Human papillomavirus circulating tumor DNA assays as a mechanism for head and neck cancer equity in rural regions of the United States.

The rates of human papillomavirus-positive oropharyngeal cancer (HPV-OPC) are rising worldwide and in the United States, particularly in rural regions including Appalachia. Rural areas face unique health challenges resulting in higher cancer incidence and mortality rates, and this includes HPV-OPC. The recent advent of highly sensitive liquid biopsies for the non-invasive detection of HPV-OPC recurrence (circulating tumor HPV DNA, HPV ctDNA) has been swiftly adopted as part of surveillance paradigms. Though knowledge gaps persist regarding its use and clinical trials are ongoing, the ease of collection and cost-effectiveness of HPV ctDNA make it more accessible for HPV-OPC survivors than usual surveillance methods of frequent exams and imaging. Herein, we discuss how implementing HPV ctDNA assays in rural regions of the United States provide one poignant example of how liquid biopsies can improve cancer care equity.

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.

Evaluation of the Incidence of Human Papillomavirus-Associated Squamous Cell Carcinoma of the Sinonasal Tract Among US Adults.

This case series assesses the incidence of human papillomavirus (HPV)-associated sinonasal squamous cell carcinoma (SNSCC) and the prevalence of HPV-positive SNSCC among US adults.

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.

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.

Biologic and behavioral associations of estrogen receptor alpha positivity in head and neck squamous cell carcinoma.

OBJECTIVES: Tumor HPV status is an established independent prognostic marker for oropharynx cancer (OPC). Recent studies have reported that tumor estrogen receptor alpha (ERα) positivity is also associated with prognosis independent of HPV. Little is known about the biologic and behavioral predictors of ERα positivity in head and neck squamous cell cancer (HNSCC). We therefore explored this in a multicenter prospective cohort study. MATERIALS AND METHODS: Participants with HNSCC completed a survey and provided a blood sample. Tumor samples were tested for ERα using immunohistochemistry. ERα positivity was defined as ≥1%, standardized by the American Society of Clinical Oncology/College of American Pathologists in breast cancer. Characteristics were compared with χ2 and Fisher's exact test. Odds ratios (OR) were calculated using logistic regression. RESULTS: Of 318 patients with HNSCC, one third had ERα positive tumors (36.2%, n = 115). Odds of ERα expression were significantly increased in those with HPV-positive tumors (OR = 27.5, 95% confidence interval[CI] 12.1-62), smaller tumors (≤T2, OR = 3.6, 95% CI 1.9-7.1), male sex (OR = 2.0, 95% CI 1.1-3.6), overweight/obesity (BMI ≥ 25, OR = 1.9, 95% CI 1.1-3.3), and those married/living with a partner (OR = 1.7, 95% CI 1.0-3.0). In a multivariate model, HPV-positivity (aOR = 27.5, 95% CI 11.4-66) and small tumor size (≤T2, aOR = 2.2, 95% CI 1.0-4.8) remained independently associated with ERα status. When restricted to OPC (n = 180), tumor HPV status (aOR = 17.1, 95% CI 2.1-137) and small tumor size (≤T2, aOR = 4.0 95% CI 1.4-11.3) remained independently associated with ERα expression. CONCLUSION: Tumor HPV status and small tumor size are independently associated with ERα expression in HNSCC.

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.

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.

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.

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.

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.

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.

Impact of the COVID-19 pandemic on Otolaryngology trainee education.

BACKGROUND: The COVID-19 pandemic has reduced clinical volume with a negative impact on trainee education. METHODS: Survey study of Otolaryngology trainees in North America, during the COVID-19 pandemic in April 2020. RESULTS: Of 216 respondents who accessed the survey, 175 (83%) completed the survey. Respondents reported a universal decrease in clinical activities (98.3%). Among participants who felt their program utilized technology well, there were significantly decreased concerns to receiving adequate educational knowledge (29.6% vs 65.2%, P = .003). However, 68% of trainees still expressed concern in ability to receive adequate surgical training. In addition, 54.7% of senior trainees felt that the pandemic had a negative impact on their ability to secure a job or fellowship after training. CONCLUSIONS: Trainees universally felt a negative impact due to the COVID-19 pandemic. Use of technology was able to alleviate some concerns in gaining adequate educational knowledge, but decreased surgical training remained the most prevalent concern.

The Role of Age and Merkel Cell Polyomavirus in Oral Cavity Cancers.

The incidence of oral tongue cancer, the majority subsite of oral cavity cancer, is rising among young people with less exposure to tobacco and alcohol. Viral causes have been proposed, including Merkel cell polyomavirus (MCPyV). We evaluated patient and tumor characteristics among 126 incident oral cavity cancers (OCCs). Consistent with generational norms, younger patients had less exposure to tobacco and a greater number of oral sexual partners than older OCCs. In addition, younger patients were more likely to present at an earlier stage and with cancer arising from the oral tongue (each P < .05). A subset of 44 cases was centrally tested for MCPyV large T antigen expression by immunohistochemistry. In the presence of controls, none of the tumors expressed MCPyV. These findings exclude consideration of MCPyV as an etiologic factor in OCC and may generate hypotheses for future examinations of the factors underlying the rise in oral tongue cancers.

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.

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.

Distinct biomarker and behavioral profiles of human papillomavirus-related oropharynx cancer patients by age.

BACKGROUND: HPV-positive oropharynx squamous cell cancer (HPV-OPC) patients were initially described as younger, however incidence has increased among older age-groups. It is unknown why some patients present at a younger age and others at a later age. METHODS: Multi-institutional prospective study of HPV-OPC cases (n = 163) and matched controls (n = 345) with detailed behavioral survey, and serum tested for HPV antibodies by fluorescent bead-based technology. Age at diagnosis was used to stratify patients into younger (≤50 years), middle-age (51-65), and older (>65). RESULTS: By age, demographic characteristics were largely similar, but HPV biomarkers and sexual acts differed. Younger cases were more likely to be HPV16-positive than older cases (100% vs 77%, p = 0.009). Similarly, younger cases were more likely to be HPV16 E6 or E7 seropositive (100% vs 82%, p = 0.03). Younger cases had a higher number of oral sex partners per year, a marker of sexual intensity (sex-years, p = 0.003), but a similar number of lifetime oral sex partners (measure of cumulative sexual exposure), compared to older cases. While sex-years were higher for younger cases and controls, cases had significantly higher sex-years than matched controls in each age-group (p < 0.001). Younger patients were also more likely to perform oral sex at sexual debut, and were younger at sexual debut (each p < 0.03). CONCLUSIONS: Younger, middle-age and older HPV-OPC have distinct biomarker and behavioral profiles. Younger HPV-OPC cases have higher intensity of sexual exposure than older cases and controls, which may in part explain earlier disease onset. The distribution of HPV16-positive tumors among HPV-OPC differs by age group.

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.

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.