The most common risk factors for development of head and neck cancer (HNC) are tobacco, alcohol,microbial factors (high-risk human papillomaviruses, hrHPVs), systemic factors (immunosuppression, micronutrient deficiency) and UV-radiation.

There are approximately 600,000 new cases annually that accounts for 3-6% of all malignancies worldwide. In Croatia, there are about 1,000 new HNC cases annually representing 4.5% of all cancer cases. Despite aggressive treatment of HNC patients, which entails surgery, chemo- and radio-therapy, the five-year survival is only 40-50%.

HNC patients with HPV infection were found to have better prognosis and treatment response. Besides the HPV status, no adequate biomarkers have been found so far to predict the poor/good clinical outcome nor is the mechanism of how HPV modulates therapy response fully understood. Epigenetic changes such as DNA methylation of specific gene promoters and posttranscriptional modification of genes by specific microRNA (miRNA) seems to be promising biomarkers of disease occurrence and progression.

Therefore, the primary objective of this study is to identify novel specific epigenetic biomarkers to predict the treatment response or more reliably diagnose precancerous lesions and patients at greater risk for developing invasive cancer. This project is a comprehensive interdisciplinary research on the basis of HNC development and potential new approaches for their diagnosis and treatment.

This project, which includes basic and clinical research, will enable the improvement of existing knowledge and international competitiveness, development of new technological approaches in diagnostics and prognostics of HNC

Publications:

• Sabol I, Smahelova J, Klozar J, Mravak-Stipetic M, Gheit T, Tommasino M, Grce M, Tachezy R. Beta-HPV types in patients with head and neck pathology and in healthy subjects. J Clin Virol. 2016 Sep;82:159-65. doi: 10.1016/j.jcv.2016.07.019. Epub 2016 Jul 28
• Dediol E, Sabol I, Virag M, Grce M, Muller D, Manojlović S. HPV prevalence and p16INKa overexpression in non smoking non drinking oral cavity cancer patients. Oral Dis. 2016 Mar 19. doi:10.1111/odi.12476.
• Mravak-Stipetić M, Lončar-Brzak B, Bakale-Hodak I, Sabol I, Seiwerth S, Majstorović M, Grce M. Clinicopathologic correlation of oral lichen planus and oral lichenoid lesions: a preliminary study. Sci World J. 2014;2014:746874.
• Magdalena Grce, Ivan Sabol, Nina Milutin Gašperov. Poglavlje 2. Genetika i epigenetika tumora glave i vrata. Prgomet D (ur.), Tumori glave i vrata. Sveučilišni udžbenik. Medicinska naklada, Zagreb, 2018. p8-20 (University textbook, in Croatian)
• Ksenija Božinović, Ivan Sabol, Zoran Rakušić, Antonia Jakovčević, Mario Šekerija, Juraj Lukinović, Drago Prgomet, Magdalena Grce. Population differences influence human papillomavirus associated head and neck squamous cell carcinoma outcomes: a case of non-Western population. Plos One 2018 (in revision)
• Ksenija Božinović, Ivan Sabol, Emil Dediol, Nina Milutin Gašperov, Zuzana Vojtechova, Spomenka Manojlović, Ruth Tachezy, Magdalena Grce. Genome-wide miRNA profiling reinforces the importance of miR-9 in human papillomavirus associated oral and oropharyngeal head and neck cancer. Scientific Reports 2018 (in revision)
• Nina Milutin Gašperov, Ivan Sabol, Ksenija Božinović, Emil Dediol, Marinka Mravak-Stipetić, Danilo Licastro, Simeone Dal Monego, and Magdalena Grce. DNA methylome in head and neck cancer and oral lesions. Epigenetics 2018 (under review)