High Level of Tregs Is a Positive Prognostic Marker in Patients with HPV-Positive Oral and Oropharyngeal Squamous Cell Carcinomas

Abstract

Background. Human papillomaviruses (HPVs) have been proved as one of the etiological factors of oropharyngeal squamous cell carcinoma (OPSCC). Patients with tumors of viral etiology have a lower recurrence rate and better prognosis. OPSCC is linked to an alteration in the immune system. Only a limited number of studies have correlated both the immunological parameters and HPV status with patient prognosis. The aim of this study was to determine whether HPV infection and the immunological status influence patient prognosis individually or in concurrence. Material and Methods. Sixty patients with oral and oropharyngeal carcinomas were enrolled. They were divided into HPV-positive and HPV-negative groups based on the expression of HPV 16 E6 mRNA. Basic lymphocyte subpopulations were determined in the peripheral blood by means of flow cytometry. Results. Significantly better disease-specific survival (DSS) was observed in patients with HPV-positive tumors. Nodal status, tumor grade, recurrence, and CD8+/Tregs ratio were identified as factors influencing DSS. A higher level of Tregs and a lower ratio of CD8/Tregs influenced overall survival (OS) independently of HPV status and age. Patients with HPV-positive tumors and high levels of Tregs survived significantly better than patients from the other groups. Conclusion. Better survival is associated with HPV positivity and elevated Tregs levels. Our data suggest that HPV infection and Tregs do not influence patient prognosis in concurrence.

Differences in T-cell infiltrates and survival between HPV+ and HPV- oropharyngeal squamous cell carcinoma

“…Of the included studies, seven articles investigated the relation between HPV status and circulating T cells, using flow cytometry. Four of these studies also studied the HPV-specific T-cell response and HPV status [1,5,6,11,14,18,19]. The relation between tumor infiltrating lymphocytes (TILs) and HPV status was the subject of research in 12 studies, using immunohistochemistry [2–4,7–10,15–17,20].…”

“…In addition, one of these articles described a significant decrease in naïve T cells and significant increase of effector T cells and effector memory T cells in HPV+, compared with HPV- OPSCC [18]. Two other articles showed that circulating CD4+ cells were decreased in HPV+ OPSCC, compared with HPV- OPSCC, although this was not significant [5–9,14,18,19]. In contrast, one article showed an increase of CD4+ cells, but again this was not significant [11].…”

“…Studies were excluded when [1] they did not contain original data, [2] it were posters, reviews, opinion papers or abstracts, [3] based on animal studies, [4] the investigated subsite was not the oropharynx, [5] did not describe the relationship between T lymphocytes and HPV status in OPSCC (Figure 1). …”

“…In the last decades, preventive strategies have led to a decrease in HNSCC, mainly of hypopharyngeal and laryngeal SCC. In contrast, there has been a growing proportion of oropharyngeal squamous cell carcinomas (OPSCC) in the USA and Europe in individuals who neither drank nor used tobacco [5]. These were mainly young, white men who are positive for HPV, in particular type 16 [6].…”

The emerging role of immunotherapy in head and neck squamous cell carcinoma (HNSCC): anti-tumor immunity and clinical applications

“…Several studies have demonstrated an increased population of CD8+ lymphocytes, Tregs and increased CD8+/Treg ratio in HPV+ OPC, which are associated with improved prognosis (31,32).…”