Paraganglioma and other tumour detection rates in individuals with SDHx pathogenic variants by age of diagnosis and after the age of 50.

OBJECTIVE: Patients with SDHx germline mutations (SDHA, AF2, B, C, D) are at risk for paragangliomas (PGLs), renal cell carcinoma and gastrointestinal stromal tumours. The aim of this study was to evaluate the age of SDHx tumour diagnosis in those with pathogenic variants (PVs), notably tumour detection after the age of 50 years. STUDY DESIGN: Longitudinal retrospective observational analysis. PATIENTS: Individuals with SDHx PVs. MEASUREMENTS: Demographic, clinical, genetic, screening and tumour detection and treatment data were abstracted from the electronic medical record. Descriptive analysis was utilised. RESULTS: A total of 165 patients with SDHx PVs from 34 families were evaluated. Sixty-eight patients (41.2%) had at least one known SDHx-related tumour in their history, identified through symptoms, screening or incidentally. The average age of SDHx-related tumour diagnosis was 32.0 years. Age of diagnosis varied by the gene. Nine patients (n = 50; 18.0%) were identified with a tumour after the age of 50, identified via baseline screening after PV identification, or due to symptoms before molecular SDHx diagnosis. CONCLUSIONS: Though tumours were identified in individuals above the age of 50; they were all identified on baseline screening or due to symptoms, confirming that baseline screening is essential. Given the slow-growing nature of PGLs, these tumours might have been discovered before age 50 if molecular diagnosis and baseline screening had occurred earlier. Considering discontinuing screening after age 50 may be warranted if baseline screen imaging is negative and the individual does not have a prior tumour history.

Tumor detection rates in screening of individuals with SDHx-related hereditary paraganglioma-pheochromocytoma syndrome.

PURPOSE: Minimal data exist regarding the efficacy of screening protocols for individuals with SDHx germline pathogenic variants with hereditary paraganglioma-pheochromocytoma syndrome. This study aimed to evaluate the SDHx-related tumor detection rate in individuals undergoing clinical screening protocols. METHODS: A multicenter retrospective longitudinal observational study was conducted. Individuals with germline SDHx pathogenic variants underwent clinical whole-body imaging and biochemical testing. RESULTS: Two hundred sixty-three individuals with SDHx germline pathogenic variants completed 491 imaging screens. Individuals with SDHB germline pathogenic variants were most common (n = 188/263, 72%), followed by SDHD (n = 35/263, 13%) and SDHC (n = 28/263, 11%). SDHx-related tumors were found in 17% (n = 45/263) of the cohort. Most SDHx-related tumors were identified on baseline imaging screen (n = 39/46, 85%). Individuals with SDHD pathogenic variants had the highest tumor detection rate (n = 14/35, 40%). Of imaging screens identifying SDHx-related paraganglioma/pheochromocytoma, 29% (n = 12/41) had negative biochemical testing. Secondary actionable findings were identified in 15% (n = 75/491) of imaging screens. CONCLUSION: Current SDHx screening protocols are effective at identifying SDHx-related tumors. Tumor detection rates vary by SDHx gene and screening has the potential to uncover actionable secondary findings. Imaging is an essential part of the screening process as biochemical testing alone does not detect all disease.

Distress Management, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology.

Distress is defined in the NCCN Guidelines for Distress Management as a multifactorial, unpleasant experience of a psychologic (ie, cognitive, behavioral, emotional), social, spiritual, and/or physical nature that may interfere with the ability to cope effectively with cancer, its physical symptoms, and its treatment. Early evaluation and screening for distress leads to early and timely management of psychologic distress, which in turn improves medical management. The panel for the Distress Management Guidelines recently added a new principles section including guidance on implementation of standards of psychosocial care for patients with cancer.

Orbital invasion routes of non-melanoma skin cancers and survival outcomes.

PURPOSE/OBJECTIVES: Overall non-melanoma head and neck skin cancer has a good prognosis; however, rarely patients have an aggressive variant which results in orbital invasion via perineural spread or direct extension. Despite these consequences, there are limited published studies defining this clinical entity. The main objectives of the current study are to describe orbital invasion patterns of non-melanoma head and neck skin cancers and their impact on survival. METHODS: Retrospective case series from a tertiary-care, academic institution performed between 2004 and 2014. Demographic and tumour characteristics are reported as well as patterns of orbital invasion, types of treatments received, and survival outcomes. RESULTS: There were 17 consecutive patients with non-melanoma skin cancer and orbital invasion who met inclusion criteria. Average age at orbital invasion diagnosis was 70.8 years old. 76% were male. Mean follow-up time was 28.5 months. Of these patients, 71% had squamous cell carcinoma and 29% had basal cell carcinoma. Brow (41%) was the most common primary sub-site followed by cheek (23%) and temple (12%). 76% of patients had a history of prior treatment. The lateral orbital wall (41%) was the most common site of invasion, followed by the medial orbital wall (29%) and antero-superior invasion (23%). Age, histology, and location of orbital invasion were associated with disease-specific and overall survival. CONCLUSION: Orbital invasion for non-melanoma head and neck skin cancers creates a treatment dilemma and the patterns of invasion are described. In addition, the location of orbital invasion is associated with survival outcomes.

Early ambulation after fibular free flap surgery is associated with reduced length of stay, increased mobility independence, and discharge to home.

BACKGROUND: Fibula free flaps (FFF) are one of the most common bony flaps utilized. This paper describes a quality improvement project aimed at increasing early ambulation. METHODS: A review of FFF patients at an academic hospital was completed (2014-2023). In 2018, an institutional change to encourage early ambulation without placement of a boot was made. Changes in hospital disposition and physical therapy outcomes were evaluated. RESULTS: A total of 168 patients underwent FFF reconstruction. There was a statistically significant lower length of stay in Group 2 (early ambulation, no boot) (8.1 vs. 9.4; p = 0.04). A higher rate of discharge to a skilled nursing facility was noted in Group 1 (delayed ambulation with boot) (21.3% vs. 11.9%; p = 0.009). A higher proportion of patients in Group 2 demonstrated independence during bed mobility, transfers, and gait (p < 0.05). CONCLUSIONS: Early ambulation without boot placement after FFF is associated with decreased length of hospital stay, improved disposition to home and physical therapy outcomes.

Distress management.

The integration of psychosocial care into the routine care of all patients with cancer is increasingly being recognized as the new standard of care. These NCCN Clinical Practice Guidelines in Oncology for Distress Management discuss the identification and treatment of psychosocial problems in patients with cancer. They are intended to assist oncology teams identify patients who require referral to psychosocial resources and to give oncology teams guidance on interventions for patients with mild distress to ensure that all patients with distress are recognized and treated.

Correlates of elevated distress thermometer scores in breast cancer patients.

PURPOSE: Distress is prevalent in breast cancer patients and can be detrimental to quality of life, performance status, treatment adherence, and satisfaction with medical care. The National Comprehensive Cancer Network developed the distress thermometer (DT) as a self-assessment tool for screening distress in cancer patients. Given time and financial constraints, it is important to refine screening criteria to identify patients with elevated risk for distress. In this study, we identify clinical and epidemiological factors that are associated with an increased likelihood of elevated DT scores (≥ 4 and ≥ 7). METHODS: We assessed 229 female patients with the DT at their initial consultation for breast cancer at the Huntsman Cancer Hospital between September 2007 and December 2008. Descriptive statistics and logistic regression models were used to analyze DT and patient data. RESULTS: Patients undergoing their initial distress thermometer screening within 30 days of receiving a diagnosis of breast cancer had the highest likelihood of scoring ≥ 4 and ≥ 7 on the DT screening tool. Emotional and physical concerns were associated with scores ≥ 4 and scores ≥ 7. Spiritual concerns became significant in patients reporting scores ≥ 7. Patients who were non-Caucasian, unemployed, had a prior history of depression, presented for recurrent disease, or who had been recently diagnosed had a higher likelihood of scores ≥ 4 and scores ≥ 7. CONCLUSIONS: Four groups of patients should be targeted for aggressive screening; patients with a prior diagnosis of depression, patients presenting with recurrent disease, unemployed patients, and non-Caucasian patients. Interventions should address physical, emotional, and spiritual concerns.

Rare skin malignancies of the head and neck: a review.

The skin of the head and neck is a common location for skin cancers to develop. The majority of skin cancers of the head and neck are basal cell and squamous cell carcinomas, with melanoma also occurring at a significant incidence. However, there are many other histologies that occur and raise diagnostic and treatment challenges. In this article, we review some of the more common histologies that are classified as rare skin malignancies of the head and neck. Specifically, epidemiology, pathogenesis, histopathology, and treatment options for each of these histologies will be discussed. There is a growing emphasis on Mohs micrographic surgery in the treatment of these lesions, although, some are not amenable to this technique. A multidisciplinary approach is frequently useful in their treatment.

Skin cancers of the external auditory canal.

Skin cancers of the external auditory canal are rare tumors treated by a variety of medical and surgical specialties. Treatment of skin cancer is generally successful; however, tumors involving this anatomic location can be aggressive and require a multidisciplinary approach to treatment. This multidisciplinary review provides facial plastic surgeons, caring for these patients, an updated approach to cancers of the external auditory canal focusing on findings that may indicate more aggressive disease and warrant expanded workup and treatment.

The Natural History of Observed SDHx -Related Head and Neck Paragangliomas Using Three-Dimensional Volumetric Tumor Analysis.

OBJECTIVE: Characterize the natural history and clinical behavior of head and neck paragangliomas (HNPGLs) in subjects with succinate dehydrogenase ( SDHx ) pathogenic variants using volumetric tumor measurements. STUDY DESIGN: Cohort study. SETTING: Tertiary academic referral center. PATIENTS: Subjects with SDHx HNPGLs under observation for at least 6 months with 2 or more magnetic resonance imaging or computed tomography scans. INTERVENTIONS: Diagnostic interventions include next-generation sequencing, magnetic resonance imaging, and computed tomography. Therapeutic interventions include microsurgical resection or stereotactic radiosurgery. MAIN OUTCOME MEASURES: Radiographic progression was defined as a 20% or greater increase in volume. Cranial nerve (CN) functional outcomes were assessed using clinical documentation. RESULTS: A total of 19 subjects with 32 tumors met the inclusion criteria. Median radiographic follow-up was 2.2 years, and the median volumetric growth rate was 0.47 cm 3 /yr. Kaplan-Meier estimated rates of survival free of radiographic progression for all SDHx tumors at 1, 2, and 3 years were 69, 50, and 22%, respectively. No tumors developed new CN palsies during the period of observation. CONCLUSIONS: Over intermediate-term follow-up, observation of treatment-naive SDHx -related HNPGLs did not result in new cranial neuropathy. Although indefinite observation is only appropriate for select cases, these data support an interval of observation to characterize growth rate in asymptomatic to minimally symptomatic patients, who are at high risk of treatment-related morbidity. Given the early age at diagnosis and high risk of bilateral multifocal phenotypes in SDHx HNPGL mutation carriers, these data may aid in optimizing patient tumor control and CN functional preservation. Further studies are necessary to determine whether pretreatment growth rate is correlated with clinical outcomes.

A need to tailor surveillance based on family history: describing a highly penetrant familial paraganglioma kindred with an SDHD pathogenic variant.

Pathogenic variants (PVs) in the SDHD gene increase risk for paragangliomas (PGL)/pheochromocytomas, renal cell carcinomas, and gastrointestinal stromal tumors. Penetrance in individuals with SDHD PVs varies in reported research from 40-70%, and there is limited evidence of specific genotype risks. This study aims to characterize a multi-generational family with SDHD p.Trp43* PVs and potential genotype-phenotype considerations for surveillance. Individuals with a paternally inherited SDHD p.Trp43*(c.129G > A) PV were identified. Genetic, medical and family histories were abstracted, including clinical characteristics, tumor histories, and treatment approaches. Eleven individuals with the SDHD PV in the same kindred were diagnosed with 41 SDHx-related tumors across all family members. Eight individuals developed 27 head and neck PGL of varying origins, and seven individuals developed tumors outside of the head and neck region. Many individuals had multiple tumors, and age of first tumor diagnosis ranged from age 10 to age 45 years old. Individuals with SDHD p.Trp43* variants may have higher risks for SDHx related tumors than other SDHD variants. Prioritizing identification of at-risk individuals and initiating surveillance tailored to family history is recommended given the rate of multiple tumors found in one familial branch of individuals under 18 years old. Individuals with strong family histories of PGL at young ages with this PV will benefit from tailored surveillance recommendations.

Success of Implantable Doppler Probes for Monitoring Buried Free Flaps.

OBJECTIVE: The objective of this study is to describe the operative success of completely buried free flaps and to determine the safety/reliability of using implantable dopplers for postoperative monitoring in completely buried free flaps. STUDY DESIGN: A retrospective chart review was conducted from 2014 to 2020. Patients were included who had implantable dopplers placed for monitoring a completely buried free flap without a visible skin paddle. SETTING: Single academic cancer hospital. METHODS: Patient charts were reviewed to determine flap viability after surgery, need for reoperation, and ability of implanted doppler probes to detected change in free flap status. RESULTS: A total of 65 patients were included. Locations of flaps were as follows: pharynx, 76.9%; skull base, 7.7%; trachea, 6.2%; esophagus, 4.6%; and facial reanimation, 4.6%. Types of free flaps performed included radial forearm (50.8%), anterolateral thigh (44.6%), and gracilis (4.6%). One patient (1.5%) returned to the operating room for vascular compromise, which was accurately detected by the implantable doppler and salvaged. All free flaps were viable upon hospital discharge based on clinical examination and implantable doppler signals. There were no complications related to implantable doppler use. CONCLUSIONS: Implantable dopplers are an effective method for evaluating postoperative success of completely buried free flaps. In our series utilizing implantable dopplers, buried free flap survival was higher than traditionally thought. The use of implanted dopplers for monitoring buried free flaps allows for an effective, cosmetically appealing, and simplified reconstructive technique.

Trust in physicians among patients with head and neck cancer before and after treatment.

BACKGROUND: Little is known about physician trust in patients with head and neck cancer. This study's aim is to evaluate trust pre- and post-treatment. METHODS: A study was conducted of 50 patients with head and neck cancer at a tertiary referral center. Surveys administered before and after treatment included several validated survey tools including the Trust in Oncologist Scale Short Form. RESULTS: There was an increase in overall trust scores (p < 0.001). Female patients (p = 0.034) and those who received chemotherapy (p = 0.001) were less trusting post-treatment. Patients with more comorbidities (p = 0.045) and progression of disease (p = 0.029) had higher final trust than those without. Patients with high initial distress scores showed a decrease in trust (p = 0.023). CONCLUSIONS: Patients with head and neck cancer trust their surgeon more after completion of treatment, with specific characteristics having a variable impact on trust scores.

SPM Receptor Expression and Localization in Irradiated Salivary Glands.

Radiation therapy-mediated salivary gland destruction is characterized by increased inflammatory cell infiltration and fibrosis, both of which ultimately lead to salivary gland hypofunction. However, current treatments (e.g., artificial saliva and sialagogues) only promote temporary relief of symptoms. As such, developing alternative measures against radiation damage is critical for restoring salivary gland structure and function. One promising option for managing radiation therapy-mediated damage in salivary glands is by activation of specialized proresolving lipid mediator receptors due to their demonstrated role in resolution of inflammation and fibrosis in many tissues. Nonetheless, little is known about the presence and function of these receptors in healthy and/or irradiated salivary glands. Therefore, the goal of this study was to detect whether these specialized proresolving lipid mediator receptors are expressed in healthy salivary glands and, if so, if they are maintained after radiation therapy-mediated damage. Our results indicate that specialized proresolving lipid mediator receptors are heterogeneously expressed in inflammatory as well as in acinar and ductal cells within human submandibular glands and that their expression persists after radiation therapy. These findings suggest that epithelial cells as well as resident immune cells represent potential targets for modulation of resolution of inflammation and fibrosis in irradiated salivary glands.

Penetrating Trauma Rapid Estimated Disability Scale: Assessing Facial Self-Inflicted Gunshot Wounds.

Objectives: Self-inflicted facial gunshot wounds (GSWs) result in complex but consistent injuries that are often survivable. We suggest a novel method for rapid stratification into groups that may be associated with hospital course and cost after self-inflicted facial GSWs. Methods: This is retrospective review of self-inflicted facial GSWs between January 1, 2009, and December 31, 2018, at a tertiary academic center. Patients were given a penetrating trauma rapid estimated disablity (PRED) score (1-4) based solely on radiologic imaging injury patterns. Clinicopathologic factors were then compared between groups. Results: There were 2 PRED 1 patients (15.1%), 8 PRED 2 patients (29.6%), 5 PRED 3 patients (18.5%), and 12 PRED 4 patients (44.4%). An increased PRED score was statistically associated with increasing mean days in intensive care unit (2.5 PRED 1, 4.2 PRED 2, 6 PRED 3, 11.6 PRED 4, p = 0.001), mean length of hospitalization (5.5 PRED 1, 13.1 PRED 2, 25.6 PRED 3, 39.8 PRED 4, p = 0.007), and mean cost ($) of hospitalization (22,000 PRED 1, 29,000 PRED 2, 37,000 PRED 3, 63,000 PRED 4, p = 0.01). Conclusions and Relevance: The PRED score for self-inflicted GSWs to the face is strongly associated with length of hospital stay and cost of hospitalization.

Individualized prediction of late-onset dysphagia in head and neck cancer survivors.

BACKGROUND: Limited data exist regarding which head and head and neck cancer (HNC) survivors will suffer from long-term dysphagia. METHODS: From a population-based cohort of 1901 Utah residents with HNC and ≥3 years follow-up, we determined hazard ratio for dysphagia, aspiration pneumonia, or gastrostomy associated with various risk factors. We tested prediction models with combinations of factors and then assessed discrimination of our final model. RESULTS: Cancer site in the hypopharynx, advanced tumor classification, chemoradiation, preexisting dysphagia, stroke, dementia, esophagitis, esophageal spasm, esophageal stricture, gastroesophageal reflux, thrush, or chronic obstructive pulmonary disease were associated with increased risk of long-term dysphagia. Our final prediction tool gives personalized risk calculation for diagnosis of dysphagia, aspiration pneumonia, or gastrostomy tube placement at 5, 10, and 15 years after HNC based on 18 factors. CONCLUSION: We developed a clinically useful risk prediction tool to identify HNC survivors most at risk for dysphagia.

Characterization of Malignant Head and Neck Paragangliomas at a Single Institution Across Multiple Decades.

Importance: Malignant head and neck paragangliomas (HNPGLs) are rare entities, and there are limited data regarding optimal treatment recommendations to improve clinical outcomes. Objective: To classify succinate dehydrogenase (SDH) germline mutations associated with malignant HNPGLs, evaluate time from diagnosis to identification of malignant tumor, describe locations of metastases and the functional status of malignant HNPGLs, and determine the role of selective neck dissection at the time of initial surgical resection. Design, Setting, and Participants: A retrospective cohort study was completed of patients diagnosed with paragangliomas on various sites on the body at an academic tertiary cancer hospital between the years 1963 and 2018. A subanalysis of HNPGLs was also completed. Data regarding diagnosis, gene and mutation, tumor characteristics and location, and treatments used were reviewed between February 2017 and March 2018. Main Outcomes and Measures: Mutations of SDH genes associated with benign and malignant HNPGLs, treatments used, time to the discovery of malignancy, and location of metastasis. Results: Of the 70 patients included in the study, 40 (57%) were male, and the mean (SD) age was 47 (21.1) years. Of patients with tumors isolated to the head and neck, 38 (54%) had benign HNPGLs, which were associated with mutations in the genes SDH subunit B (SDHB) (n = 18; 47%), SDH subunit C (n = 2; 5%), and SDH subunit D (n = 18; 47%). Among those with malignant HNPGLs, all but 1 patient had mutations in SDHB (n = 5; 83%); 1 patient had no mutation associated with their disease. The average age at diagnosis for malignant HNPGLs was 35 years, while benign tumors were diagnosed at an average age at 36 years. All patients with malignant disease underwent surgery. Four patients were found to have metastasis at the time of selective neck dissection. Among patients with malignant HNPGLs, 5 (83%) were treated with adjuvant radiation, and 1 (17%) was treated with adjuvant chemotherapy. Conclusions and Relevance: Malignant HNPGLs are rare entities that are difficult to diagnose and are typically identified by the presence of regional or distant metastasis. The results of this study found the prevalence of malignant HNPGLs to be 9%. These data suggest that it is beneficial to perform a selective neck dissection at the time of tumor excision. All patients with malignant HNPGLs but 1 had SDHB mutations.

Rates of Dysphagia-Related Diagnoses in Long-Term Survivors of Head and Neck Cancers.

OBJECTIVE: To estimate long-term prevalence of new dysphagia-related diagnoses in a large cohort of head and neck cancer survivors. STUDY DESIGN: Retrospective cohort. SETTING: Population based. SUBJECTS AND METHODS: In total, 1901 adults diagnosed with head and neck cancer between 1997 and 2012 with at least 3 years of follow-up were compared with 7796 controls matched for age, sex, and birth state. Prevalence of new dysphagia-related diagnoses and procedures and hazard ratio compared to controls were evaluated in patients 2 to 5 years and 5 years and beyond after diagnosis. Risk factors for the development of these diagnoses were analyzed. RESULTS: Prevalence of new diagnosis and hazard ratio compared to controls remained elevated for all diagnoses throughout the time periods investigated. The rate of aspiration pneumonia was 3.13% at 2 to 5 years, increasing to 6.75% at 5 or more years, with hazard ratios of 9.53 (95% confidence interval [CI], 5.08-17.87) and 12.57 (7.17-22.04), respectively. Rate of gastrostomy tube placement increased from 2.82% to 3.32% with hazard ratio remaining elevated from 51.51 (13.45-197.33) to 35.2 (7.81-158.72) over the same time period. The rate of any dysphagia-related diagnosis or procedure increased from 14.9% to 26% with hazard ratio remaining elevated from 3.32 (2.50-4.42) to 2.12 (1.63-2.75). Treatment with radiation therapy and age older than 65 years were associated with increased hazard ratio for dysphagia-related diagnoses. CONCLUSION: Our data suggest that new dysphagia-related diagnoses continue to occur at clinically meaningful levels in long-term head and neck cancer survivors beyond 5 years after diagnosis.

Adjuvant radiation for positive margins in adult head and neck sarcomas is associated with improved survival: Analysis of the National Cancer Database.

BACKGROUND: Adult head and neck (H&N) sarcomas are a rare malignancy with limited data delineating the role of postoperative radiotherapy (PORT), particularly for a positive surgical margin. There are no randomized trials supporting the use of PORT, therefore treatment trends vary between institutions. A positive margin predicts recurrence and poor survival outcomes. This study uses the National Cancer Database (NCDB) to investigate whether PORT improves overall survival (OS) in adult H&N sarcomas with a positive margin and how utilization has changed. METHODS: Patients (n = 1142) in the NCDB from 2004-2013 with adult H&N sarcomas who underwent resection and had a positive margin. RESULTS: Factors significantly associated with increased utilization of PORT were: having insurance, salivary gland primary site, high-risk histology, poor differentiation, and a macroscopic positive margin. Treatment with PORT was associated with improved 5-year OS for all patients with a positive margin (57% vs 48%; P = .002), both microscopic (57% vs 49%; P = .010) and macroscopic (57% vs 41%; P = .036). Improved OS was significant after controlling for other known covariates on multivariate analysis (HR: 0.76; [0.64-0.90]; P = .002). Treatment at a community-based facility was an independent predictor for reduced OS (HR: 1.37; [1.15-1.64]; P < .001). The percentage utilization (53%) of PORT for these patients did not change significantly over time. CONCLUSION: PORT provides a significant survival benefit for adult H&N sarcoma patients with either a microscopic or macroscopic positive margin; however, PORT is underutilized. Treatment at academic/research cancer programs was associated with increased utilization of PORT and improved survival outcomes.

Familial clustering of oropharyngeal squamous cell carcinoma in the Utah population.

BACKGROUND: The main purpose of the current study was to define the familial aggregation of oropharyngeal squamous cell carcinoma (SCC) and risk to relatives of patients with oropharyngeal SCC. METHODS: We conducted a retrospective study utilizing linked population-based genealogy and state cancer registry databases between 1966 and 2012. Relative risks for oropharyngeal SCC and other malignancies among patients with oropharyngeal SCC and their relatives were estimated. RESULTS: Significant excess pairwise relatedness was observed for oropharyngeal SCC diagnosed before age 65 years. Significant excess risk for oropharyngeal SCC was observed for first-degree relatives of patients. Relatives of oropharyngeal SCC patients also demonstrated elevated rates of multiple other malignancies, including both lung and cervical cancers. CONCLUSION: Relatives of patients with oropharyngeal SCC display elevated risks of oropharyngeal, lung, and cervical cancers among others, suggesting a possible shared genetic etiology involving tobacco-related and human papillomavirus (HPV)-related malignancies.