## 1 Introduction  
Human papillomavirus virus (HPV) is recognized by the International Agency for Research on Cancer (IARC) as a biological agent involved in carcinogenesis as main co-factor. From all high-risk HPV types known to be involved in cervical cancer, only HPV16 was recognized as having an etiological role in oropharyngeal cancers and tonsil cancers [1]. HPV-driven head and neck squamous cell carcinomas (HPV-driven HNSCC) represent different malignancies, in comparison to cervical cancer. For cervical cancer types, for which HPV is recognized as a necessary cause, well-known screening methods (e.g., Pap test, and clinically validated high risk HPV DNA tests) are available, and together with the availability of the three vaccines (bi, tetra, and nonavalent), there is hope for cervical cancer elimination [2,3]. For HPV-driven HNSCC, clinically validated screening methods and therapeutic strategies are not yet established, as these categories of cancers are very heterogenous (oral cavity, orophnx, pharynx, and larynx/hypopharynx). Information is still needed, regarding the understanding of the temporal and geographic differences in HPV-driven oropharyngeal squamous cellular cancers (OPSCC) incidence, as well as regarding the risk factors and if they change over time. A recent study from the USA revealed an increased proportion of middle-aged patients with oropharyngeal cancer, which reflects the increase in HPV-related cancers [4]. The same increasing trend was published by the Dalianis HNSCC group, which detected a 70% HPV prevalence in TSCC/BOTSCC in Stockholm [5]. The epidemiology and natural history of oral HPV infection is important to be known. Similarly with the research realized for precancerous lesions in case of cervical cancer, it is necessary to analyze the precursor lesions of HPV-driven OPSCC. For example, [PERSON] et al., identified significant differences in protein expression for SPARC, psoriasis, type I collagen, and galectin-1 in both HPV+ and HPV\(-\) TSCC/BOTSCC, being one of the first studies which examined the differences in gene expression between dysplastic and invasive HPV+ and HPV\(-\) TSCC/BOTSCC [6]. Another biomarker is fibroblast growth factor receptor 3 ( FGFR3), which has been identified as a potential target for therapy of HNSCC. By NGS (next generation sequencing), FGFR3 was found mutated in 15% of Norwegian HNSCC samples analyzed. This finding confirms the possibility of advanced personalized treatment, using targeted therapy against FFR3 [7]. Besides FGFR3, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3 CA) was found to be most commonly mutated in HNSCC. Both these gene mutations are used to identify new therapeutic targets and further our understanding of existing ones [8]. Erdafitinib and pemigatinib, two FGFR selective inhibitors targeting FGFR fusions, have been approved by the U.S. Food and Drug Administration (FDA) to treat patients with urothelial cancer and cholangiocarcinoma carcinoma, respectively [9,10], and there is hope that these inhibitors could be used for HNSCC also. To identify patients at risk of severe evolution, testing for specific biomarkers is necessary, to relate to clinical practice. Recent studies from the USA note the changing therapeutic trends for advanced HPV-positive OPSCC: the percentage of HPV positive patients treated with surgery-based therapy decreasing by half, in the group of patients targeted by the study, during the period 2010-2016 [11]. [PERSON] et al., from Cambridge, evaluated, in a Cochrane review, the randomized controlled trials regarding the effects of de-intensified adjuvant (chemo)radiotherapy in comparison to standard adjuvant (chemo)radiotherapy in patients with resectable HPV-positive OPSCC, as it is known that HPV-positive OPSCC patients are often younger and have a significantly improved survival relative to HPV-negative patients.