Kristen B. Pytynia

Epidemiology of HPV-associated oropharyngeal cancer

Squamous cell carcinoma of the oropharynx is increasing in incidence in epidemic proportion. This site specific increase in incidence is due to an increase in human papillomavirus (HPV)-related squamous cell carcinoma, while the incidence of tobacco related squamous cell carcinoma is decreasing. In particular, the incidence of HPV-related oropharyngeal squamous cell carcinoma (OPSCC) is increased among middle aged white men, and sexual behavior is a risk factor. HPV-related oropharyngeal squamous cell carcinoma represents a growing etiologically distinct subset of head and neck cancers with unique epidemiological, clinical, and molecular characteristics that differ from those of HPV-unassociated cancers. In this review, we discuss the epidemiology of HPV-related OPSCC, the prevalence of oral/oropharyngeal HPV infection, and efforts aimed at reducing the incidence of HPV-related OPSCC.

Matched-Pair Analysis of Survival of Never Smokers and Ever Smokers With Squamous Cell Carcinoma of the Head and Neck

PURPOSE To compare survival rates between patients with squamous cell carcinoma of the head and neck (SCCHN) without a history of smoking (never smokers) and those with a current or previous history of smoking (ever smokers). PATIENTS AND METHODS Fifty never smokers with newly diagnosed SCCHN were matched to 50 ever smokers according to sex, age, tumor site, overall stage, nodal stage, and treatment. Survival analysis was performed using Kaplan-Meier estimates. Matched-pair survival was compared using the Cox proportional hazards model. RESULTS The never smokers had a greater overall survival (P =.020), disease-specific survival (P =.022), and recurrence-free survival (P =.016). Furthermore, matched-pair analysis demonstrated smoking was associated with a significant increase in risk of overall death (relative risk [RR] = 3.50; 95% CI, 1.14 to 10.77; P =.029), risk of death owing to disease (RR = 3.98; 95% CI, 1.11 to 14.33; P =.034), and risk of disease recurrence (RR = 3.29; 95% CI, 1.18 to 9.14; P =.023). Smoking was associated with three-fold increases in risk for overall death, death owing to disease, and recurrence after adjustment for cancer-associated symptom severity and alcohol use, but the 95% CI for these adjusted risk estimates each included the null. CONCLUSION Survival differed significantly between never smokers and ever smokers with SCCHN. These results are not substantively explained by differences in cancer-associated symptoms or alcohol use, but the CIs are wide and some imprecision remains. Regardless, possible fundamental differences in SCCHN between ever smokers and never smokers may exist, and further molecular characterization of these tumors is needed to determine whether biologic differences needing targeted therapies exist.

Serum Cotinine Concentration and Wound Complications in Head and Neck Reconstruction

Background: The authors examined whether the preoperative serum concentrations of cotinine accurately predict the risk of complications in patients undergoing flap reconstruction of head and neck cancer defects. Methods: Patients with incident stage III or IV squamous cell carcinoma of the head and neck undergoing resection with pedicled or free flap reconstruction were selected from an existing database of 500 patients with squamous cell carcinoma of the head and neck who participated in a prospective epidemiologic study and were reviewed retrospectively. Preoperative serum cotinine concentrations were determined using a competitive microplate immunoassay. Complications were defined as any adverse postoperative wound outcome at either the donor or recipient site. Results: Eighty-nine patients underwent 101 flap reconstructions. Thirty-seven wound complications occurred in 33 patients. Forty of the 89 patients had a serum cotinine concentration greater than 10 ng/ml; twenty (50 percent) developed postoperative complications, whereas only 13 of 49 patients (27 percent) with a serum cotinine concentration of 10 ng/ml or less developed complications (p = 0.028). The relative risk of wound complications for those with a cotinine concentration greater than 10 ng/ml was approximately double that of patients with a lower cotinine concentration (relative risk, 1.9; 95 percent CI, 1.1 to 3.3). Patients with a cotinine concentration greater than 50 ng/ml had a particularly high risk (relative risk, 2.3; 95 percent CI, 1.1 to 16.7; p = 0.024). The relative risk of wound complications was not significantly associated with self-reported smoking status or history. Conclusion: A serum cotinine concentration greater than 10 ng/ml may predict an increased risk of wound complication in head and neck flap reconstruction and may serve as an objective, easily measured variable with which to identify patients who may benefit from an aggressive smoking cessation program before surgery.

Matched Pair Analysis of Race or Ethnicity in Outcomes of Head and Neck Cancer Patients Receiving Similar Multidisciplinary Care

It is unknown whether population-level racial or ethnic disparities in mortality from squamous cell carcinoma of the head and neck (SCCHN) also occur in the setting of standardized multidisciplinary-team directed care. Therefore, we conducted a matched-pair study that controlled for several potentially confounding prognostic variables to assess whether a difference in survival exists for African American or Hispanic American compared with non-Hispanic white American SCCHN patients receiving similar care. Matched pairs were 81 African American case and 81 non-Hispanic white control patients and 100 Hispanic American cases and 100 matched non-Hispanic white controls selected from 1,833 patients of a prospective epidemiologic study of incident SCCHN within a single, large multidisciplinary cancer center. Matching variables included age (±10 years), sex, smoking status (never versus ever), site, tumor stage (T1-2 versus T3-4), nodal status (negative versus positive), and treatment. Cases and controls were not significantly different in proportions of comorbidity score, alcohol use, subsite distribution, overall stage, or tumor grade. Matched-pair and log-rank analyses showed no significant differences between cases and controls in recurrence-free, disease-specific, or overall survival. Site-specific analyses suggested that more aggressive oropharyngeal cancers occurred more frequently in minority than in non-Hispanic white patients. We conclude that minority and non-Hispanic white SCCHN patients receiving similar multidisciplinary-team directed care at a tertiary cancer center have similar survival results overall. These results encourage reducing health disparities in SCCHN through public-health efforts to improve access to multidisciplinary oncologic care (and to preventive measures) and through individual clinician efforts to make the best multidisciplinary cancer treatment choices available for their minority patients. The subgroup finding suggests a biologically based racial/ethnic disparity among oropharyngeal patients and that prevention and treatment strategies should be tailored to different populations of these patients.

After the smoke clears: Environmental and occupational risks for carcinoma of the upper aerodigestive tract

Both environmental and occupational exposures are associated with the development of carcinomas of the upper aerodigestive tract, although most squamous cell carcinomas of the upper aerodigestive tract are related to smoking and drinking. This review discusses environmental and occupational risk factors, other than tobacco and alcohol, for carcinoma of the upper aerodigestive tract and the difficulties encountered when attempts are made to study these environmental and occupational exposures. However, this is not an all-inclusive review; rather, it is designed to give the reader an understanding of the topic, to allow for appropriate counseling of patients, and perhaps to advance public health initiatives.

Knowledge of Head and Neck Cancer Among Medical Students at 2 Chicago Universities

OBJECTIVE To assess the knowledge of first- (M1) and fourth- (M4) year medical students regarding head and neck cancer (HNC) risk factors, signs, symptoms, and frequency; designated oral screening recommendations; head and neck physical examination techniques; and medical school curriculum on this subject. DESIGN Cross-sectional cohort study using a survey questionnaire. SETTING Two metropolitan-area medical schools in Chicago, Illinois. PARTICIPANTS Of 601 M1 and M4 medical students, 304 completed the survey. MAIN OUTCOME MEASURES Percentage of medical students from 2 classes at 2 different universities who knew baseline knowledge about HNC. RESULTS The response rate was approximately 50% for each class from each university. The M1 students from the 2 institutions differed on identifying a lump in the neck and voice changes among the signs and symptoms associated with HNC and American Cancer Society examination recommendations. The M4 students did not differ between the 2 schools and were more knowledgeable than the M1 students on risk factors, signs, symptoms, most frequent histologic type, American Cancer Society recommendations, and common subsites of HNC. Curricular experiences, as expected, varied between M1 and M4 students. CONCLUSIONS This study demonstrates an increase in knowledge about HNC in M4 students compared with M1 students. Yet, graduating students are still deficient regarding certain risk factors, oral screening guidelines, head and neck examination techniques, and medical school curriculum. Further efforts should be aimed at expanding head and neck education for medical students.

Frequent and differential mutations of the CYLD gene in basal cell salivary neoplasms: linkage to tumor development and progression

Basal cell salivary neoplasms display similar cyto-morphologic features and are classified into adenoma and adenocarcinoma based on the presence or absence of tumor invasion at diagnosis. These neoplasms also share considerable phenotypic resemblance and co-exist with certain dermal adnexal tumors harboring the CYLD gene mutations inferring common genetic association. We sequenced the CYLD gene in both basal cell adenomas and adenocarcinomas and correlated the findings with CYLD, NF-κB, and β-catenin expression levels and clinicopathologic factors. Twenty mutations were identified and comprised of 3 synonymous and 17 non-synonymous (missense) types involving the coding exons of the CYLD gene. Mutations in exons 9–11 were identified in both adenomas and adenocarcinomas, while mutations in exons 12–20, encoding the USP domain, were exclusively found in carcinomas. Although no significant correlation between CYLD mutations and expression levels of CYLD, NF-κB, and β-catenin or clinicopathologic parameters was found, basal cell adenocarcinomas with multiple mutations showed reduction in CYLD protein expression and pursued aggressive clinical behavior. Our study revealed high incidence and sequential CYLD mutations in both basal cell adenoma and adenocarcinoma supporting a single neoplastic continuum for their evolution and provides evidence for potential diagnostic and therapeutic utility.

Frequent PTEN loss and differential HER2/PI3K signaling pathway alterations in salivary duct carcinoma: Implications for targeted therapy: PI3K Pathway in Salivary Duct Carcinoma

Patients with advanced primary and recurrent salivary duct carcinoma (SDC), a rare and lethal malignancy, have limited therapeutic options. Novel small‐molecule agents aimed at targeting critical signaling associated with SDC tumorigenesis may lead to new therapeutic options for patients with these tumors. The human epidermal growth factor receptor 2 (HER2)/phosphoinositide 3‐kinase (PI3K) axis, an important oncogenic pathway, has been targeted for therapy in several solid tumors. Currently, little is known about the role and clinical implications of alterations of the HER2/PI3K pathway in patients with SDC.

Mucoepidermoid carcinoma post−radioactive iodine treatment of papillary thyroid carcinoma: unique presentation and putative etiologic association

We report the development of mucoepidermoid carcinomas of the parotid gland in 2 adult patients after a relatively short duration of radioactive iodine (RAI) treatment of papillary thyroid carcinoma. Both instances, together with those previously reported, underscore the selective nature of the mucoepidermoid carcinoma phenotype development in patients with papillary thyroid carcinoma as a consequence of RAI treatment. Efforts to alleviate salivary pathophysiologic damage by RAI in these patients are warranted.