Search

Background: Despite reports of a link between human papillomavirus (HPV) infection and mechanistic target of rapamycin (mTOR) signaling activation, the role of the mTOR pathway, especially raptor and rictor, in HPV-related head and neck cancer is still unclear. The aim of the present study was to elucidate the role of the mTOR pathway in HPV-related oropharyngeal squamous cell carcinoma (OPSCC).Methods: The present study involved two strategies. The first was to investigate the activity of mTOR and mTOR-related complexes in high-risk HPV-positive (UM-SCC47 and CaSki) and HPV-negative (SCC-4 and SAS) cancer cell lines. The second was to elucidate mTOR complex expression in 80 oropharyngeal cancer tissues and to examine the relationship between mTOR complex expression and survival in patients with OPSCC.Results: The UM-SCC47 and CaSki cell lines showed high gene and protein expression of raptor. They also exhibited G1/S and G2/M phase cell cycle arrest following 24 h incubation with 6 μM temsirolimus, a rapamycin analog, and temsirolimus administration inhibited their growth. HPV-related OPSCC samples showed high gene and protein expression of raptor and rictor compared with HPV-unrelated OPSCC. In addition, HPV-related OPSCC patients with high raptor and rictor expression tended to have a worse prognosis than those with low or medium expression.Conclusions: These results suggest that raptor and rictor have important roles in HPV-related OPSCC and that temsirolimus is a potential therapeutic agent for patients with HPV-related OPSCC. This is the first report to reveal the overexpression of raptor and rictor in HPV-related OPSCC. [ABSTRACT FROM AUTHOR]

Among all patients, failure to achieve SB-EH was significantly associated with delayed treatment (over 2 years after diagnosis), B2 or B3 behavior, lack of treatment with immunomodulators, and patients not being treatment naïve ( I P i = 0.02, I P i = 0.02, I P i = 0.03, I P i < 0.01, respectively). 5 patients were needed surgical treatments and 10 patients required to optimize ongoing treatment. 51 patients had post-treatment lymph node size >=5 mm, and among those 33 (64.7%) patients had pathologically positive lateral nodes. During the following 5 years, the clinical recurrence occurred in 3 (11%) of the 27 patients with endoscopic score of i0 or i1, 4 (57%) of the 7 patients with i2, 3 (75%) of the 4 patients with i3, and 2 (100%) of the 2 patients with i4, showing a significant positive correlation ( I P i = 0.001) between the endoscopic severity and the clinical recurrence rate. B Results: b The median observation period was 40.2 months; 11 patients had endoscopic relapse, and 8 patients had early endoscopic relapse 6 months after surgery. [Extracted from the article]