus (HPV)-positive tonsil and base of tongue (BOT) cancers have been considered together. However, important differences may exist. METHODS: Demographic and tumor characteristics, and survival, were compared by oropharyngeal cancer subsite from 2004 to 2016 in the National Cancer Database (NCDB). Trends in tonsillectomy from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 were examined. RESULTS: HPV-positive BOT (N = 13 081) were older than HPV-positive tonsil patients (N = 16 874; mean 61.5 vs. 58.4 years, p < 0.001), and individuals 70+ years were significantly more likely to have BOT tumors compared with individuals <50 (adjusted odd ratio [aOR] = 2.9, 95% confidence interval = 2.6-3.2). BOT patients were also more likely to be white, male, and have advanced tumor classification. Among 7418 NHANES participants, tonsillectomy was associated with older age and white race. CONCLUSIONS: There are epidemiologic and tumor-related differences among HPV-positive tonsil and BOT carcinomas. Demographic differences may be attributable to tonsillectomy trends.

Otolaryngology burden of disease and surgical case triage in resource-limited settings: An example from Cameroon.

OBJECTIVES: Otolaryngology services worldwide faced an unprecedented demand for case triage during the SARS-CoV-2 pandemic. We propose and apply a novel case-leveling schema in a resource-limited setting. Describing the surgical burden of otolaryngologic disease in this setting may critically inform resource planning to address global surgical disparities. METHODS: This is a retrospective study of otolaryngology cases performed over a 28-month period (1/2016-4/2018) at a hospital in rural Cameroon. Case details were collated and categorized as a surrogate measure of otolaryngologic disease in resource-limited settings. A case-levelling schema based on temporal urgency and anticipated impact on health was proposed and applied. RESULTS: 1277 cases took place during the study. The largest proportion of cases were head and neck (517, 40%), followed by pediatrics (316, 25%). A four-tiered leveling system was generated: level 1 cases were immediately life-saving; level 2 cases were expected to result in a significant return to functions of daily living, or would prevent future death from cancer; level 3 cases aimed to significantly improve quality of life; level 4 cases were purely elective. Upon application of the schema, most cases were deemed to be level 2 (661, 52%). CONCLUSION: We use our experience in a resource-limited setting to generate and apply a novel schema to be used for otolaryngology case triage in services facing unprecedented states of emergency such as the SARS-CoV-2 pandemic. This is the first study describing the surgical otolaryngologic disease burden in a resource-limited setting, data which may be used for future resource allocation. LEVEL OF EVIDENCE: 4.

Factors and Outcomes Associated With Temporal Bone Resection for Primary Parotid Malignancy.

OBJECTIVE(S): Although parotid cancer invading into the temporal bone makes up only a small fraction of all parotid cancers, it is more common and relatively understudied compared with primary cancer of the external auditory canal. The objective of this study was to determine what factors are associated with receiving parotidectomy with temporal bone resection (TBR) and the immediate postoperative outcomes. METHODS: We reviewed the National Cancer Database (2004-2015) for patients with primary parotid malignancy who received parotidectomy with or without TBR. Patient demographic, clinical, and perioperative variables were collected and then compared. Multivariate logistic regression was performed to determine factors associated with receiving TBR. RESULTS: We identified 134 patients who received parotidectomy with TBR and 16,595 who received parotidectomy only. Reported in terms of odds ratios (95% confidence interval), our multivariate model showed having surgery at an academic facility (1.91 [1.34-2.71], P < .001), clinical stage III or IV (7.48 [1.65-33.96] and 31.37 [7.61-129.32], P = .009 and P < .001, respectively), histologic grade II to IV (4.36 [1.51-12.57], 4.31 [1.53-12.15], and 6.74 [2.26-20.13], P = .006, .006, and .001, respectively), and adenoid cystic histology (3.23 [2.02-5.17], P < .001) were significantly and independently associated with receiving TBR. There was no significant difference in 30-day readmission, or 30-day or 90-day mortality, but the rate of positive surgical margins was significantly higher in those who underwent TBR. CONCLUSION: Demographic variables are not significant factors for receiving TBR. Tumor characteristics, such as clinical stage and histologic type, and receiving surgical treatment at an academic facility were more strongly associated with receiving TBR. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E2461-E2468, 2021.

Development of a web-based, patient-centered decision aid for oropharyngeal cancer treatment.

OBJECTIVES: Many patients diagnosed with oropharyngeal squamous cell carcinoma (OPSCC) have the option of radiation- or surgery-based therapy, and would benefit from a treatment decision aid (DA) to make decisions congruent with their personal values. Our objective was to develop a patient-centered DA for patients with OPSCC that is comprehensible, usable, acceptable, and well-designed. MATERIALS AND METHODS: Decisional needs from a pilot study of OPSCC survivors and treating physicians were used to inform a web-based prototype DA. A multidisciplinary steering group developed and iteratively revised the DA. Feasibility testing was conducted in two cycles to assess perspectives of stakeholders (medical, radiation and surgical oncologists, patient education experts, and OPSCC survivors). Survey data and open-ended responses were used to evaluate and refine the DA. RESULTS: 16 physicians, 4 patient education experts, and 6 survivors of OPSCC evaluated a web-based DA prototype in two cycles of testing. Participant feedback was used to revise the DA content and design between cycles. The majority of participants across both cycles indicated that the DA was comprehensible (97%), usable (86%), acceptable (78%), and well-designed (93%). Approximately three quarters of respondents indicated that they would use or share the DA in clinical practice. CONCLUSION: We developed the first patient-centered treatment decision aid (DA) designed for patients with OPSCC, to our knowledge. The DA was perceived favorably by stakeholders, with more than three quarters of respondents indicating they would use it in clinical practice. This tool may improve clinical practice as an adjunct to shared decision-making for OPSCC.

Treatment decision-making among patients with oropharyngeal squamous cell cancer: A qualitative study.

Oropharyngeal squamous cell cancer (OPSCC) is now the most common site of head and neck squamous cell cancer. Despite the focus on treatment deintensification in clinical trials, little is known about the preferences, experiences and needs of patients with OPSCC when deciding between surgery and radiation therapy as primary treatment with curative intent. In this qualitative study, pre-treatment and post-treatment oropharyngeal cancer patients were recruited to take part in one-on-one interviews (n = 11 pre-treatment) and focus group discussions (n = 15 post-treatment) about treatment decision-making. Recordings were transcribed and assessed for emergent themes using framework analysis. From the one-on-one interviews and focus group discussions with OPSCC patients, fourteen themes were identified. Participants expressed alarm at diagnosis, decisional conflict, and a variety of roles in decision-making (physician-controlled, shared, and autonomous). Decisions were driven by the perceived recommendation of the treatment team, a desire for physical (surgical) tumor removal, fear of adverse effects of treatment, and patient-specific values. Although participants felt well-informed by their treating physicians, they identified a need for additional patient-centered information. Participants were critical of the poor quality of information available on the internet, and acknowledged the advantage of hearing the experiences of post-treatment patients. The experiences identified herein may be used to guide patient-centered communication during patient counseling and to inform interventions designed to support patients' needs at diagnosis, ultimately helping to implement high-quality, patient-centered care.

Predictive value of olfactory impairment for cognitive decline among cognitively normal adults.

OBJECTIVE: Dementia affects over 47 million people worldwide. Olfactory impairment (OI) is a well-established predictive marker of conversion to dementia among those with mild cognitive impairment. This systematic review aims to describe the predictive value of OI for future cognitive decline among cognitively normal adults. METHODS: A literature search encompassing PubMed, EMBASE, and Cochrane for longitudinal cohort studies following cognitively normal adults with baseline OI in comparison to those without OI reporting incident cognitive impairment or dementia was included. Study design, participant demographics, olfactory testing method, and incidence of cognitive decline or dementia were abstracted. Two investigators independently reviewed all articles. RESULTS: The search yielded 964 nonduplicate abstracts and titles, from which 19 full-text articles were reviewed and 10 were included. Studies included were all good quality (mean score 8.7 of 9), and all studies (100%) found a statistically significant association between baseline OI and incident cognitive decline compared with normosmic controls. CONCLUSION: The existing literature suggests that OI predicts future cognitive decline among cognitively normal adults, supporting olfactory evaluation as a low-cost, minimally invasive, and widely available screening tool to be used in combination with other tests to identify adults at early risk of dementia. LEVEL OF EVIDENCE: NA Laryngoscope, 130:840-847, 2020.

HPV-positive Squamous Cell Carcinoma of the Larynx, Oral Cavity, and Hypopharynx: Clinicopathologic Characterization With Recognition of a Novel Warty Variant.

Human papillomavirus (HPV) is a principal driver for most oropharyngeal squamous cell carcinomas (OPSCCs), where it is strongly associated with improved survival. HPV is much less frequently detected in squamous cell carcinomas arising in nonoropharyngeal sites (non-OPSCCs), and its pathogenic role and prognostic value in these tumors is unclear. We evaluated the clinicopathologic features of 52 non-OPSCCs considered HPV-positive based upon p16 immunohistochemistry and direct HPV detection using RNA in situ hybridization (ISH), DNA ISH, or real-time DNA polymerase chain reaction. The HPV-positive non-OPSCCs were from the larynx (n=27), oral cavity (n=21), and hypopharynx (n=4). While most cases (n=34, 65%) showed classic histologic features of HPV-positive OPSCC, including endophytic growth, minimal keratinization, and hyperchromatic nuclei without koilocytic changes, a subset (n=13, 25%) were characterized by exophytic growth, exuberant surface hyperkeratosis and parakeratosis, marked nuclear pleomorphism, and prominent koilocytic atypia. These antithetical features were highly reminiscent of the warty variant of HPV-positive squamous cell carcinoma described in anogenital sites. Compared with tumors without warty features, the warty tumors presented at lower stage and were not associated with lymph node metastasis, local recurrence, or distant spread (4 y disease-free survival of 100% vs. 66%, P=0.069). The presence of transcriptionally active HPV as detected by RNA ISH suggests a pathogenic role for HPV in these nonoropharyngeal sites. While most HPV-positive non-OPSCCs are morphologically similar to their tonsillar counterparts, this study highlights a previously unrecognized warty variant that may be associated with a highly favorable clinical outcome.

Risk factors for human papillomavirus-positive nonoropharyngeal squamous cell carcinoma.

BACKGROUND: Human papillomavirus (HPV)-positive oropharyngeal cancer (HPV-OPC) is distinct from HPV-unassociated head and neck cancer. However, whether risk factors for HPV-positive oropharyngeal and nonoropharyngeal squamous cell cancer are the same is unclear. METHODS: Incident cases of HPV-positive head and neck cell cancer and matched non-cancer controls were enrolled in a multi-institutional, prospective study examining risk factors, biomarkers, and survival. RESULTS: HPV-nonOPC (n = 20) were more likely to be ever smokers than controls (n = 80, OR 3.49, 95%CI 1.11-10.9) and HPV-OPC (n = 185, OR 3.28, 95%CI 1.10-10.2). Compared with HPV-OPC, HPV-nonOPC were less likely to have had over 3 oral sexual partners (OR 0.29, 95%CI 0.06-0.9), more likely to have multimorbidity (OR 3.30, 95%CI 1.04-10.5), and less likely to have antibodies to HPV16 E6 (90% vs 28%, OR 0.05, 95%CI 0.02-0.2). HPV-nonOPC had worse 4-year OS (77% vs 96%, P = .001) and RFS (69% vs 94%, P < .001) than HPV-OPC. CONCLUSIONS: HPV-positive nonoropharyngeal are distinct from HPV-positive oropharyngeal cancers.

The association between diabetes and olfactory impairment in adults: A systematic review and meta-analysis.

BACKGROUND: Evidence suggests that olfactory impairment (OI) may be a degenerative neurologic complication of diabetes; however, the association is not yet well established. The objective of this work was to systematically review existing literature on the association between diabetes and OI in adults, with meta-analysis of evaluable studies. METHODS: A literature search encompassing 358 abstracts from the last 75 years in PubMed, EMBASE, and Cochrane was performed. English-language articles investigating adults with diabetes and OI in comparison to control groups with original data and ≥7 subjects were included. The Newcastle-Ottawa scale was applied for quality assessment. Two investigators independently reviewed all articles. For meta-analysis, the odds ratio of OI in diabetes compared with control groups was calculated using the fixed effects model. RESULTS: The initial search yielded 358 abstracts, from which 21 articles were reviewed and 11 articles (n = 6,747) were included. Studies included were case-control (64%) or cross-sectional (36%) with evidence level 3b. On the Newcastle-Ottawa scale, the mean quality assessment score for case-control and cross-sectional studies was 7.4 (maximum of 9) and 7.0 (maximum of 10), respectively. A statistically significant association between diabetes and olfaction compared with controls was found in 6 (55%) of the 11 articles. Four studies were eligible for meta-analysis, which yielded an overall odds of having OI with diabetes as 1.58 times more likely than in control groups (95% CI [1.16, 2.16]; I 2 = 10.3%). CONCLUSIONS: The reviewed studies support a significant association between diabetes and OI. Further studies are warranted to characterize this association. LEVEL OF EVIDENCE: 3a.

Priorities of human papillomavirus-associated oropharyngeal cancer patients at diagnosis and after treatment.

INTRODUCTION: Little is known regarding how human papillomavirus-positive oropharyngeal cancer (HPV-OPC) patient goals change with treatment. This study evaluates whether patient ranking of non-oncologic priorities relative to cure and survival shift after treatment as compared to priorities at diagnosis. MATERIALS AND METHODS: This is a prospective study of HPV-OPC patient survey responses at diagnosis and after treatment. The relative importance of 12 treatment-related priorities was ranked on an ordinal scale (1 as highest). Median rank (MR) was compared using Wilcoxon matched-pairs signed-rank tests. Prevalence of high concern for 11 treatment-related issues was compared using paired t-test. The effect of patient characteristics on change in priority rank and concern was evaluated using linear regression. RESULTS: Among 37 patients, patient priorities were generally unchanged after treatment compared with at diagnosis, with cure and survival persistently ranked top priority. Having a moist mouth uniquely rose in importance after treatment. Patient characteristics largely did not affect change in priority rank. Concerns decreased after treatment, except concern regarding recurrence. DISCUSSION: Treatment-related priorities are largely similar at diagnosis and after treatment regardless of patient characteristics. The treatment experience does not result in a shift of priorities from cure and survival to non-oncologic domains over cure and survival. The rise in importance of moist mouth implies that xerostomia may have been underappreciated as a sequelae of treatment. A decrease in most treatment-related concerns is encouraging, whereas the persistence of specific areas of concern may inform patient counseling.

Sex differences in HPV immunity among adults without cancer.

The incidence of human papillomavirus (HPV)-associated head and neck cancers is rising, particularly among men. Whether observed epidemiological differences in sex are explained by differences in sexual exposure and/or by immune response is unclear. In this cross-sectional, multi-institutional study, seroprevalence of antibodies to HPV L1 capsid antigen was compared by patient characteristics among 374 adult patients without cancer. A significantly higher seroprevalence was observed among women compared with men for HPV16 (OR = 2.96, 95% CI = 1.21-7.21) and HPV18 (OR = 2.84, 95% CI = 1.06-7.60) L1 antibodies. This difference persisted for HPV16 after controlling for lifetime and recent sexual behavior. After controlling for sex, HPV16 and HPV18 L1 seroprevalence was also significantly associated with higher number of lifetime (HPV16 OR = 1.05, 95% CI = 1.01-1.08; HPV18 OR = 1.04, 95% CI = 1.01-1.08) and recent (HPV16 OR = 1.54, 95% CI = 1.15-2.07; HPV18 OR = 1.40, 95% CI = 1.07-1.82) oral but not vaginal sexual partners. These findings potentially suggest a more robust immune response to HPV16/18 among women compared with men that may not be explained by differences in number of sexual partners, and thereby presumably HPV exposure. The independent association of HPV16/18 L1 seroprevalence with higher number of oral sexual partners suggests a possible role for site of mucosal exposure in the HPV immune response.

Case report: presentation of delayed tracheal perforation after hemithyroidectomy.

Hemithyroidectomy is a low-risk, outpatient procedure commonly performed for benign and some small, differentiated thyroid malignancies. Delayed tracheal perforation following thyroid surgery is exceedingly rare and has previously only been reported after total thyroidectomy. We describe a 25-year-old patient who underwent an unremarkable right hemithyroidectomy to remove a 4-centimeter fine needle aspiration cytologically indeterminate thyroid nodule, and presented 4 weeks later with acute anterior neck swelling and subcutaneous emphysema after strenuous exercise. Computed tomography showed pockets of air tracking along a right lateral tracheal wall irregularity on the operative side. Flexible tracheobronchoscopy identified a corresponding pinhole-sized defect. A bedside neck exploration was performed with drain placement. The patient was restricted to limited activity for 4 weeks, and recovered uneventfully. Surgeons who perform thyroid surgery must be aware of the possibility of delayed tracheal perforation after hemithyroidectomy. Conservative management may be appropriate for the stable patient.