HERPES-SIMPLEX VIRUS AND HUMAN-PAPILLOMAVIRUS IN A POPULATION-BASED CASE-CONTROL STUDY OF CERVICAL INTRAEPITHELIAL NEOPLASIA GRADE II-III

In order to evaluate the association between seropositivity for herpes simplex virus (type 1 and type 2) and cervical intraepithelial neopla cia (CIN), we analysed data from a population-based case-control study of CIN grade II-III which included Norwegian women aged 20 to 44 year s, 94 cases and 228 controls. Our objectives were to determine if HSV- 1 and/or HSV-2 seropositivity were independent risk factors for CIN, t aking human papillomavirus exposure into account, and to elucidate the combined effect of HPV positivity and seropositivity for HSV. In logi stic regression analyses, the association between HSV-2 or HSV-I serop ositivity and CIN II-III was not explained by HPV (adjusted OR 3.0; 95 % CI 1.3-7.2 and adjusted OR 3.3; 95% CI 1.3-8.4, respectively). In an alyses restricted to HPV-16 DNA-positive individuals, seropositivity f or HSV-2 increased the risk of CIN (OR 11.1; 95% CI 1.2-105.7), wherea s HSV-1 seropositivity was not significantly associated with CIN. In w omen positive for other HPV types. only HSV-1 seropositivity was assoc iated with CIN (OR 8.5; 95% CI 1.3-55.8). In analyses of the HPV-16-se ropositive individuals, neither HSV-1 nor HSV-2 seropositivity was ass ociated with CIN. Compared to the reference group of jointly unexposed subjects, the HPV16 DNA-positive women who were anti-HSV-2 negative h ad an increased risk of CIN (OR 29; 95% CI 12-67), whereas the risk in women who were both HPV-16 DNA-positive and HSV-2 was OR=247 (95% CI 31-1996). The estimate of interaction was strong, but did not reach si gnificance, and our findings may suggest that the combined effect of t he two viruses is of aetiological importance in cervical carcinogenesi s. Furthermore, the results indicate that HPV DNA positivity is not su fficient to explain the sexual behaviour-associated risk of cervical n eoplasia and that further studies on the role of genital HSV (type 1 a s well as type 2) and other STDs are warranted.