Population-Wide Associations between Common Viral Pathogens and Self-Reported Arthritis: NHANES 2009-2012

Abstract

Objective: Persistent infectious agents have been implicated in chronic and recurrent inflammation, which may trigger or worsen many types of arthritis. Our objective was to determine whether exposure to herpes simplex virus (HSV) and human papillomavirus (HPV) is associated with self-reported arthritis among US adults.

Methods: We used data from two consecutive cycles of the National Health and Nutrition Examination Survey (NHANES) from 2009 until 2012 (N of examined adults ages 20-69 = 9483). Participants were classified as having arthritis by self-report. Viral serology for HSV-1 and HSV-2 and HPV PCR studies from oral rinse and vaginal swabs were available for analysis. We compared HSV-1 and HSV-2 seropositivity as well as oral and vaginal HPV DNA positivity between participants with self-reported arthritis vs. those without, adjusting for age, gender, race, income, education, BMI, and the use of immunosuppressive medications. We used three comparator outcomes, gout, kidney stones, and hypertension, to evaluate whether the associations were specific or not to arthritis.

Results: Arthritis was associated with older age, female gender, non-Hispanic White and Non-Hispanic Black race, higher BMI, and lower socioeconomic status. HSV-2 seropositivity, but not HSV-1 seropositivity, was independently associated with arthritis after adjustment for age, gender, race, income, education, BMI, and the use of immunosuppressive medications: AOR 1.48 (1.10-1.99). Oral HPV DNA positivity was also independently associated with arthritis: AOR 1.63 (1.17-2.28). After adjustment, there was no statistically significant difference in vaginal HPV DNA positivity between those with vs. those without arthritis: AOR 1.22 (0.90-1.66). There were no significant associations between viral exposures and any of the comparator outcomes.

Conclusions: HSV-2 seropositivity and oral HPV DNA positivity were associated with self-reported arthritis and not with comparator outcomes, after adjustment for multiple potential confounders. These findings should be confirmed in longitudinal studies.

Figure 1

The prevalence of positive viral markers and arthritis by age in the US population, NHANES 2009-2012. Viral studies were collected on the full study sample with pre-determined age cutoffs: HSV-1 and HSV-2 serologies: ages 20 to 49. Oral rinse for HPV DNA, ages 20 to 69, vaginal swabs for HPV DNA, ages 20 to 59. The prevalence of self-reported arthritis and viral markers in the population varied with age. Self-reported arthritis prevalence increased with age, from 3.4% in the 2^nd decade of life to 41.9% in the 6^th decade of life, which was the age range of this study (chi-square p value <0.001). HSV-1 and HSV-2 seropositivity increased with age (p <0.001) and oral HPV DNA positivity increased gradually up to the 5^th decade of life and then plateaued (p = 0.045). Vaginal HPV DNA positivity declined with age (p<0.001).