J Oral Pathol Med. 2026 Aug 16. doi: 10.1111/jop.70175. Online ahead of print.
ABSTRACT
BACKGROUND: Oral squamous cell carcinoma (OSCC) is a significant public health issue. While tobacco and alcohol are established risk factors, the role of human papillomavirus (HPV) in oral carcinogenesis remains debated. Cancer stem cells (CSCs) are implicated in tumor aggressiveness and therapy resistance. This study investigated the correlation between HPV infection, CSC marker expression (CD44, CD98, ALDH1), and clinicopathological parameters in tongue SCCs.
METHODS: A retrospective cohort of 1047 OSCC cases (2013-2018) was reviewed. From 452 tongue SCCs, 83 formalin-fixed paraffin-embedded specimens were randomly selected. HPV DNA detection was performed using qPCR with generic and type-specific primers (HPV 6, 11, 16, 18). Immunohistochemical expression of CD44, CD98, and ALDH1 was evaluated and quantified using digital image analysis (IHC Profiler). Statistical analyses included Kaplan-Meier survival curves, Kruskal-Wallis, Chi-square, and Spearman correlation tests.
RESULTS: HPV DNA was detected in 2/83 cases (2.4%): one HPV16-positive and one with co-infection (HPV6/18). CD44 expression was ubiquitously high, with no significant difference between -High and -Positive categories (p > 0.9999), but both were significantly higher than -Low and -Negative scores (p < 0.0001). ALDH1 exhibited a focal staining pattern. The ALDH1-High score was significantly less frequent than -Positive and -Low scores (p < 0.01) and showed a significant positive correlation with both advanced clinical stage (Spearman r: 0.5062; p = 0.0007) and higher tumor grade (Spearman r: 0.3352; p = 0.0322). CD98 was not detected. An inverse correlation was observed between HPV and clinical staging (Spearman r: -0.2377; p = 0.0305); however, due to the low number of HPV-positive cases, this finding must be interpreted with caution.
CONCLUSION: Our findings suggest a distinct CSC expression profile in this cohort, characterized by ubiquitous CD44 expression and a rare but highly aggressive ALDH1-High subpopulation, concomitant with low HPV detection. The strong positive correlation of ALDH1-High score with advanced stage and grade highlights its potential role as a key driver of tumor aggression, warranting further investigation as a prognostic marker.
PMID:42604793 | DOI:10.1111/jop.70175
