Oral cancer is a major global health problem with high incidence and low survival rates. The oral cavity contains biofilms as dental plaques that harbour both Gram-negative and Gram-positive bacterial antigens, lipopolysaccharide (LPS) and lipoteichoic acid (LTA), respectively. LPS and LTA are known to stimulate cancer cell growth, and the bioactive phytochemical capsaicin has been reported to reverse this effect. Here, we tested the efficacy of oral cancer chemotherapy treatment with capsaicin in the presence of LPS, LTA or the combination of both antigens. LPS and LTA were administered to Cal 27 oral cancer cells prior to and/or concurrently with capsaicin, and the treatment efficacy was evaluated by measuring cell proliferation and apoptotic cell death. We found that while capsaicin inhibits oral cancer cell proliferation and metabolism (MT Glo assay) and increases cell death (Trypan blue exclusion assay and Caspase 3/7 expression), its anti-cancer effect was significantly reduced on cells that are either primed or exposed to the bacterial antigens. Capsaicin treatment significantly increased oral cancer cells’ suppressor of cytokine signalling 3 gene expression. This increase was reversed in the presence of bacterial antigens during treatment. Our data establish a rationale for clinical consideration of bacterial antigens that may interfere with the treatment efficacy of oral cancer.

Oral cancer is the most common form of head and neck squamous cell carcinoma (HNSCC) and most frequently presents as oral squamous cell carcinoma (OSCC), which is associated with an alarmingly high mortality rate. Internationally, a plethora of research to further our understanding of the molecular pathways related to oral cancer is performed. This research is of value for early diagnosis, prognosis, and the investigation of new drugs that can ameliorate the harmful effects of oral cancer and provide optimal patient outcomes with minimal long-term complications. Two pathways on which the progression of OSCC depends on are those of proliferation and apoptosis, which overlap at many junctions. Herein, we aim to review these pathways and factors related to OSCC progression. Publicly available search engines, PubMed and Google Scholar, were used with the following keywords to identify relevant literature: oral cancer, proliferation, proliferation factors, genes, mutations, and tumor suppressor. We anticipate that the use of information provided through this review will further progress translational cancer research work in the field of oral cancer.

Oral biofilms harbour gram-negative bacterial antigen lipopolysaccharide (LPS) involved in oral cancer progression and gram-positive bacterial surface-associated adhesive, lipoteichoic acid (LTA). Thus, we hypothesised that LPS and LTA together would increase the proliferation of cancer cells compared to stimulation by LPS alone. Oral cancer cell lines SCC4, SCC9, SCC25, Cal 27 and the normal oral cell line, OKF6, were studied. The bacterial antigen stimulation indices were determined using the MT Glo assay. Cell proliferation after bacterial antigen stimulation was validated by clonogenic assays. Phosphokinase array, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and Western blot were employed to study proliferative and apoptotic pathways in bacterial antigen-stimulated cells. Bacterial antigens significantly stimulated Cal 27 (p ≤ 0.001) alone. SCC4 and SCC9 showed negligible stimulation with either antigen, while SCC25 results were comparable to OKF6. The combined antigen stimulation of Cal 27 led to a decrease in phosphorylated p53 and β-catenin and higher PI3K compared to LPS only stimulated cells (p ≤ 0.001). Combined bacterial antigen stimulation results in increased proliferation of Cal 27 cells due to lowering of tumor suppressor proteins and increased tumor proliferation-related proteins.

Breakthrough research in the field of immune checkpoint inhibitors and the development of a human papilloma virus vaccine triggered a plethora of research in the field of cancer immunotherapy. Both had significant effects on the treatment of head and neck squamous cell carcinoma. The advent of preclinical models and multidisciplinary approaches including bioinformatics, genetic engineering, clinical oncology, and immunology helped in the development of tumour-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR) T-cell therapy. Here, we discuss different immunotherapies such as adoptive T-cell transfer, immune checkpoint inhibitors, interleukins, and cancer vaccines for the treatment of head and neck cancer. This review showcases the intrinsic relation between the understanding and implementation of basic biology and clinical practice. We also address potential limitations of each immunotherapy approach and the advantages of personalized immunotherapy. Overall, the aim of this review is to encourage further research in the field of immunotherapy for head and neck cancer.

Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy, with an estimated 5-year survival rate of only 40–50%, largely due to late detection and diagnosis. Emerging evidence suggests that the human microbiome may be implicated in OSCC, with oral microbiome studies putatively identifying relevant bacterial species. As the impact of other microbial organisms, such as fungi and viruses, has largely been neglected, a bioinformatic approach utilizing the Trans-Proteomic Pipeline (TPP) and the R statistical programming language was implemented here to investigate not only bacteria, but also viruses and fungi in the context of a publicly available, OSCC, mass spectrometry (MS) dataset. Overall viral, bacterial, and fungal composition was inferred in control and OSCC patient tissue from protein data, with a range of proteins observed to be differentially enriched between healthy and OSCC conditions, of which the fungal protein profile presented as the best potential discriminator of OSCC within the analysed dataset. While the current project sheds new light on the fungal and viral spheres of the oral microbiome in cancer in silico, further research will be required to validate these findings in an experimental setting.