Human papillomavirus (HPV) is a causative factor for tonsillar squamous cell carcinoma (TSCC) and patients with HPV positive (HPV⁺) TSCC have a better clinical outcome than those with HPV negative (HPV⁻) TSCC. However, since not all patients with HPV⁺TSCC respond to treatment, additional biomarkers are needed together with HPV status to better predict response to therapy and to individualize treatment. For this purpose, we examined whether the number of tumor infiltrating cytotoxic and regulatory T-cells in TSCC correlated to HPV status and to clinical outcome. Formalin fixed paraffin embedded TSCC, previously analysed for HPV DNA, derived from 83 patients, were divided into four groups depending on the HPV status of the tumor and clinical outcome. Tumors were stained by immunohistochemistry and evaluated for the number of infiltrating cytotoxic (CD8⁺) and regulatory (Foxp3⁺) T-cells. A high CD8⁺ T-cell infiltration was significantly positively correlated to a good clinical outcome in both patients with HPV⁺ and HPV^- TSCC patients. Similarly, a high CD8⁺/Foxp3⁺ TIL ratio was correlated to a 3-year disease free survival. Furthermore, HPV⁺TSCC had in comparison to HPV⁻TSCC, higher numbers of infiltrating CD8⁺ and Foxp3⁺ T-cells. In conclusion, a positive correlation between a high number of infiltrating CD8⁺ cells and clinical outcome indicates that CD8⁺ cells may contribute to a beneficial clinical outcome in TSCC patients, and may potentially serve as a biomarker. Likewise, the CD8⁺/Foxp3⁺cell ratio can potentially be used for the same purpose.

(2007). Vaccination, immune and gene therapy based on virus-like particles against viral infections and cancer. Expert Opinion on Biological Therapy: Vol. 7, No. 7, pp. 997-1007. doi: 10.1517/14712598.7.7.997

In 2007, human papillomavirus (HPV) type 16 was recognized as a risk factor by the International Agency for Research on Cancer, for oropharyngeal squamous cell carcinoma (OSCC), where tonsillar and base of tongue cancer (TSCC and BOTSCC) dominate. Furthermore, patients with HPV-positive TSCC and BOTSCC, had a much better clinical outcome than those with corresponding HPV-negative cancer and other head and neck cancer. More specifically, survival was around 80% for HPV-positive TSCC and BOTSCC vs. 40% five-year disease free survival, for the corresponding HPV-negative tumors with conventional radiotherapy and surgery, while this could not be observed for HPV-positive OSCC at other sites. In addition, the past 20–40 years in many Western Countries, the incidence of HPV-positive TSCC and BOTSCC has risen, and >70% are men. This has resulted in a relative increase of patients with HPV-positive TSCC and BOTSCC that may not need the intensified chemo-radiotherapy (with many more severe debilitating side effects) often given today to patients with head and neck cancer. However, before tapering therapy, one needs to enable selection of patients for such treatment, by identifying clinical and molecular markers that together with HPV-positive status will better predict patient prognosis and response to therapy. To conclude, there is a new increasing group of patients with HPV-positive TSCC and BOTSCC with good clinical outcome, where options for better-tailored therapy are needed. For prevention, it would be of benefit to vaccinate both girls and boys against HPV16 infection. For potential future screening the ways to do so need optimizing.