Programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors have provided clinical benefit to head and neck squamous cell carcinoma (HNSCC) patients in recent clinical trials. However, it ...remains unclear as to whether human papillomavirus (HPV) status is associated with improved clinical outcome of anti-PD-1 or anti-PD-L1 immunotherapy in HNSCC.
PubMed, EMBASE, Cochrane Library, and Web of Science were systematically searched up to February 28, 2021. Published clinical trials of HNSCC patients treated with only PD-1 or PD-L1 inhibitors were selected. The primary or secondary outcome of these studies included objective response rate (ORR) stratified by HPV status. The pooled odds ratio (OR) and hazard ratio (HR) were estimated using a fixed-effect model.
A total of seven eligible studies comprising 814 patients were included. The ORR of HPV positive HNSCC patients was significantly higher than that of HPV negative HNSCC patients (OR = 1.77; 95%CI = 1.14-2.74;
= 0.01), and this favorable effect occurred in pooled anti-PD-L1 trials (OR = 2.66; 95%CI = 1.16-6.11;
= 0.02). In comparison, the pooled OR was 1.51 in anti-PD-1 trials (95%CI = 0.90-2.54;
= 0.12). Survival analysis indicated that HPV positive HNSCC patients had a lower risk of overall death as compared to HPV negative HNSCC patients (HR = 0.77; 95%CI = 0.60-0.99;
= 0.04).
HPV positive HNSCC patients display improved outcomes with PD-1/PD-L1 axis blockade as compared to HPV negative HNSCC patients. These improved outcomes are likely driven to a greater extent by anti-PD-L1 inhibitors. However, randomized controlled trials with greater numbers of patients are needed for validation of these early findings.
Introduction:
The objective of this study was to compare complications and other perioperative outcomes between intraoral and transcervical drainage of both retropharyngeal and parapharyngeal ...abscesses.
Materials and Methods:
This was a retrospective study that analyzed data from the 2012 to 2016 National Surgical Quality Improvement Program (NSQIP)-Pediatric public use files. Baseline characteristics and perioperative outcomes including postoperative complications and length of hospital stay (LOS) were compared between intraoral and transcervical drainage groups. Multivariable logistic regression was performed to inspect predictors of having an extended LOS, defined as LOS greater than 3 days.
Results:
A total of 1174 patients were included. Mean age was 5.1 ± 3.8 years in the intraoral group (N = 1063) and 4.2 ± 4.3 years in the transcervical group (N = 111, P < .001). There was no significant difference in the rate of post-operative complications between groups (5.7% intraoral vs 8.1% transcervical, P = .316). LOS was significantly longer in the transcervical group (>3 days in 36.2% of intraoral vs 49.5% of transcervical, P = .006). Patients in the transcervical group had 1.59 times the odds of extended LOS, after adjusting for age, pre-operative ventilator support, asthma, structural pulmonary disease, hematologic disorders, and all post-operative complications (P = .024).
Conclusion:
There does not appear to be a significant difference in the rate of post-operative complications after intraoral versus transcervical drainage for pharyngeal abscesses in children. However, transcervical drainage was associated with an extended hospital stay. Further prospective studies will be needed to determine the reasons for this.
Given the recent successes of anti‐PD‐1 immunotherapy, many clinical trials have sought to assess the safety and efficacy of this treatment modality in the neoadjuvant setting. This systematic review ...provides a comprehensive summary of findings from neoadjuvant head and neck cancer immunotherapy clinical trials with a focus on PD‐1/PD‐L1 axis blockade. Pubmed, Embase, Cochrane Library, Web of Science, Google Scholar, and clinicaltrials.gov were systematically searched for all eligible neoadjuvant head and neck cancer immunotherapy clinical trials. Eight clinical trials met the inclusion criteria comprising a total of 260 patients. Study drugs included nivolumab, pembrolizumab, ipilimumab, durvalumab, and tremelimumab. The overall mean objective response rate (ORR) was 45.9 ± 5.7% with a 41.5 ± 5.6% single agent mean ORR. There were no deaths due to immune‐related toxicities. Neoadjuvant immunotherapy for mucosal head and neck squamous cell cancer has demonstrated favorable response rates with no unexpected immune‐related toxicities in phase I/II clinical trials.
This study examines the association between patient-reported allergy history and immune checkpoint inhibition (ICI) response in patients with recurrent or metastatic head and neck squamous cell ...carcinoma (RMHNSCC).
Retrospective cohort study.
Academic tertiary care hospital.
Data were collected from the electronic medical records on baseline age, sex, allergy history, human papillomavirus status, T-stage, N-stage, smoking status, and survival for patients with and without an allergy history. The primary outcome was ICI response defined as complete or partial response by the RECIST criteria. Chi-square and logistic regression analyses were conducted to compare rates and odds of ICI response. Kaplan-Meier analyses were used to compare survival between groups.
Our study included 52 patients with an allergy history and 36 patients without an allergy history. The groups were similar in age, sex, HPV status, smoking status, and T- and N-stage. Patients with an allergy history (17/52, 32.1%) had a greater ICI response rate than patients without allergy history (4/36, 11.1%) (P = .02). After adjusting for HPV, patients with allergies had 3.93 (1.19-13.00) times increased odds of ICI response compared to patients without allergies. The median progression-free survival was 6.0 and 4.2 months for patients with and without an allergy history respectively (log-rank, P = .04). The median overall survival was 25.0 and 11.1 months for patients with and without an allergy history respectively (log-rank, P = .002).
Patient-reported allergy history was associated with ICI response in patients with RMHNSCC, underscoring the potential clinical utility of allergy history in estimating ICI response.
Abstract
Objectives
To explore the impact of pre‐existing comorbidities on immunotherapy response, overall and progression‐free survival, and immune‐related adverse events (irAEs) of patients with ...advanced head and neck cancer (HNC) treated with immunotherapy.
Patients and methods
Ninety‐three patients treated with immunotherapy were identified and stratified into comorbidity absent or present (CCI < 1 and CCI ≥ 1, respectively) cohorts, and clinical outcomes were compared between these two groups.
Results
Patients with no comorbidities had longer overall survival (aHR = 2.74, 95% CI 1.18, 6.40,
p
= 0.02) and progression‐free survival (aHR = 2.07, 95% CI 1.03, 4.16,
p
= 0.04) and a higher tumor response rate (32% in CCI < 1 vs. 14% in CC ≥ 1,
p
= 0.05). Risk for irAEs was higher in the comorbidity absent group (
p
= 0.05).
Conclusion
Comorbidity should be considered as a significant prognostic factor in clinical decision‐making for patients with advanced HNC undergoing immunotherapy.
Objectives/Hypothesis
To investigate differences in the immunogenomic landscape among young patients presenting with oral cavity squamous cell carcinoma (OCSCC).
Study Design
Retrospective database ...review.
Methods
Normalized messenger mRNA expression data were downloaded from The Cancer Genome Atlas (TCGA) database. OCSCC patients were categorized into young and older age groups with a cutoff of 45 years. Human papillomavirus–positive tumors were excluded. Cell fractions, marker expression, and mutational load were compared between age groups using the Wilcoxon rank sum test. Adjustment for multiple comparisons was performed using the Benjamini‐Hochberg method, with a false discovery rate of 0.05.
Results
Two hundred forty‐five OCSCC tumors were included; 21 (8.6%) were young (37.1 ± 7.5 years) and 224 (91.4%) were older (64.5 ± 10.3 years). There was no significant difference between groups in the fraction of B and T lymphocytes, macrophages, monocytes, natural killers, and dendritic cells. Cytolytic activity score was decreased in young patients (8.33 vs. 18.9, P = .023). Additionally, young patients had significantly lower expression of immunomodulatory markers of immune activation, including PD‐1 (PDCD1, P = .003), CTLA4 (P = .025), TIGIT (P = .002), GITR (TNFRSF18, P = .005), OX40 (TNFRSF4, P = .009), LAG‐3 (P < .001), and TIM‐3 (HAVCR2, P = .002). Young patients had a significantly lower number of single nucleotide variant‐derived neoantigens (26.2 vs. 60.6, P < .001).
Conclusions
OCSCC patients aged 45 years and younger appear to have an attenuated immune response that may be related to a lower frequency of immunogenic mutations. This may contribute to the pathogenesis of these tumors, and ultimately help inform personalized immune‐based therapeutic strategies for young patients with OCSCC.
Level of Evidence
NA Laryngoscope, 131:304–311, 2021
Human papillomavirus (HPV)-positive status in patients with oropharyngeal squamous cell carcinoma (OPSCC) is associated with improved survival compared with HPV-negative status. However, it remains ...controversial whether HPV is associated with improved survival among patients with nonoropharyngeal and cervical squamous cell tumors.
To investigate differences in the immunogenomic landscapes of HPV-associated tumors across anatomical sites (the head and neck and the cervix) and their association with survival.
This cohort study used genomic and transcriptomic data from the Cancer Genome Atlas (TCGA) for 79 patients with OPSCC, 435 with nonoropharyngeal head and neck squamous cell carcinoma (non-OP HNSCC), and 254 with cervical squamous cell carcinoma and/or endocervical adenocarcinoma (CESC) along with matched clinical data from TCGA. The data were analyzed from November 2020 to March 2021.
Positivity for HPV was classified by RNA-sequencing reads aligned with the HPV reference genome. Gene expression profiles, immune cell phenotypes, cytolytic activity scores, and overall survival were compared by HPV tumor status across multiple anatomical sites.
The study comprised 768 patients, including 514 (66.9%) with HNSCC (380 male 73.9%; mean SD age, 59.5 10.8 years) and 254 (33.1%) with CESC (mean SD age, 48.7 14.1 years). Human papillomavirus positivity was associated with a statistically significant improvement in overall survival for patients with OPSCC (adjusted hazard ratio aHR, 0.06; 95% CI, 0.02-0.17; P < .001) but not for those with non-OP HNSCC (aHR, 0.64; 95% CI, 0.31-1.27; P = .20) or CESC (aHR, 0.50; 95% CI, 0.15-1.67; P = .30). The HPV-positive OPSCCs had increased tumor immune infiltration and immunomodulatory receptor expression compared with HPV-negative OPSCCs. Compared with HPV-positive non-OP HNSCCs, HPV-positive OPSCCs showed greater expression of immune-related metrics including B cells, T cells, CD8+ T cells, T-cell receptor diversity, B-cell receptor diversity, and cytolytic activity scores, independent of tumor variant burden. The immune-related metrics were similar when comparing HPV-positive non-OP HNSCCs and HPV-positive CESCs with their HPV-negative counterparts. The 2-year overall survival rate was significantly higher for patients with HPV-positive OPSCC compared with patients with HPV-negative OPSCC (92.0% 95% CI, 84.8%-99.9% vs 45.8% 95% CI, 28.3%-74.1%; HR, 0.10 95% CI, 0.03-0.30; P = .009).
In this cohort study, tumor site was associated with the immune landscape and survival among patients with HPV-related tumors despite presumed similar biologic characteristics. These tumor site-related findings provide insight on possible outcomes of HPV positivity for tumors in oropharyngeal and nonoropharyngeal sites and a rationale for the stratification of HPV-associated tumors by site and the subsequent development of strategies targeting immune exclusion in HPV-positive nonoropharyngeal cancer.
Tumor histological factors that predict immunotherapy response in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) are not well defined.
To investigate the ...association between tumor grade and immunotherapy response in patients with recurrent or metastatic mucosal HNSCC.
In this retrospective cohort study, the medical records of 60 patients with recurrent or metastatic mucosal HNSCC treated with immune checkpoint inhibitors at Johns Hopkins Hospital between July 1, 2015, and January 22, 2020, were reviewed.
High-grade tumors (HGTs) vs low-grade tumors (LGTs) in recurrent or metastatic HNSCC.
Patients were divided into 2 groups: those with LGTs (well differentiated and moderately differentiated) and those with HGTs (poorly differentiated). The main outcome was a clinically beneficial immunotherapy response, defined as complete response or partial response. Univariable and multivariable logistic regressions were conducted to calculate odds ratios for each variable's association with immunotherapy response. Survival differences were evaluated using Kaplan-Meier survival curves with multivariable Cox proportional hazards regression models.
The 60 patients (35 with HGTs and 25 with LGTs) had a mean (SD) age of 64.6 (8.88) years; 51 were male (85%); and 38 were current or former smokers (63%). The oropharynx was the most common primary tumor site both in patients with HGTs (22 of 35; 63%) and those with LGTs (12 of 25; 48%). Bivariate analysis showed the proportion of patients having a beneficial response to immunotherapy was greater for patients with HGTs (12 of 35; 34.3%) than those with LGTs (2 of 25, 8.0%) (difference, 26.3%; 95% CI, 7.3%-45.3%). Upon multivariable analysis, patients with HGTs had 5.35-fold increased odds (95% CI, 1.04-27.37) of having a clinically beneficial response to immunotherapy. Among patients with available tumor genomic profiling data, the mean tumor mutational burden was greater for patients with HGTs (mean SD, 8.6 5.4 mut/Mb; n = 8) than patients with LGTs (mean SD, 3.6 1.1 mut/Mb; n = 4) (difference = 5.0 mut/Mb; 95% CI -1.4 to 11.4 mut/Mb; Cohen d = 1.2).
In this cohort study, tumor grade was independently associated with immunotherapy response in patients with recurrent or metastatic mucosal HNSCC. These findings highlight the potential role of tumor grade in predicting immunotherapy response in mucosal HNSCC.
•The prognostic impact of pathologic lymph nodes differs by receipt of radiotherapy.•HPV positive patients have improved survival with a positive LN compared to none.•This is particularly true in ...patients receiving post-operative radiotherapy.•LN involvement may improve anti-tumor immune responses following radiotherapy.•Otherwise, it may result in detection and treatment at earlier stages of disease.
Recent pathologic staging of HPV-positive oropharyngeal squamous cell carcinomas (OPSCC) is solely dependent on number of pathologic nodes. Using a large dataset, we aimed to understand how increase in pathologic lymph nodes (LN) associated with overall survival.
National Cancer Database was queried for HPV-positive OPSCC patients undergoing primary surgery with LN dissection between 2010 and 2013. Kaplan-Meier, univariate and multivariate Cox models were used to evaluate overall survival. Interaction between nodal status and radiotherapy was examined.
Implications of pathologic LN on overall survival differed according to receipt of post-operative radiotherapy (p-valueinteraction = 0.008). In patients who did not receive adjuvant radiotherapy, there were no significant differences in risk of death from 0 to 2 pathologic nodes (adjusted HR (aHR) 0.92, 95%CI 0.61–1.4). However, risk increased by 18% on average with each additional LN thereafter (aHR 1.18, 95%CI 1.1–1.27). Among radiotherapy patients, after adjusting for other variables, patients with 1 pathologic LN had 70% lower risk of death than those with 0 pathologic LN (aHR 0.30, 95%CI 0.14–0.64). Thereafter, risk increased on average by 7% with each additional LN (aHR 1.07, 95%CI 1–1.14).
The prognostic impact of pathologic nodes in resected HPV-positive OPSCC differs by receipt of radiotherapy, with better outcomes in post-operative radiotherapy treated patients with one pathologic LN than none. These findings suggest that LN involvement may improve anti-tumor immune responses following radiotherapy, or result in earlier detection and treatment of disease. These results merit further studies to corroborate these findings and establish the underlying mechanism.
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