Association of Periodontitis and Human Papillomavirus in Oral Rinse Specimens NHANES 2009–2012

Worldwide, head and neck carcinomas are the 6th most common cancer with an incidence of 400,000–500,000 annual cases,1–5 and nearly $3.2 billion in treatment costs. Even with aggressive treatment, there is significant morbidity and mortality.6 In 1983, human papilloma virus (HPV) was identified as a risk factor for oropharyngeal squamous cell carcinoma.7 Between 5–20% of head and neck squamous cell carcinomas and 40–90% of oropharyngeal carcinomas are related to HPV.1,8 There are over 150 different HPV types9 (or strains), most of which are not considered high risk types. The high risk types are: HPV-16, 18, 31, 33, 35, 45, 51, 52, 56, 68, 59, 68, 73, and 82.1 High risk HPV types have been found in nearly one-fourth of oral and laryngeal squamous cell carcinomas;10 HPV-16 was associated with 45–90% of oropharyngeal carcinomas.1,11 In contrast to the incidence of HPV negative (HPV−) oropharyngeal squamous cell carcinomas, HPV positive (HPV+) oropharyngeal squamous cell carcinomas have been increasing in incidence in the U.S.,12–15 from 0.8/100,000 in 1998 to 2.6/100,000 in 2004.8 HPV is an 8,000 base-pair DNA genome in an icosahedral 55nm capsid.16 The virus is small, non-enveloped, and epitheliotrophic.17 Although there is a growing awareness of the association of HPV and oropharyngeal squamous cell carcinomas, there is a lack of information about oral HPV infection and infectivity. D’Souza et al. reported that the prevalence of HPV-16 infection in exfoliated oral epithelial cells increased the odds of oropharyngeal carcinoma 13 times.18 Periodontitis is a complex chronic oral condition involving teeth, bone, epithelial cells, a biofilm community of bacteria, fungi, and viruses,16,19,20 and the immune system’s response to the biofilm community. Periodontitis has been associated with other chronic inflammatory diseases such as diabetes, and cardiovascular disease.15 In periodontitis, there is a continuous release of inflammatory cytokines and biomarkers which adversely affects systemic health,5 and is related to a modulation in epithelial barrier function protection. It is unknown if the biofilm and chronic inflammation of periodontitis with a decrease in epithelial barrier protection may be associated with oral HPV infectivity. The purpose of this study is to determine if there is an association of the presence of HPV in oral rinse specimens and periodontitis. The null hypothesis is that the odds ratio for the presence of HPV in oral rinse specimens is equal in individuals who have periodontitis as it is in individuals who do not have periodontitis. Previous studies have been equivocal. Some were limited by the use of self-reports for identifying periodontitis, others used self-reported oral health as the periodontal variable. Other studies have also had limitations as small sample sizes, or hospital-based cases. This study adds to the literature results from a large, nationally represented sample in which clinical assessment of all teeth was performed and the definition used for periodontitis was based on the definition for population surveillance of the Centers for Disease Control and Prevention in partnership with the American Academy of Periodontology.21