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In this issue of the Journal, Shield et al. [1] outline the leading role of human papillomavirus (HPV) in human cancers by identifying it as the leading infectious cause of cancers in France in 2015 with 6333 of the 352,000 new cancer cases identified over this year at the national level attributable to HPV [4580 new cancers in women (72.3% of the total) and 1753 new cancer cases in males (27.7% of the total)]. They reported that the three most prevalent HPV-attributable cancers in France were cervical cancers (2917 new cancer cases) followed by anal cancers (1458 new cancer cases) and oropharyngeal cancers (1371 new cancer cases) (Table 1) [1]. HPVs are ubiquitous DNA viruses divided into more than 200 genotypes grouped into five phylogenetic genera (Alpha, Beta, Gamma, Mu and Nu) and numerous different species [2, 3]. All HPV genotypes are adapted to specific human epithelial tissues [2]. Their transmission between humans mainly takes place through direct physical contact [2]. It is currently assumed that most human beings are infected with HPV throughout their lives [4] and that a person can acquire various HPV genotypes at the same time or sequentially [2]. Normally, immunological control is rapidly achieved and most HPV infections are eradicated in less than 2 years [2]. If not, most HPV infections are not responsible for any obvious diseases and result only in skin and mucosal lesions as benign papillomas and warts [2, 3]. However, if the infection is not properly controlled by the immune system, it can eventually be responsible for cancers. Indeed, 12 highly sexually transmitted HPV genotypes (HPV16/18/31/33/35/ 39/45/51/52/56/58/59) belonging to the Alpha genus are currently known to be responsible for cancers in both women and men [2, 3] and are now assumed to be responsible for 100% of cervical cancers, 88% of anal cancers, 78% of vaginal cancers, 51% of penile cancers, and 43% of vulvar cancers [5]. Recently, it was estimated that HPV infections resulted in 630,000 new cancers per year worldwide, the three most prevalent HPV-attributable cancers being cervical cancers (530,000 new cancer cases) followed by anal cancers (35,000 new cancers) and oropharynx cancers (29,000 new cancers) (Table 1) [6]. Historically, the main types of oncogenic HPV (HPV16 and HPV18) were found by identifying their DNA in cervical cancer biopsies in the 1970s led by Harald zur Hausen and colleagues [7]. This relationship enabled several discoveries to be made, including the role of HPV as a carcinogen at the cervix, the use of HPV-specific tests as part of cervical cancer prevention programs, and also made it possible to implement two highly efficient HPV vaccines (Gardasil and Cervarix ) [8] that are currently included in national vaccine schedules in more than 80 countries and have not, to date, been associated with any serious adverse events [9]. The discovery of these two vaccines, coupled with the fact that 83% of HPV-attributable cancers identified around the world are cervical cancers [6] making them the second leading cause of death from cancer in women around the world [10], has led public health actors to implement women-specific HPV vaccination programs with a significant decrease in cervical HPV infections and cancers in countries with established programs [9, 11]. In France, the women-specific HPV vaccination program was initiated in 2007 [12]. Prior to 2013, the HPV vaccination was recommended for 14 year-old girls with a catch-up vaccine for girls between the ages of 15 and 23 years old who had no sexual activity history or were in their first year of active sexual life [12]. In 2012, the French Vaccines Advisory Committee recommended that the HPV vaccination be administered to girls between the ages of 11 and 14, with a catch-up program up to the age of 20 [13]. In addition, since 2012, the French High Council for Public Health [Haut Conseil de Santé Publique (HCSP) in French] has recommended this vaccination for immunocompromised people at the national level [14]. Since then, the HCSP has published a report in which it recommends vaccinating Men who have Sex with Men (MSM) under the age of 26 who have had low numbers of sexual partners before being vaccinated [4]. However, despite all these & Didier Raoult [email protected]