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Background  Herpes simplex virus types 1 and 2 (HSV1 and HSV2) are infectious agents, and their association with cancer occurrence in human is a controversial topic for decades. We addressed this subject using all available continuous National Health and Nutrition Examination Survey (NHANES) cross-sectional data from 1999 to 2014.    Methods  Eight data cycles (1999–2000, 2001–2002, 2003–2004, 2005–2006, 2007–2008, 2009–2010, 2011–2012, and 2013–2014) were employed, and a sample of 8184 female participants was used in this study according to the availability of cancer history and HSV serostatus.    Results  The seroprevalences of HSV1 and HSV2 were 60.73 ± 0.89 and 25.02 ± 0.64, respectively, and the numbers increased with age ( P  < 0.01). In confounder-adjusted logistic regression analysis, association between HSV1 seropositivity and uterine cancer was identified (adjusted odds ratio-OR adjusted  = 6.03; 95% CI: 1.52, 23.87). HSV2 seropositivity was associated with cancer occurrence (OR adjusted  = 1.47; 95% CI: 1.01, 2.14), cervical cancer (OR adjusted  = 1.72; 95% CI: 1.06, 2.79) and uterine cancer (OR adjusted  = 3.49; 95% CI: 1.03, 11.85). Moreover, HSV2 was persistently associated with cervical cancer after further adjusting high-risk human papillomavirus (HPV) as confounder (OR adjusted  = 1.90; 95% CI: 1.09, 3.34). Relative risk (RR)-based interaction measurement between HSV2 and HPV on the additive scale suggests higher RR for cervical cancer in participants with seropositivity for HPV only (RR adjusted  = 2.98; 95% CI: 1.23, 7.20;  P  = 0.02), HSV2 only (RR adjusted  = 2.79; 95% CI: 1.31, 5.96;  P  = 0.01) or both viruses (RR adjusted  = 3.44; 95% CI: 1.50, 7.86;  P  < 0.01) when setting participants with seronegativity for both HPV and HSV2 as reference.    Conclusions  The finding of current study provides epidemiological evidence that serostatus of HSV2 can serve as an independent predictor for cervical cancer.    Electronic supplementary material  The online version of this article (10.1186/s12885-017-3734-2) contains supplementary material, which is available to authorized users.

Seropositivity to herpes simplex virus type 2, but not type 1 is associated with cervical cancer: NHANES (1999–2014)