IMPORTANCE OF HPV INVOLVEMENT AND FOXP3+ T-CELL STATUS AS PROGNOSTIC FACTORS IN TONSILAR SQUAMOUS CELL CARCINOMA

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Abstract

Background

Human papillomavirus (HPV) status is a strong and independent favorable prognostic factor for survival in tonsilar squamous cell cancer (TSCC). The reason for the improved survival in HPV-associated TSCC is unclear. Recently, activation of immune surveillance mechanism against non-self Ag is postulated to one of the reasonable causes as favorable prognosis of HPV associated with TSCC.

Methods

We reviewed the medical records of histologically confirmed locally advanced TSCC patients, curatively treated in Asan Medical Center from January 2000 to December 2008. The immunohistochemistry (IHC) assays for p16 and FOXP3 were done in TSCC pafaffin-embedded samples.

Results

We identified 79 patients who met the inclusion criteria. The median age was 54 years (range 32–76) and 16 (20%) patients were stage III and the others were all stage IV. With the median follow-up of 62.9 months (95% CI, 59.2–66.7), 63 (80%) were HPV-positive with p16 overexpression, and 38 (48%) were Treg-positive with FOXP3. Treg involvement was significantly related to HPV-positive status (P = 0.011). The result was the same after adjustment of age, T&N stage, smoking exposure and alcohol consumption. (Odd ratio = 6.54, 95% CI 1.58–27.1, P = 0.01.) Five-year overall survival (OS) rate in HPV-positive group was significantly higher than that of HPV-negative group (78% and 63%, hazard ratio (HR) = 0.347, 95% CI 0.14–0.87, P = 0.025), and 5-year OS of Treg-positive group was also higher than that of Treg-negative group (89% and 61%, HR = 0.158, 95% CI 0.05–0.53, P = 0.003). In multivariate analysis, the Treg status was an independent prognostic factor (HR = 0.11, 95% CI 0.03–0.40, P = 0.001), as well as HPV status (HR = 0.28, 95% CI 0.10–0.78, P = 0.016).

Conclusions

HPV positivity was associated with Treg positivity in TSCC and both were found to be favourable prognostic factors for survival.

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