Oropharyngeal cancer outcomes correlate with p16 status, multinucleation and immune infiltration.

Oropharyngeal squamous cell carcinoma (OPSCC), largely fueled by the human papillomavirus (HPV), has a complex biological and immunologic phenotype. Although HPV/p16 status can be used to stratify OPSCC patients as a function of survival, it remains unclear what drives an improved treatment response in HPV-associated OPSCC and whether targetable biomarkers exist that can inform a precision oncology approach. We analyzed OPSCC patients treated between 2000 and 2016 and correlated locoregional control (LRC), disease-free survival (DFS) and overall survival (OS) with conventional clinical parameters, risk parameters generated using deep-learning algorithms trained to quantify tumor-infiltrating lymphocytes (TILs) (OP-TIL) and multinucleated tumor cells (MuNI) and targeted transcriptomics. P16 was a dominant determinant of LRC, DFS and OS, but tobacco exposure, OP-TIL and MuNI risk features correlated with clinical outcomes independent of p16 status and the combination of p16, OP-TIL and MuNI generated a better stratification of OPSCC risk compared to individual parameters. Differential gene expression (DEG) analysis demonstrated overlap between MuNI and OP-TIL and identified genes involved in DNA repair, oxidative stress response and tumor immunity as the most prominent correlates with survival. Alteration of inflammatory/immune pathways correlated strongly with all risk features and oncologic outcomes. This suggests that development of OPSCC consists of an intersection between multiple required and permissive oncogenic and immunologic events which may be mechanistically linked. The strong relationship between tumor immunity and oncologic outcomes in OPSCC regardless of HPV status may provide opportunities for further biomarker development and precision oncology approaches incorporating immune checkpoint inhibitors for maximal anti-tumor efficacy.

Neoadjuvant Approaches to Non-Melanoma Skin Cancer.

Surgery and external-beam radiation therapy are the primary treatment modalities for locally advanced NMSC, but they can lead to impairment of function and disfigurement in sensitive areas such as the head and neck. With the advent of targeted systemic therapies and immunotherapy, physicians have explored the ability to offer neoadjuvant therapy for NMSC in order to reduce surgically induced morbidity. Provided herein is a guide to current applications of neoadjuvant systemic therapies for NMSC and future directions.

Deployment of cisplatin in Veterans with oropharyngeal cancer: toxicity and impact on oncologic outcomes.

Objective: Cisplatin forms the backbone of systemic chemotherapy treatment for oropharyngeal squamous cell carcinoma (OPSCC). The ideal cisplatin dosing regimen remains yet to be fully defined for achieving optimal efficacy and toxicity profiles in patients with comorbidity. Methods: We retrospectively reviewed oncologic and toxicity data for patients with OPSCC treated at the Michael E. DeBakey Veterans Affairs Medical Center between 2000 and 2020 who initiated curative intent, definitive chemo-radiation with one of three single agent regimens: high dose (HD) cisplatin, low dose (LD) cisplatin or cetuximab. Results: Patients with HPV-associated tumors and nonsmokers demonstrated improved overall and disease-free survival along with locoregional and distant metastatic control regardless of chemotherapy regimen. Regardless of regimen selection, patients which received a cumulative cisplatin dose ≥200 mg/m2 had a lower rate of distant metastasis. The HD regimen resulted in a greater fraction (75% vs. 50%) of patients receiving a cumulative cisplatin dose ≥200 mg/m2 and a comparable measured toxicity burden compared to the LD regimen. Conclusions: Both HD and LD cisplatin regimens can be safely delivered to a Veteran OPSCC patient population which should allow for straightforward application of conclusions drawn from completed and active clinical trials testing cisplatin regimens. Level of Evidence: 4.

Demographic and Tumor Characteristic Impact on Laryngeal Cancer Outcomes in a Minority Underserved Patient Population.

OBJECTIVE: Advanced laryngeal squamous cell carcinoma remains associated with approximately 50% mortality at 5 years. Delivery of multimodality treatment remains critical to maximizing survival for this disease, but achieving this at a national level remains a difficult undertaking, particularly in under- and uninsured patients as well as minority patients. We sought to evaluate laryngeal cancer treatment delivery and clinical outcomes in a predominantly minority and underserved cohort of largely under- and uninsured patients in a county hospital. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care county hospital in Houston, Texas. SUBJECTS AND METHODS: Patients (N = 210) with a new diagnosis of laryngeal squamous cell carcinoma treated between 2005 and 2015 were included in a retrospective analysis of patient demographics, tumor and treatment characteristics, and oncologic outcomes. RESULTS: The majority of patients presented with advanced disease (T4 = 43%, N>0 = 45%). Treatment selection was compliant with National Comprehensive Cancer Network guidelines in 81% of cases, but 76% of patients who required adjuvant radiotherapy were unable to start it within 6 weeks postsurgery. Overall survival and disease-free survival were 52% and 63% for the entire cohort, respectively. Supraglottic subsite and nodal metastases were significantly associated with decreased overall survival and disease-free survival. Race/ethnicity and insurance status were not associated with worse oncologic outcomes. CONCLUSION: Under- and uninsured patients often present with advanced laryngeal cancer. Oncologic outcomes in this cohort of patients is similar to that of other published series. Moreover, tumor characteristics rather than demographic variables drive oncologic outcomes for the predominantly minority and underserved patients seeking care in our tertiary care county hospital.

A Hidden Epidemic of "Intermediate Risk" Oropharynx Cancer.

OBJECTIVES: Oropharyngeal squamous cell carcinoma (OPSCC) incidence is rapidly increasing in the United States and around the world, driven in large part by infection with the human papillomavirus (HPV). HPV associated OPSCC (HPV+OPSCC) has been shown to have improved response to treatment relative to tobacco-associated OPSCC. However, improvement in patient survival has not been uniform. Subsets of OPSCC patients in the US and around the world continue to have poor oncologic outcomes. Although the drivers of this phenomenon remain unclear, there is increasing evidence that tobacco exposure plays an important role in modulating HPV+OPSCC clinical outcomes. METHODS: We conducted a review of the literature. RESULTS: We discuss the potential biological and epidemiological interplay between tobacco and HPV exposure in the context of OPSCC. Multiple retrospective and prospective cohorts show that HPV+OPSCC patients with a history of tobacco exposure have response to treatment and clinical outcomes distinct from HPV+OPSCC non-smokers which poses clinical and scientific challenges to be addressed over the next decade. CONCLUSIONS: The interaction between tobacco exposure and HPV infection in the context of OPSCC has significant implications for both standard of care treatment regimens and development of novel therapeutic approaches, in particular those which incorporate immunomodulatory agents. LEVEL OF EVIDENCE: 5.