Zinc finger A20 and NF-[kappa]B correlate with high-risk human papillomavirus of squamous cell carcinoma patients

• Published in: Tumor biology 2014-12, Vol.35 (12), p.11855
• Main Authors: Tang, Ya-juan, Khalaf, Ahmad Taha, Liu, Xiao-ming, Xu, Chun-xing, Zhao, Wei, Cheng, Sai, Zhang, Ru-zhi
• Format: Article
• Language: English
• Subjects: Human papillomavirus; Proteins; Skin cancer
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1007/s13277-014-2416-9

Genital human papillomavirus (HPV) is associated with the development of cutaneous malignant tumors, and differences in HPV subtypes are found in several cancers by histology. NF-[kappa]B is persistently activated in most cancers and confers a survival advantage to cancer cells, while A20 is a critical negative regulator of NF-[kappa]B and is an important tumor suppressor inactivated in B cell lymphomas. This study was undertaken to identify HPV types in cutaneous squamous cell carcinoma (SCC) as well as to determine whether the crosstalk of A20/NF-[kappa]B was involved in HPV-induced SCC. Overall, HPV positivity was observed to be 66.2 %, with HPV16 being most common followed by infection with HPV18. Out of 43 HPV-positive samples, 35 samples were positive for one or more high-risk HPV (HR-HPV) types, suggesting a high association of SCC with HR-HPV infection, while only five HPV infections were detected in 21 normal skin samples and low-risk HPV (LR-HPV) infection was the most common. Both A20 and NF-[kappa]B were overexpressed in HPV-positive SCC samples (56 vs 87.4 %) and were closely correlated with TNM stage and lymph node transfer, respectively. More interestingly, the expression of A20 and NF-[kappa]B was much higher in HR-HPV samples than in LR-HPV samples. These results suggest that the crosstalk of A20 and NF-[kappa]B may contribute to HR-HPV-associated tumor growth and metastasis of SCC and may be a novel therapeutic target for SCC in the future.[PUBLICATION ABSTRACT]