Regulation of Interleukin‑6 in Head and Neck Squamous Cell Carcinoma Is Related to Papillomavirus Infection

The prevalence of head and neck squamous
cell carcinoma (HNSCC)
related to human papillomavirus (HPV) is increasing, unlike tobacco-
and alcohol-associated cancers. To gain a clearer understanding of
the molecular mechanisms implicated in HNSCC, depending on the presence
or not of a viral sequence, we investigated the expression of proteins
detected in the tumor regions of HNSCC patients. Twenty-two untreated
HNSCC patients were selected according to the presence of HPV-16.
For six patients, tumor and controlateral healthy tissues were tested
for viral detection before quantitative proteomic analysis. After
confirmation by Western blot, proteins were connected into a network,
leading to investigate interleukin-6 (IL-6) by immunocytochemistry
and ELISA. 41 ± 5% of proteins quantified by proteomics were
differentially expressed in tumor compared with healthy regions. Among
them, 36 proteins were retained as modulated in HPV-16 positive or
negative tumors, including cytokeratins, tubulins, annexin A1, and
serpin B1. Network analysis suggested a central role of IL-6, confirmed
by
overexpression of IL-6 in tumor tissues as in sera of HPV-negative
HNSCC compared with HPV-16-positive tumors. This modulation may contribute
to the survival and proliferation of cancer cells, although it was
not related to tumor stage or to the level of HPV-16 DNA.