## 4 Discussions
The above papers support our 23.07% CMV prevalence detected and its possible role as a carcinogenic etiologic agent. Regarding MCV we detected a 30.76% MCV presence in the tested tumors. The analyzed studies are different regarding their findings. A research team from the Netherlands [37] tested polyomaviruses in patients with HNSCC non-smokers and non-drinkers using tissue microarrays and immunohistochemistry, and MCV was not detected in any of the cases. Another research team from Chile [38] assayed HNSCC using PCR and they detected MCV in 12.5% of tested cases. [PERSON] et al., from Finland, evaluated oropharyngeal tumors by Real-Time PCR and detected MCV in the tissue for one single person [39]. Besides the simple presence of MCV in the tumor tissues, other authors evaluated the role of this virus as a co-carcinogenic factor. [PERSON] et al., from Germany, tested and detected MCV in 10.0% of tonsillar squamous cell carcinomas, but the low viral load detected by real-time PCR did not support the role of polyomaviruses in tonsillar carcinogenesis [40]. [PERSON] et al. detected MCV by qPCR in 10.2% of the tonsillar carcinomas tested, with the same low viral load as the previous authors [41]. [PERSON] et al. analyzed all the polyomaviruses in oropharyngeal squamous cell carcinoma by PCR and they detected DNA of BKV, JCV and SV40, but the authors concluded that the presence of these viruses has no impact on survival [42]. Regarding HPV, it is well recognized by IARC that HPV 16 is involved in oropharyngeal carcinogenesis [5]. The fact that we did not detect any HPV-positive cases in this study was not a surprise for us, as we have already published two studies in which we did not find any HPV-positive case from 20 base of tongue cancers and tonsil cancers [43], and in a second larger study, we detected just 12.2%/189 cases HPV DNA positive, from which only 1.1% were HPV-driven (positive for HPV DNA and RNA) [44]. In a recent review published by [PERSON] et al. [12], the authors mention the considerable variation in HPV prevalence: 10% in Spain [45], and 70% in Sweden [46]. The authors reviewed the studies which used double HPV/DNA and p16 algorithms testing for oropharyngeal cancers. The same significant variation of HPV HNSCC positive cases worldwide was detected previously by two other research teams, with the suggestion that HPV 16 is very important mainly for oropharyngeal carcinogenesis [47; 48]. The beta HPV types were detected by a research team from the USA, using next-generation sequencing (NGS) from patients with oral cavity and oropharyngeal cancer cases [49]. [PERSON] et al. detected beta HPV types using Luminex-based assays and NGS in conjunctival squamous cell cancers [50]. The scientific literature cited above presented the results of studies realized for a single oncogenic virus or viruses from two viral families, using different diagnosis assays, including PCR, Real Time PCR, NGS, and immunohistochemistry. This brief review proves the difficult elements in the research of this issue, focusing on the possible involvement of viruses in the head and neck carcinogenic mechanism, and the limitations of current approaches. We detected an increased prevalence (88.5%) of the known oncogenic viruses, other than HPVs. These results are in line with others of our studies, in which we detected a low HPV prevalence in HNSCC [43; 44], on a more representative number of samples. For this category of patients, we could think of other risk co-factors, such as smoking (42.3%) and chronic alcohol consumption (38,4%), as the patients declared. The high prevalence of the other detected viruses (e.g., 61.63% EBV1, 30.76% MCV and 23.07% CMV) in these tumor samples could help to understand the mechanism of these cancers, and if this viral etiology could be confirmed, at least as co-factor. We need to mention that the simple presence of DNA of one known oncogenic virus is not proving the etiological role of that virus in a specific tumor tissue.