Onkológia 4/2017

HPV-positive squamocellular oropharyngeal squamous cell carcinoma – influence of the molecular signature on the survival

Purpose: HPV-positive squamocellular oropharyngeal squamous cell carcinoma (OSCC) patients are favored for their better outcome and survival than HPV-negative patients. The etiopathogenetic factor of the OSCC is HPV after integration into the cell genome, expressing the E6/E7 viral oncogenes. The survival among favored HPV-positive patients varies and depends od cellular genes, that accelerate (KI67, TOP2A) or inhibit (CDKN1/ p21 and CDKN2A/p16) cell proliferation. Over-expression of KI67 and/or TOP2A without inhibition may increase the risk of disease progression and shorten the survival of favored HPV-positive patients. Material and methods: In a cohort of 30 OPC patients we observed: 1) the presence of HPV and the expression of E6/E7 viral oncogenes by RT-PCR, and 2) expression of cellular genes, so called molecular signature (KI67, TOP2A, CDKN1/p21 and CDKN2A/p16) and their effect on the survival of a favored group of patients. Results: Of 30 (100%) patients, HR-HPV 16 was detected in 7 (23.3%) patients. Of 7 (100%) HPV positive patients, we detected E6/E7 viral oncogenes expression in 5 (71.4%) patients and these patients belong to a group of favored OPC patients with a better prognosis. From 5 (100%) HPV E6/E7 positive patients with better prognosis, over-expression of the KI67 and TOP2A genes was detected in 4 (80%) patients, one of whom died in a shortened 2-year interval, 1 (20%) patient with a parallel breast cancer patient in therapy lives, and in 2 (40%) patients, despite the over-expression of KI67 and/or TOP2A show also over-expression of CDKN1/p21 and CDKN2A/p16 inhibitors and these patients live. Conclusion: Although we have analyzed a small cohort of patients, we can see the link between shortened survival of favored HPVpositive patient and over-expressed KI67 and TOP2A genes, that accelerate cell proliferation. Conversely, over-expressed CDKN1/p21 and/ or CDKN2A/p16 inhibitors may suppress the effects of KI67 and TOP2A. It is advisable to enlarge the patient cohort.

Keywords: oropharyngeal squamous cell carcinoma, HR-HPV16, E6/E7, TOP2A, KI67, CDKN1/p21, CDKN2A/p16