Human papilloma virus and tobacco-associated modulation of NOTCH1 pathway during development of head and neck squamous cell carcinoma clinical importance

Modulation of NOTCH1 pathway during development of head and neck squamous cell carcinoma (HNSCC) was evaluated with human papillomavirus (HPV) infection and/or tobacco habit to define the molecular mechanism of transformation of normal oral epithelium into neoplastic tissue. Differential expression pattern of the NOTCH1 pathway genes was seen in different datasets. In our HNSCC samples, high mRNA expression of NOTCH1, JAG1/2, HES1, HEY1 was seen with a significant increase particularly in NOTCH1 and HES1 expression in HPV+ ve (H+) samples. However, no such change in mRNA expression of FBXW7 was noted. In immunohistochemical analysis, high/medium expressions of activated NOTCH1 (NICD)/FBXW7/HES1 proteins were seen in basal/parabasal layers of adjacent normal oral epithelium than in the spinous layers with prevalent expression in H+ samples, followed by increased expression with the progression of the disease. A similar trend was seen in the H+ and/or tobacco+ve (T+) samples, except H-T- group. Infrequent copy number variation was seen in NOTCH1/JAG1/JAG2 loci in HNSCC samples. High/medium expression of NICD/HES1 protein showed overall poor patient outcome, though patients under H+ T– group showed better survival. Our data showed that activated NOTCH1 pathway in basal/parabasal layers of the oral epithelium was gradually aggravated during the development of HNSCC with a distinct association with HPV infection and tobacco habit. (author)