Citations

Abstract Objective To describe the presenting symptoms, treatment regimens, and outcomes associated with oropharyngeal adenoid cystic carcinoma. Data Sources Ovid MEDLINE(R), Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, and Scopus via Elsevier. Review Methods This review followed the Preferred Reporting Items for Systematic Reviews and Meta‐analyses. A medical librarian conducted the literature search using controlled vocabulary and keywords, with investigator input. Eligible articles were clinical trials and observational studies reporting on clinical features, treatment, or outcomes for oropharyngeal adenoid cystic carcinoma. Results Our search identified 233 unique citations, with 44 articles included covering 195 patients. The female‐to‐male ratio was 1.7:1, and the base of the tongue was the most common subsite (73%). Presenting symptoms were mainly pain/discomfort (n = 31), followed by a palpable mass (n = 19) and dysphagia (n = 12). At diagnosis, 22.3% (29 patients) had positive lymph nodes. Treatment was primarily surgical (n = 102), with definitive radiation therapy used in 58 cases. Disease progression was noted in 86 patients, 36% (n = 31) of whom developed distant metastases—primarily to the lungs (n = 26). Long‐term outcomes (n = 76) showed 3‐ and 5‐year overall survival rates of 71.5% to 100% and 47.6% to 79.0%, and disease‐free survival rates of 54.7% to 70.0% and 21.9% to 44.0%, respectively. Conclusion Among patients with available data, oropharyngeal adenoid cystic carcinoma appeared more common in women and has a predilection for the base of the tongue. However, this finding should be interpreted with caution, given the high proportion of missing data. These tumors appear to carry a higher risk for nodal metastases and may lead to poor outcomes.

Objective(s): To (1) report on the long-term recurrence rate of surgically managed pleomorphic adenoma (PA) and (2) assess long-term surgical outcomes after parotidectomy Methods: Cross-sectional survey of all patients with a pathologic diagnosis of PA who underwent surgical management in a tertiary care center from 01/1997 to 12/2023 and had access to an electronic patient portal. Surveys were delivered via electronic patient portal or phone call with 6 questions to assess recurrence and long-term surgical outcomes. Time to first recurrence and recurrence free survival were analyzed using a Kaplan-Meier curve. Results: Seven hundred-forty-five patients met inclusion criteria and received the survey, with a 56% response rate (n = 420). The clinical median follow-up length was 51 days, which extended to a median length of 6.2 years following the survey. The median change in follow-up length was 5.37 years ( P < .001). The recurrence rate was 1% at 5 years, with a median time to first recurrence of 7.54 years. 13% and 9% of responders reported facial asymmetry and incisional cosmetic concerns, respectively. 33% of patients reported experiencing Frey syndrome, which increased from 5.2% of survey responders with documented Frey syndrome at their original post-operative assessment. Conclusion: Long-term assessment of PA outcomes confirms low recurrence rates, suggesting regular surveillance of recurrence is likely unnecessary. Complaints of Frey syndrome increased in frequency with longer term follow-up, which should be considered during patient counseling. Level of Evidence: 3

Importance Standard adjuvant therapy for human papillomavirus–associated oropharyngeal squamous cell carcinoma (HPV-OPSCC) is radiation therapy 60 Gy with or without cisplatin delivered in 30 fractions during 6 weeks. A phase 3 randomized clinical trial demonstrated decreased toxic effects and improved patient-reported outcomes with de-escalated adjuvant radiation therapy (DART) compared with standard therapy; however, outcomes for patients treated in the clinical practice setting following trial adoption remain unknown. Objective To compare characteristics and oncologic outcomes of patients treated with DART during clinical trials (on study) and in clinical practice settings (off study) and report progression-free survival (PFS) by risk category. Design, Setting, and Participants This retrospective cohort study included patients treated with DART in the MC1273 and MC1675 trials and in clinical practice after study completion at a multisite tertiary care center. Patients with surgically resectable HPV-OPSCC who underwent margin-negative resection between August 20, 2013, and March 21, 2023, and were treated with DART were included in the analysis. Those with prior head and neck cancer, pT0 or pT4 disease, unknown HPV status, metastatic disease at presentation, synchronous primary tumors, induction chemotherapy, or treatment at an outside institution were excluded. Data were analyzed from July 1, 2024, to July 18, 2025. Interventions DART consisting of 30 to 36 Gy in 1.5- to 1.8-Gy fractions twice daily with docetaxel 15 mg/m 2 on days 1 and 8. Main Outcomes and Measures Progression-free survival as measured via Kaplan-Meier analysis. Results A total of 282 patients were included in the analysis: 176 (62.4%) in the on-study group and 106 (37.6%) in the off-study group (252 [89.4%] male; mean [SD] age, 59.1 [9.3] years). Both groups were predominantly male (157 [89.2%] and 95 [89.6%], respectively) and consisted mostly of never smokers (118 [67.0%] and 62 [58.5%], respectively). Pathologic features were similar between groups except for nodal stage (pN1: 155 [88.1%] on study vs 102 [96.2%] off study; pN2: 21 [11.9%] on study vs 4 [3.8%] off study; P = .02). The median follow-up times were 5.2 years (95% CI, 5.2-5.8 years) in the on-study group and 2.2 years (95% CI, 1.9-2.4 years) in the off-study group. Two-year PFS was similar (93% [95% CI, 88%-97%] on study vs 93% [95% CI, 88%-99%] off study). For patients with pN1 and no extranodal extension (ENE), 2- and 5-year PFS were 97% (95% CI, 93%-100%) and 96% (95% CI, 92%-100%), respectively. Patients with pN1 and ENE had a 2- and 5-year PFS of 93% (95% CI, 89%-98%) and 87% (95% CI, 81%-94%), respectively. Conclusions and Relevance In this retrospective cohort study of patients receiving DART on and off study, oncologic outcomes were similar between the 2 groups. Fewer patients with pN2 received DART off study, given the interim results of MC1675. Patients with pN1 and no ENE treated with DART had excellent 2- and 5-year PFS, supporting DART as a compelling treatment option in well-selected patients. An additional study that is currently underway will evaluate biomarker risk-stratified treatment of patients with pN1 and ENE receiving DART.

IMPORTANCE Neoadjuvant chemoimmunotherapy has high rates of pathologic response and improved prognosis among solid tumors. Its role in head and neck squamous cell carcinoma (HNSCC) remains understudied. OBJECTIVE To summarize the efficacy associated with neoadjuvant chemoimmunotherapy regimens in HNSCC and to compare the efficacy associated with neoadjuvant chemoimmunotherapy vs immunotherapy alone in locoregionally advanced resectable HNSCC prior to definitive surgery. DATA SOURCES A librarian-led systematic review was conducted using multiple electronic databases, including Medline, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus, following Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) guidelines. Databases were queried from inception to October 2024. STUDY SELECTION Inclusion criteria included prospective interventional trials that have completed accrual, with results published in English. Only trials of resectable, treatment-naive HNSCC were included. Exclusion criteria included lack of reporting on pathologic response or Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 response. DATA EXTRACTION AND SYNTHESIS Two investigators independently conducted title, abstract, and full-text reviews per PRISMA guidelines. Primary outcomes extracted were major pathologic response (MPR) and complete pathologic response (CPR) at surgery and complete response (CR) on imaging by RECIST 1.1. Secondary outcomes included 1-year overall survival (OS) and toxic effects. MAIN OUTCOMES AND MEASURES A meta-analysis was performed using a binary random-effects model to determine the pooled proportion of primary outcomes in the immunotherapy and chemoimmunotherapy groups. Heterogeneity was reported as I 2 . RESULTS A total of 751 patients (502 [77%] male; age range, 27-87 years) across 23 studies were included in the meta-analysis, including 357 patients (47%) who underwent chemoimmunotherapy, 102 patients (14%) who underwent dual-agent immunotherapy, and 292 patients (39%) who underwent single-agent immunotherapy. Pooled rates of MPR plus CPR were 66% (95% CI, 58%-73%; I 2 = 0.59) for chemoimmunotherapy, 18% (95% CI, 6%-29%; I 2 = 0.65) for dual-agent immunotherapy, and 6% (95% CI, 3%-9%; I 2 &amp;lt; 0.01) for single-agent immunotherapy. Across all groups, 1-year OS rates ranged from 88% to 96% for single-agent immunotherapy, 88% to 96% for dual-agent immunotherapy, and 88% to 100% for chemoimmunotherapy. Grade 3 to 5 adverse events were reported in 61 of 210 patients (29%), 2 of 67 patients (3.0%), and 36 of 210 patients (17%) among the reporting studies in the single-agent immunotherapy, dual-agent immunotherapy, and chemoimmunotherapy groups, respectively. CONCLUSIONS AND RELEVANCE These findings suggest that neoadjuvant chemoimmunotherapy regimens were associated with higher pathologic and radiographic response rates compared with immunotherapy alone in locoregionally advanced HNSCC. These results call for phase 3 trials comparing these neoadjuvant regimens head to head.

Background: To compare oncologic and postoperative outcomes in patients with scalp squamous cell carcinoma with periosteal, but not gross calvarial, involvement, treated with margin-clearing excision including either calvarial burring or periosteal excision alone. Study Design: Retrospective cohort study. Setting: Single tertiary academic referral center. Methods: We retrospectively reviewed surgical cases from January 2001 to January 2025. Inclusion criteria: patients ≥18 years with biopsy-proven scalp squamous cell carcinoma involving the periosteum without cortical invasion on imaging. Management of the deep margin included either burring of the outer table or periosteal excision alone. Demographic, surgical, and oncologic outcomes were collected and analyzed descriptively. Results: Twenty patients met inclusion criteria. Median age was 70 (range 56-92), and 18 (86%) were male. Thirteen (65%) patients underwent calvarial burring, 7 (35%) underwent periosteal excision. Local recurrence occurred in 31% and 29% of the burring group and non-burring group. Disease-free survival at 2 years was 46% and 57% in the burring and non-burring group, respectively. Overall survival at 2 years was 77% and 86% in the burring and non-burring group. Three patients in the burring group had local recurrences with intracranial extension, 1 died of disease, 1 died with disease and concurrent meningitis, 1 is alive with disease recurrence currently on palliative treatment. There were 7 disease-related deaths. Conclusion: Burring did not confer a significant oncologic advantage compared to periosteal excision alone when there was no gross cortical invasion. Local recurrence in patients undergoing calvarial burring was associated with intracranial extension of disease.

Importance Adverse events in otolaryngology–head and neck surgery (OHNS) are inconsistently reported. The Clavien-Dindo Classification has been modified and validated in several surgical subspecialties but has yet to be validated in OHNS. Objective To create and validate a modified Clavien-Dindo Classification for OHNS that reflects the severity and duration of harm for complications experienced by patients undergoing OHNS. Design, Setting, and Participants This is a multicenter survey study of subject matter experts (SMEs) from OHNS subspecialties from academic institutions within the US. A literature review identified publications reporting surgical complications in OHNS in the English language between January 2019 and April 2020. Complications were summarized and used to inform a modified Clavien-Dindo Classification. Feedback from internal SMEs was incorporated. Thirty-five clinical vignettes were created, and an electronic survey was sent to SMEs at outside institutions. Each SME was randomly assigned to 1 of 4 groups to evaluate 8 to 9 vignettes. The survey was conducted in September 2023, and data were analyzed from February to May 2024. Exposure Participation in the electronic survey. Main Outcomes and Measures Vignette scores were assessed and the Comprehensive Complication Index (CCI) calculator was used to assess cumulative morbidity. The scale is based on the grading by the Clavien-Dindo Classification and reflects overall morbidity on a scale from 0 (no complication) to 100 (death). Variability of the CCIs between reviewers, the primary outcome, was summarized with the SD. The percentage of reviewers with a high (≥26.2) or low (&amp;lt;26.2) CCI within a vignette was reported. Reliability was summarized using Krippendorff α. Results Of 106 SMEs, 43 (response rate, 40.6%) completed at least 1 vignette. Eighteen of 35 vignettes (51.4%; 95% CI, 34.9%-68.0%) had unanimous high CCI, and 8 of 35 vignettes (22.9%; 95% CI, 8.9%-36.8%) had unanimous low CCI (overall categorical agreement, 74.3%; 95% CI, 59.8%-88.8%). On average, the Krippendorff α was 0.74, indicating moderate reliability. A total of 21 850 OHNS complications were reviewed and categorized as surgical or medical with 12 including subcategorization for specificity. Each category was then assigned a modified OHNS Clavien Dindo classification grade. Conclusions and Relevance In this survey study of OHNS experts, a modified OHNS Clavien-Dindo Classification was developed and validated using case vignettes. The modified Clavien-Dindo Classification provided a granular subcategorization for each complication category and grade, duration of harm, and an overall summary complication score (CCI). Results suggest the modified OHNS Clavien-Dindo Classification reliably differentiated between high-grade and low-grade OHNS complications and could be utilized for assessing surgical outcomes.

ABSTRACT Background ASP‐1929 photoimmunotherapy—cetuximab conjugated to IRDye 700DX and red light (690 nm) for localized drug activation—results in rapid, selective cell killing. Methods This phase Ib/II open‐label study evaluated ASP‐1929 photoimmunotherapy plus pembrolizumab in patients with recurrent/metastatic HNSCC (≥ 1 accessible lesion, PD‐L1 combined positive score ≥ 1, ineligible for standard locoregional therapy). Primary objectives were safety/tolerability and objective response rate (ORR). Secondary objectives included overall survival (OS) and progression‐free survival (PFS). Results Eighteen patients (median age 63 years, 74% male) comprised the photoimmunotherapy‐evaluable population. The confirmed ORR was 27.8% (95% CI 9.7–53.5); four of five responders had complete responses (95% CI, 6.4–47.6). Median OS was 25.6 months (95% CI, 14.6–not evaluable); median PFS was 2.9 months (95% CI, 1.4–14.6). The most common serious adverse reactions were dysphagia and tongue edema (each n = 2; 10.5%). Conclusions ASP‐1929 photoimmunotherapy plus pembrolizumab was generally tolerable, with promising efficacy in patients with recurrent/metastatic HNSCC.

ABSTRACT Human papillomavirus (HPV) is comprised of >200 genotypes and has an ~8 kb, circular, double-stranded DNA genome. Transmission of HPV occurs through skin-to-skin contact and infection of squamous epithelial cells of cutaneous and mucosal surfaces. HPV genotypes are categorized as low- or high-risk (hrHPV) based on oncogenic potential. There are approximately 14 types of hrHPV that can cause several types of cancer, including HPV-associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC). Detection of HPV(+)OPSCC is traditionally accomplished using p16 immunohistochemistry (IHC) and HPV-specific testing, either DNA or RNA in situ hybridization (ISH) staining or DNA-based PCR of suspected tumor biopsy tissue. More recently, platelet-poor plasma (PPP) samples from patients with HPV(+)OPSCC have proven useful for detection and quantitation of fragments of HPV circulating tumor DNA (ctDNA). ctDNA has been shown to be useful in determining treatment response and monitoring for disease recurrence. In this study, a novel droplet digital PCR assay (ddPCR) was developed and validated for the detection and quantitation of ctDNA from 5 hrHPV genotypes in PPP. Analytical sensitivity ranged from 7.71 to 19.45 fragments of HPV ctDNA per milliliter of PPP across five hrHPV genotypes. In patients with confirmed primary or recurrent HPV(+)OPSCC or HPV(-)OPSCC, testing of corresponding PPP samples ( n = 32) by ddPCR demonstrated 90.63% (29/32) overall agreement with p16/HPV-ISH biopsy results. Compared with reference ddPCR assays performed at outside laboratories, our ddPCR assay yielded 90% (9/10) overall agreement. This assay may provide clinicians with a tool for monitoring HPV ctDNA prior to, during, and after treatment of an HPV-associated cancer. IMPORTANCE At least 14 genotypes of human papillomavirus (HPV) have been identified to have high oncogenic potential. While molecular diagnostic testing for HPV is widely available for liquid cytologic cervical samples, testing is limited for other sample types, including liquid biopsy samples, such as platelet-poor plasma (PPP). With the rising incidence of HPV-associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC), laboratory testing is an essential part of patient diagnosis, management, and surveillance. Here, we summarize the development and analytical performance validation of a multiplexed, droplet digital PCR (ddPCR) assay for the detection and quantitation of HPV circulating tumor DNA (ctDNA) in PPP. This assay may provide clinicians with a tool to address minimal residual disease for patients with an HPV-associated cancer.