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Purpose To determine if phosphodiesterase 5 (PDE5) inhibitors can augment immune function in head and neck cancer patients through inhibition of myeloid derived suppressor cells (MDSCs). Experimental Design We performed a randomized, prospective, double blinded, placebo controlled, phase II clinical trial to determine the in vivo effects of systemic PDE5 inhibition on immune function in head and neck squamous cell carcinoma (HNSCC) patients. Results Tadalafil augmented immune response, increasing ex vivo T cell expansion to a mean 2.4 fold increase compared to 1.1 fold in control patients (P= 0.01), reducing peripheral MDSC numbers to mean 0.81 fold change compared to a 1.26 fold change in control patients (P=0.001), and increasing general immunity as measured by delayed type hypersensitivity response (P=0.002). Tumor specific immunity in response to HNSCC tumor lysate was augmented in tadalafil treated patients (P=0.04). Conclusions These findings demonstrate that tadalafil augments general and tumor-specific immunity in HNSCC patients and has therapeutic potential in HNSCC. Evasion of immune surveillance and suppression of systemic and tumor specific immunity is a significant feature of head and neck cancer development. This study demonstrates that a PDE5 inhibitor, tadalafil, can reverse tumor specific immune suppression in head and neck cancer patients, with potential for therapeutic application.

Evidence supporting prophylactic swallow exercises for patients with head and neck cancer (HNC) has not been universally demonstrated. This RCT examined diet level, feeding tube use, swallow function, and quality of life (QOL) of patients undergoing chemoradiotherapy who performed prophylactic swallowing exercises. Sixty HNC patients were randomized into exercise versus control groups. Swallowing, oromotor, toxicity, and QOL data were recorded (baseline, 3, 6, 12, 24 months). Physiological swallow function was examined at baseline and 3 months. Swallow exercises were completed twice daily. Oral intake at 3 months was 10% better in the exercise group, which was not statistically significant (p = 0.49). Significant (p < 0.05) differences in secondary outcomes including oromotor function, pharyngeal impairment, oral pharyngeal swallow efficiency, and incisal opening were noted at early time points (3–6 months) in the exercise group. Possible positive early improvements in swallow function are associated with swallowing exercises, although these improvements are not significant longer term.

IMPORTANCE Detection of persistent oral human papillomavirus (HPV) DNA may be associated with recurrence of HPV-positive head and neck squamous cell carcinoma (HNSCC).OBJECTIVE To evaluate the dynamics of oral HPV DNA detection and associations with disease outcomes in patients with HPV-positive and HPV-negative HNSCC. DESIGN, SETTING, AND PARTICIPANTSThis prospective, 2-institution, tertiary referral center study of 396 patients with newly diagnosed oral cavity or oropharyngeal HNSCC was performed from July 11, 2011, to May 7, 2016. Oral rinse samples were prospectively collected at diagnosis and at completion of primary therapy. Weekly oral rinse samples were collected during radiotherapy. Purified tumor and oral rinse sample DNA were evaluated for 37 HPV types, and viral load was quantified by type-specific real-time polymerase chain reaction. Cancers were stratified by tumor HPV status, and HPV was classified as tumor type if identical to that detected in the tumor or nontumor type. MAIN OUTCOMES AND MEASURES Prevalence of HPV DNA before, during, and after therapy. Associations between tumor-type and nontumor-type oral HPV DNA detection and recurrence-free and overall survival were evaluated. RESULTS Of the 396 patients (median age, 59 years [range, 19-96 years]; 295 [74.5%] men; and 354 [89.4%] white race/ethnicity), 217 had oropharyngeal cancer; 170, oral cavity cancer; and 9, unknown primary HNSCC. The prevalence of oral HPV detection at diagnosis was higher among patients with HPV-positive compared with HPV-negative HNSCC (24 of 194 [84.2%] vs 170 of 202 [12.4%]; P < .001). Oral HPV-16 DNA had an 81% sensitivity and 100% specificity for HPV-16-positive HNSCC. The prevalence and load of tumor-type HPV decreased significantly during primary therapy with odds ratio for probability of infection with each increasing month after diagnosis (0.41; 95% CI, 0.33-0.52; P < .001), whereas those of nontumor types did not (1.01; 95% CI, 0.97-1.06; P = .62). Current smoking was significantly associated with a reduced clearance of tumor-type HPV DNA (hazard ratio [HR], 0.54; 95% CI, 0.32-0.93). Two-year overall survival was significantly lower among the HPV-positive patients with persistent detection of tumor-type HPV after therapy than among those without detectable tumor-type DNA after therapy (68% vs 95%; adjusted HR, 6.61; 95% CI, 1.86-23.44; P = .003), as was recurrence-free survival (55% vs 88%; adjusted HR, 3.72; 95% CI, 1.71-8.09; P < .001). No associations were observed for nontumor type HPV DNA among patients with HPV-positive or HPV-negative HNSCC. CONCLUSIONS AND RELEVANCEPrevalence and viral load of tumor-type HPV DNA decreased rapidly with therapy, and persistent detection was associated with increased risk of recurrence and death. Analysis of tumor type HPV DNA has considerable promise as a biomarker for treatment response and risk of progression.

The interaction between NLR and HPV status suggests that HPV status may be a determining factor in the favorable prognosis associated with a decreased NLR in HNSCC; these findings also suggest that HPV status may interact with the prognostic associations of indicators of systemic inflammation in HNSCC. © 2017 Wiley Periodicals, Inc. Head Neck 39: 662-667, 2017.