## 4 Discussion
### OPSCC HPV DNA Positive, p16, Risk Factors  
The pattern of OPSCC cancers is a research topic for many authors. We carried out an analysis of the recently published articles which are referring to HPV-positive OPSCC.  
A research team from the Johns Hopkins University analyzed a comprehensive number (more than 13,000) of these types of cancers, HPV-positive, for twelve years. The authors found that the BOTSCC and TSCC are different from an epidemiological point of view, and they identified risk factors such as: age over 70, white race, male gender, and tonsillectomy [30]. Authors from Belgium analyzed 131 patients over a period 10 years (2007-2017) and concluded that p16 expression was associated with a better evolution of the disease. Besides p16, the authors included smoking and chronic alcohol use in their prognostic significance score [31]. Smoking was also taken in consideration as a risk factor for survival of HPV-positive oropharyngeal cancers, by a team from the USA. The authors found that for a smoking status of more than 10 pack/year, the effect on five-year overall survival was significant, and therefore they considered that smoking should be taken in consideration by The American Joint Committee on Cancer (AJCC), in the staging system of HPV-positive oropharyngeal cancer [32]. [PERSON] et al., used a recently developed HR-HPV (high-risk human papillomavirus) mRNA silver in situ hybridization (SISH) assay for detecting HPV16, HPV18, and HPV33 in HPV DNA positive oropharyngeal cancers, as it is known that the transcriptional activity of HR-HPV within oropharyngeal squamous cell carcinomas has been linked to improved survival of the patients. The authors found an 80% sensitivity of this new method, which supports the need for further studies using this assay [33]. Another survival marker of HPV-positive OPSCC was considered to be HPV16 viral load by Japanese authors, as it is also thought to be for cervical cancer [34]. In Brazilian HPV+ OPSCC patients, [PERSON] et al., identified tumor staging, tumor localization, smoking, level of education, and gender as prognosis factors. The authors suggest that these factors could be used for a better stratification and management of this category of patients [35]. A research team from Lyon used p16/p53 algorithm to predict HPV tumor status in OPSCC, and authors from Germany concluded that tobacco, alcohol abuse, age, and gender should be added to the current UICC (The Union for International Cancer Control) staging system to improve the risk stratification in HPV+OPSCC [13; 36]. [PERSON] et al. from Amsterdam evaluated the health-related quality of life for HPV-positive OPSCC patients. For the very pragmatic question, \"Does HPV status matter?\", the authors found that HPV-positive OPSCC patients had a better score before treatment, recovered faster, and had a different course of emotional functioning, in comparison to HPV-negative patients [37]. A research team from Denmark investigated, in a review study, the impact of specific HPV genotypes on survival in HPV+ OPSCC and identified a favorable prognosis among patients with HPV16 OPSCC compared with HR non-HPV16 OPSCC [38].