Prognostic Significance of STING Immunoexpression in Relation to HPV16 Infection in Patients with Squamous Cell Carcinomas of Oral Cavity and Oropharynx

Abstract

Infection with HPV16 in cancers of the oral cavity (OCSCC) and oropharynx (OPSCC) is, today, an important etiological and prognostic factor. Patients with HPV-positive OPSCC have a better prognosis than uninfected patients. However, in over 40% of these patients, cancer progression is noticed. Their identification is particularly important due to the ongoing clinical trials regarding the possibility of de-escalation of anticancer treatment in patients with HPV-positive OPSCC. Some studies suggest that there is possibility to differentiate prognosis of HPV16-positive patients by STING (Stimulator of Interferon Genes) immunoexpression. The aim of the present study was to analyze the influence of STING immunoexpression on overall (OS) and disease-free survival (DFS) of patients with HPV16-positive and -negative OCSCC and OPSCC. The study was performed in a group of 87 patients with OCSCC and OPSCC for which in our earlier study active HPV16 infection was assessed by P16 expression followed by HPV DNA detection. To analyze STING immunoexpression in tumor area (THS) and in adjacent stromal tissues (SHS) H score (HS) was applied. In the subgroup with HPV16, active infection patients with tumors with THS had significantly better DFS (p = 0.047) than those without THS. In this subgroup, TSH did not significantly influence OS, and SHS did not significantly correlate with OS and DFS. In the subgroup of patients without active HPV16 infection, THS and SHS also did not significantly influence patients’ survival. Presented results indicated prognostic potential of tumor STING immunoexpression in patients with active HPV16 infection in cancers of oral cavity and oropharynx.

Antitumor effect of anti-vascular therapy with STING agonist depends on the tumor microenvironment context

“…It has been shown in cGAS- or STING-deficient mice that anti-PD-1 treatment failed to induce antitumor effects. The authors indicated that cGAS-STING signaling may need to be screened in patients before STING agonist application in combination with ICI ( 48 ). The efficacy of ICI was substantially increased in tumor models when combined with cGAMP in a cGAS-STING signal-sufficient context ( 49 ).…”

Prognostic significance of STING expression in solid tumor: a systematic review and meta-analysis

“…All eligible studies were retrospective and included STING expression of tumor cells ( Table 1 ). Four studies also included STING expression in stromal cells ( 33 , 39 , 41 , 43 ). Among these studies, the study by Biesaga et al.…”

“…All eligible studies were retrospective and included STING expression of tumor cells (Table 1). Four studies also included STING expression in stromal cells (33,39,41,43). Among these studies, the study by Biesaga et al examined STING expression of all stromal cells while three other studies examined its expression for immune cells only.…”

Expression Profiles of CDKN2A, MDM2, E2F2 and LTF Genes in Oral Squamous Cell Carcinoma

“…Bearing in mind the above results, it seems useful to investigate the status of HPV infection in our samples. However, the change in the expression of p16 (a protein encoded by CDKN2A) could be not only outcome virus infection but also DNA damage and gene mutation [ 15 ]. Tobacco smoke contains mutagenic substances [ 16 ], which could be related to our changes in CDKN2A expression in smokers.…”