Article
ALDH1-positive cancer stem cells are associated with HR-HPV+/p16+ expression in HNSCC
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Published: | April 4, 2012 |
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HPV-associated head and neck squamous cell carcinoma (HNSCC) affect a younger patient population with relatively little comorbidity. Therefore, sustainable therapeutic results with few long term side effects are highly desirable. ALDH1 has been confirmed as a marker for cancer stem cells (CSC) of HNSCC. The main etiology of HNSCC is either a persistent infection with high-risk HPV (HR-HPV) or longterm substance abuse. For this study we investigated possible associations between HR-HPV/p16, CSC-frequency and clinical parameters.
27 pairs of primary HNSCC and metastases were typed for HPV. The positivity for ALDH1 and p16 was determined by IHC. Statistical analyses explored the relationship of ALDH1, HPV and p16 with clinical outcome.
31.5% (17/54) of cases were found to be positive for HPV, 22.2% (12/54) were positive for p16 and 79.63% (43/54) were positive for ALDH1. Statistical analysis showed a strong positive association of ALDH1 expression with HPV (P=0.005, OR=2.7, 95% CI=1.352-5.393) and p16 (P=0.009, OR=2.807, 95% CI=1.287-6.12). In primary tumors, ALDH1 expression was positively correlated with tumor grade (P=0.013) and tumor stage (P=0.041). Further analysis demonstrated that ALDH1 expression was elevated in metastases compared to primary tumor (P=0.006).
ALDH1-positive putative CSC are more frequently present in HR-HPV/p16+-asscociated HNSCC. Moreover, these data demonstrate the expression levels of ALDH1 are associated with tumor grade and progression of metastasis. Therefore, measuring ALDH1 levels of patients with HNSCC may have a prognostic value. Moreover our findings may have an impact for the development of broadly applicable vaccination targeting HR-HPV and ALDH1.