Association Between Herpes Simplex Virus Type 2 and High-Risk Human Papillomavirus Infections: A Population Study of the National Health and Nutrition Examination Survey, 2009-2016

Abstract

Background: Human papillomavirus (HPV) is a leading cause of cervical cancer, with 14 subtypes classified as high-risk HPV (HR-HPV). Despite the availability of vaccines, certain regions still experience limited access. Herpes simplex virus type 2 (HSV-2), a common sexually transmitted infection, is hypothesized to increase the risk of HR-HPV infections. This study aims to individually analyze whether HSV-2 infection increases the risk of each HR-HPV infection in a representative sample of American adults.

Methods: Data were derived from the National Health and Nutrition Examination Survey from 2009 to 2016, involving 4076 female participants. The study utilized logistic regression to estimate the link between HSV-2 infection and HR-HPV infection. We also conducted a stratified analysis to evaluate the impact of HSV-2 on HR-HPV infection in different subgroups.

Results: After adjustment, the odds of having HR-HPV infection were 1.46 (95% CI, 1.24-1.71) for those with HSV-2 infection. Moreover, women with HSV-2 infection had higher odds of HPV-18 (odds ratio, 3.01; 95% CI, 2.05-4.41) and HPV-58 (OR, 2.05; 95% CI, 1.52-3.32) infection even after adjusting for potential confounding factors. The results remain significant in subgroup analysis and in the interaction test.

Conclusions: The study found a significant association between HSV-2 infection and HR-HPV infection, particularly with HPV-18 and HPV-58, highlighting the importance of preventing HSV infection and advocating for early vaccination with an HPV vaccine for those vulnerable to HSV infection. Further prospective studies are needed to validate causal associations and elucidate the underlying mechanisms.

Keywords: National Health and Nutrition Examination Survey; cervical cancer; herpes simplex virus type 2; high-risk human papillomavirus; sexually transmitted diseases.

Figure 1.

Flowchart of the population included in the final analysis. HPV, human papillomavirus; HSV-2, herpes simplex virus 2; NHANES, National Health and Nutrition Examination Survey.

Figure 2.

The relationship between HSV-2 infection and HPV-18 or HPV-58 infection according to basic features. Except for the stratification component itself, each stratification factor was adjusted for all other variables: age, race and ethnicity, education, marital status, family income, alcohol, smoke, HPV vaccine status, HIV status. HPV, human papillomavirus; HSV-2, herpes simplex virus 2; OR, odds ratio.