Oropharyngeal cancer (OSCC) is increasing rapidly in incidence due to an increased incidence of human papillomavirus (HPV) positive tonsillar (TSCC) and tongue base (BOTSCC) squamous cell carcinoma. In addition, HPV positive TSCC and BOTSCC, but not other HPV positive OSCC, have been associated with a favorable clinical outcome. Despite the, in general, favorable outcome, all HPV positive TSCC and BOTSCC patients are today treated according to the same treatment protocols. We have previously identified prognostic markers e.g. high CD8+ tumour infiltrating lymphocytes (TILS) and low HLA class I expression, high LRIG1 etc, that with a high sensitivity identify HPV positive TSCC and BOTSCC patients with a favorable outcome, suggesting that a subset of these patients may benefit from a tapered treatment regime with maintained survival. However, the specificity is still low. Here the aim was to evaluate and to combine clinical and molecular markers into an algorithm for predicting outcome for individual patients with HPV DNA/p16(INK4a) positive TSCC and BOTSCC.
Previously 315 patients (197 as a training cohort and 118 as a validation cohort) treated curatively 2000-2011, with HPV DNA/p16INK4a positive tumors examined for HLA class I, CD8 tumor infiltrating lymphocytes (TILs) and other markers, were included in an L1-regularized logistic regression to evaluate the effect of the biomarker and clinical data, on 3-year risk of death or relapse. Presently, we are evaluating the samples for the presence of HPV E2 mRNA expression and hot spot mutations at different locations.
Preliminary data show on a pilot cohort of 117 patients, that the combination of high CD8+ TIL numbers and presence of HPV16 E2 mRNA is an excellent combination. The experimental data will shortly be completed in additional tumour samples with the aim to be included into the model for individual evaluation together with the other markers.
High CD8+ TIL numbers and presence of HPV16 E2 mRNA in HPV positive is the pilot study an excellent combination.