Development and validation of a product acceptability questionnaire for intranasal Q-Griffithsin COVID-19 prophylaxis (SPRAY PAL).

OBJECTIVES: Patient experiences are critical when determining the acceptability of novel interventional pharmaceuticals. Here, we report the development and validation of a product acceptability questionnaire (SPRAY PAL) assessing feasibility, acceptability and tolerability of an intranasal Q-Griffithsin (Q-GRFT) drug product designed for COVID-19 prophylaxis. DESIGN: SPRAY PAL validation was undertaken as part of an ongoing phase 1 clinical trial designed to test the safety, pharmacokinetics and tolerability of intranasally administered Q-GRFT for the prevention of SARS-CoV-2 infection. SETTING: The phase 1 clinical trial took place at a University Outpatient Clinical Trials Unit from November 2021 to September 2023. PARTICIPANTS: The initial SPRAY PAL questionnaire was piloted among healthy volunteers ages 25 to 55 in phase 1a of the clinical trial (N=18) and revised for administration in phase 1b for participants ages 24-59 (N=22). RESULTS: Spearman correlations tested convergent and discriminant validity. Internal consistency was assessed using Cronbach's alpha, and test-retest reliability was assessed using intraclass correlation coefficients of responses collected from three repeated questionnaire administrations. The initial version demonstrated excellent internal consistency. The revised version demonstrated very good internal consistency after removal of one item (alpha=0.739). Excellent test-retest reliability (intraclass coefficient=0.927) and adequate convergent (r's=0.208-0.774) and discriminant (r's=0.123-0.392) validity were achieved. Subscales adequately distinguished between the constructs of acceptability, feasibility and tolerability. CONCLUSIONS: The SPRAY PAL product acceptability questionnaire is a valid and reliable patient-reported outcomes measure that can be considered a credible tool for assessing patient-reported information about product acceptability, feasibility of use, tolerability of product and side effects and cost of product for novel intranasal drug formulations. The SPRAY PAL is generalisable, and items may be readily adapted to assess other intranasal formulations. TRIAL REGISTRATION NUMBERS: NCT05122260 and NCT05437029.

Prognostic significance of HPV status in postoperative squamous-cell carcinoma of the head and neck.

BACKGROUND: There are limited data on the prognostic significance of human papillomavirus (HPV) status in relation to traditional risk factors for head and neck squamous-cell carcinoma (HNSCC) in the postoperative setting. OBJECTIVE: To clarify the impact of HPV status on the risk for HNSCC in the postoperative setting. METHODS: We retrospectively evaluated an institutional cohort of 128 patients with HNSCC patients who had been treated with definitive surgery with or without adjuvant radiotherapy or chemoradiotherapy. Patient, disease, and treatment factors were analyzed as potential prognostic indicators. RESULTS: Lymph node extracapsular extension (ECE), perineural invasion (PNI), and lymphovascular space invasion (LVSI) positivity predicted poorer locoregional control (LRC), disease-free survival (DFS), and overall survival (OS). Positive margins related to poorer DFS and OS. HPV status alone did not predict LRC, DFS, or OS. Compared with patients who were HPV-positive and ECE-negative, both HPV-positive and HPV-negative patients with ECE experienced significantly poorer OS (78.6%, 60%, and 43.7%, respectively; 𝑃 = .010 and 𝑃 = .018, respectively). LIMITATIONS: Retrospective, single-institution study; small patient cohort; short follow-up time. CONCLUSION: The influence of HPV in postoperative HNSCC seems limited compared with traditional risk factors such as ECE, LVSI, and PNI. De-escalation of postoperative treatment based on HPV status alone should be approached with caution.

Human papillomavirus E7 serology and association with p16 immunohistochemistry in squamous cell carcinoma of the head and neck.

BACKGROUND: Human papillomavirus (HPV)-positive oropharyngeal cancer is associated with improved survival and treatment response as compared to HPV-negative cancers. P16 overexpression is widely accepted as a surrogate marker for HPV positivity. METHODS: A total of 92 serum samples from 75 head and neck squamous cell carcinoma (HNSCC) patients were examined for HPV16 and 18 E7 antibodies by ELISA. Available tissue was tested for HPV-DNA by PCR, and p16 immunohistochemistry was obtained from a deidentified database. RESULTS: Of 75 HNSCC patients, 25 were HPV E7 seropositive. Seropositivity was strongly associated with cancers of the oropharynx, and correlated with positive p16 immunohistochemistry (IHC) and HPV-DNA. Post-treatment serum was available in a limited subset of patients, revealing a decrease in antibody titers following response to treatment. CONCLUSIONS: HPV E7 seropositivity correlated with positive tumor HPV-DNA and p16 expression, and was strongly associated with cancers of the oropharynx. E7 serology warrants further study as a potential biomarker in HPV-positive HNSCC.

Persistent tracheostomy after primary chemoradiation for advanced laryngeal or hypopharyngeal cancer.

BACKGROUND: Despite the demonstrated survival equivalence between chemoradiation and ablative surgery as primary treatment for advanced laryngeal and hypopharyngeal cancers, a subset of patients who undergo organ-preservation therapy have persistent tracheostomy requirement after completion of treatment. METHODS: Patients who received primary chemoradiation for advanced laryngeal or hypopharyngeal cancer in a 3-year interval were identified. Rate of persistent posttreatment tracheostomy requirement was evaluated. The 12-month overall mortality rate was compared between patients who did and did not receive a tracheostomy before treatment. RESULTS: In 60 patients identified for this study, T3/T4 status and hemilarynx fixation at the time of presentation were associated with persistent tracheostomy requirement 6 and 12 months posttreatment (p = .022; p < .001; and p = .032; p = .0495, respectively). Twelve-month mortality was higher in T3/T4 patients who received pretreatment tracheostomy (p = .034). CONCLUSION: Patients with advanced laryngeal or hypopharyngeal cancer who require tracheostomy before treatment have low rates of decannulation and higher short-term mortality than those who do not require tracheostomy before organ-preservation therapy.

Sentinel lymph node status is the most important prognostic factor in patients with melanoma of the scalp.

OBJECTIVES/HYPOTHESIS: To compare clinicopathologic and prognostic factors associated with scalp melanomas and nonscalp melanomas of the head and neck (H&N). STUDY DESIGN: Post hoc analysis of the database from a multi-institutional, prospective, randomized study. METHODS: Clinicopathologic factors were assessed and correlated with survival and recurrence. Univariate and multivariate analysis of prognostic factors affecting disease-free survival and overall survival were performed. RESULTS: Of 405 patients with H&N melanomas ≥1.0 mm Breslow thickness, 109 patients had melanoma of the scalp. All were Caucasian (100%), with most being male (79.5%) with a mean age of 49.8 years. The mean Breslow thickness was 2.4 mm; 25% had signs of ulceration. Sentinel lymph node (SLN) positivity was seen in 20.9% of scalp melanoma patients, and was more likely in younger patients (44.7 vs. 50.8 years, P = .04) and in those with a Breslow thickness of 2 to 4 mm (P = .005). The incidence of locoregional and distant recurrence were similar. Overall survival for scalp melanoma patients was significantly impacted by SLN positivity (P = .03), whereas Breslow thickness and ulceration status predicted poorer survival in nonscalp melanoma patients (P = .005, P < .0001, respectively). CONCLUSIONS: In the Sunbelt Melanoma Trial, SLN status was the strongest predictor of overall survival in scalp melanoma. Tumor thickness and ulceration correlated with poorer overall survival in nonscalp H&N melanoma. The prognostic significance of SLN status in the H&N may vary with the melanoma site.

Treatment outcome in the residually positive neck after definitive chemotherapy and irradiation.

OBJECTIVE: Determine prevalence of viable malignancy in patients undergoing neck dissection (ND) for residual neck disease following concomitant chemotherapy and irradiation (chemo/xrt) for upper aerodigestive squamous carcinoma. To determine survival in groups with a neck complete response to those who had residual disease requiring neck dissection. STUDY DESIGN: Retrospective chart review. METHODS: Retrospective chart review of 230 patients who underwent definitive chemo/xrt for primary squamous cell carcinoma cancer (SCCa) of the head and neck from 2005 to 2009 in one institution. RESULTS: Thirty-nine (17%) patients underwent ND for residual neck mass within 4 months posttreatment. Forty-nine percent (19/39) were pathologically positive for malignancy and 51% (20/39) were negative. The probability of a +ND based on original N-stage was not statistically significant (P = .368). Primary site did not yield significant probability of having +ND, except in the oral cavity (P = .02). Patients had similar overall 5-year survival, among those with a delayed complete response in the neck (66%), ND for residual disease (71%), or those with initial complete response (71%). Lower initial N-stage demonstrated improved survival in all outcome groups. Tonsil SCCa patients who underwent ND had improved survival compared to those with delayed complete response (87.5 vs. 75.8%), both of which had increased survival compared to initial complete responders (65%). CONCLUSIONS: This study supports the use of ND in the postchemo/xrt positive neck regardless of primary site or initial N-stage. ND in this setting conveys survival equal to patients with complete response in the neck after chemo/xrt. These survivorship implications of postchemo/xrt neck dissection extend to all sites, including tonsils.

A parallel group analysis of tonsillectomy using the harmonic scalpel vs electrocautery.

OBJECTIVE: To evaluate efficiency and postoperative morbidity in tonsillectomy using the harmonic scalpel (HS) vs conventional electrocautery (EC). DESIGN: A retrospective medical chart review of all patients who underwent tonsillectomy at a single children's hospital during a 32-month period from January 2001 to August 2003. PATIENTS: The charts of 605 patients who underwent tonsillectomy or adenotonsillectomy were reviewed. The patients were stratified into 2 groups based on the dissecting instrument used (HS vs EC). Each group consisted of 2 subcategories based on age (< or =7 years and >7 years). Data collected included age, sex, operative indication, operative time, postanesthetic recovery room time, pain scale scores, postoperative admissions, and postoperative morbidities. RESULTS: There were significant differences in mean age (P<.001), mean weight (P<.001), and indication for surgery (P<.001) between the 2 methods: HS patients were younger, weighed less, and more often had obstructive symptoms as their primary operative indication compared with the EC group. Average operative times were not significantly different between methods. No differences were noted with respect to recovery time (HS group, P = .10; EC group, P = .30), postoperative oxygen requirements (HS group, P = .07; EC group, P = .09), and postoperative pain scores (HS group, P = .31; EC group, P = .58). There was a significant difference in postoperative admissions between the 2 methods in patients 7 years or younger (P = .005). Finally, we noted a significant difference in postoperative bleeding between the HS (2/292) and EC (13/313) methods when the data were compared per age group (P = .006), but the overall bleeding rate was not statistically significant owing to the small number of total bleeding instances (15/605). CONCLUSIONS: Recent prospective studies indicate that the HS provides advantages over conventional EC with respect to postoperative pain and return to normal activity. This study shows that HS tonsillectomy was as efficient as the conventional EC method. In addition, there was evidence that the rate of postoperative bleeding was significantly reduced by using the HS vs conventional EC.