Clinicopathological Analysis of 1,000 Cases of Head and Neck Squamous Cell Carcinoma With Special Emphasis on Histological Variants and p16 Expression

Background: Head and neck squamous cell carcinoma (HNSCC) remains a major clinical and pathological concern in India.Its presentation varies by anatomical site and histological pattern, and recognizing uncommon variants, along with the appropriate interpretation of p16 expression, may provide useful diagnostic information.Objective: This study aimed to describe the demographic and clinicopathological profile of 1,000 HNSCC cases, with particular attention to histological variants, cervical lymph node involvement, and p16 expression.Materials and methods: This retrospective observational study included 1,000 histologically confirmed HNSCC cases diagnosed at a tertiary-care teaching hospital between January 2023 and December 2024.Age, sex, tumor site, histological grade, nodal status, histological variants, recurrence, and second primary malignancies were reviewed.p16 immunohistochemistry was performed in 109 cases with suitable tissue, including 50 conventional SCCs and 59 histological variants.Strong, diffuse nuclear and cytoplasmic staining in more than 70% of tumor cells was considered positive.Results: The cohort included 832 men and 168 women, with most patients aged 51-70 years.The oral tongue was the most frequent individual site (24.7%), while supraglottic and glottic tumors together accounted for 29.4% of cases.Well-differentiated SCC was the predominant grade (71.0%).Cervical lymph node metastasis was present in 147 patients (14.7%), with the highest within-grade frequency in moderately differentiated SCC (20.4%); the association between histological grade and nodal metastasis was significant (χ² = 9.89, p = 0.007).Of the 59 histological variants, 32 (54.2%) were p16 positive, with papillary SCC accounting for most positive cases.Of the 50 conventional SCCs, 20 (40.0%) showed p16 positivity.Twenty-five patients had second primary malignancies, and 16 had recurrence.Conclusions: This large single-center series demonstrates the clinicopathological diversity of HNSCC in an Indian tertiary-care setting.Histological variant recognition and assessment of nodal involvement remain important components of pathological evaluation.p16 immunohistochemistry may provide useful supplementary information in selected cases, but its expression should be interpreted as a surrogate marker rather than definitive evidence of HPV-driven disease without molecular confirmation.