Head and neck squamous cell carcinomas (HNSCCs) are highly aggressive, multi-factorial tumors in the upper aerodigestive tract affecting more than half a million patients worldwide each year. Alcohol, tobacco, and human papillomavirus (HPV) infection are well known causative factors for HNSCCs. Current treatment options for HNSCCs are surgery, radiotherapy, chemotherapy, or combinatorial remedies. Over the past decade, despite the marked improvement in clinical outcome of many tumor types, the overall 5-year survival rate of HNSCCs remained ∼40–50% largely due to poor availability of effective therapeutic options for HNSCC patients with recurrent disease. Therefore, there is an urgent and unmet need for the identification of specific molecular signatures that better predict the clinical outcomes and markers that serve as better therapeutic targets. With recent technological advances in genomic and epigenetic analyses, our knowledge of HNSCC molecular characteristics and classification has been greatly enriched. Clinical and genomic meta-analysis of multicohort HNSCC gene expression profile has clearly demonstrated that HPV + and HPV - HNSCCs are not only derived from tissues of different anatomical regions, but also present with different mutation profiles, molecular characteristics, immune landscapes, and clinical prognosis. Here, we briefly review our current understanding of the biology, molecular profile, and immunological landscape of the HPV + and HPV - HNSCCs with an emphasis on the diversity and heterogeneity of HNSCC clinicopathology and therapeutic responses. After a review of recent advances and specific challenges for effective immunotherapy of HNSCCs, we then conclude with a discussion on the need to further enhance our understanding of the unique characteristics of HNSCC heterogeneity and the plasticity of immune landscape. Increased knowledge regarding the immunological characteristics of HPV + and HPV - HNSCCs would improve therapeutic targeting and immunotherapy strategies for different subtypes of HNSCCs.

This review suggests that survival estimates are similar between the two modalities and that the differences lie in adverse events.

HCCC has an overall good prognosis with potential for aggressive behavior. The presence of necrosis, locoregional disease, or positive margins is associated with risk for recurrence.

CT is not a reliable method for determining the presence of ECS in p16-positive HNSCC patients.

Objective Cancer of an unknown primary (CUP) squamous cell carcinoma metastatic to cervical lymph nodes is a challenging problem for the treating physician. Our aim is to determine if identification of the primary tumor is associated with improved oncologic outcomes and/or tumor characteristics including human papilloma virus (HPV) status. Study Design Retrospective, matched-pairs analysis contrasting 2 cohorts based upon discovery of primary lesion. Setting Tertiary teaching hospital. Subjects and Methods Records of 136 patients initially diagnosed as carcinoma of unknown primary were retrospectively reviewed (1980–2010) and divided into 2 cohorts based on discovery of the primary lesion. Primary outcome measures were overall survival and time to recurrence according to Kaplan-Meier analysis. A nested subset of 22 patients in which the primary was discovered were matched to 22 patients remaining undiscovered according to nodal stage and age. Results Discovered lesions were more likely to exhibit HPV positivity (P <.001). Matched-pairs analyses demonstrated that discovery of the primary was associated with better overall survival (HR = 0.125; 95% confidence interval [CI], 0.019–0.822; P = .030). Discovery of the primary was associated with improved cause-specific survival (HR = 0.142; 95% CI, 0.021–0.93; P = .0418) and disease-free survival (HR = 0.25; 95% CI, 0.069–0.91; P = .03). Conclusion HPV positivity is associated with discovery of the primary tumor. Discovery of the primary lesion is associated with improved overall survival, cause-specific survival, and disease-free survival in patients initially presenting as CUP in matched-pair and cohort comparison analyses.