A decade ago, a seminal study in the oropharyngeal cancer field 1 reported that there had been a 225% increase in incidence of human papillomavirus (HPV)-associated oropharyngeal cancer in the US between 1988 and 2004. Crucially, the authors projected that if trends were to continue, HPV-positive oropharyngeal cancer would surpass cervical cancer as the leading HPVassociated cancer in the US by 2020. 1 This prediction has since become a reality. 2 Between 2012 and 2016, HPV-associated oropharyngeal cancer indeed became the most common HPV-associated cancer in the US, and its incidence has surpassed cervical cancer, the disease for which the HPV vaccine was first developed and marketed. 3,4 In this issue of JAMA Otolaryngology-Head & Neck Surgery, the crosssectional study by Damgacioglu and colleagues 5 shines light on the trends in oropharyngeal cancer since the turn of the millennium using a relatively newly publicly available source of national data. They report that oropharyngeal cancer incidence increased nationally in the US between 2001 and 2017, especially among older adults. 5 This study by Damgacioglu et al 5 encompasses the introduction of the HPV vaccine in 2006, first approved and marketed for use in girls and then formally recommended for boys starting in 2011. 6 While there are at least 12 oncogenic strains of HPV found in the mucosa, HPV-16 and HPV-18 account for about 95% of all HPV-positive oropharyngeal cancer, and both HPV types have been covered by all HPV vaccines since 2006, including bivalent, quadrivalent, and the nonavalent vaccines now currently used in the US. 7 Several studies have shown the benefits of the HPV vaccine in preventing cervical intraepithelial neoplasia and cervical cancer. 8,9 In contrast, there is currently no approved screening for oropharyngeal cancer, and there are no universally accepted precancer targets. Hence, the current guidelines accept oral HPV prevention as an acceptable surrogate for oropharyngeal cancer, and that is currently the only primary cancer prevention for HPV-associated oropharyngeal cancer. 10 Damgacioglu et al 5 suggest that the HPV vaccine may also be making a difference in oropharyngeal cancer incidence. Between 2001 and 2016, there was a decrease in oropharyngeal cancer incidence among young males. While there is reason to be excited about the prospect of a primary prevention of oropharyngeal cancer through HPV vaccination, this still probably remains in the more distant future. Based on recent modeling studies, a significantly increased incidence of oropharyngeal cancer is projected in the next 2 decades. 11 The effect of HPV vaccination on the incidence of oropharyngeal cancer through 2045 is anticipated to