Seroprevalence of human papillomaviruses and Chlamydia trachomatis and cervical cancer risk: nested case–control study

Abstract

A nested case-control study of invasive and in situ cervical cancer was performed within a community-based cohort of 13 595 Taiwanese women assembled in 1991, with a follow-up period of 9 years. Baseline serum or plasma samples were analysed for antibodies against human papillomavirus (HPV) types 6, 16 and 18 and Chlamydia trachomatis. In total, 114 cases (42 incident cases identified during follow-up and 72 prevalent cases identified at baseline) and 519 matched controls were included in the study. HPV-16 seropositivity was strongly associated with cervical cancer (OR56.33; 95 % CI 3. 45-11.62). Overall, C. trachomatis was not associated with cervical cancer, but was associated with cervical cancer in analyses restricted to incident cases of cancer (OR52.94; 95 % CI 1.17-7.42) or to cases in which serum samples were analysed (OR53.13; 95 % CI 1. 16-8.47). An antagonistic interaction between HPV-6 and -16 was found in a multiplicative model. These results suggest that different HPV types might interfere in cervical carcinogenesis and that C. trachomatis is associated with cervical cancer in prospective studies, and support the notion that HPV-16 seropositivity is strongly associated with cervical cancer. INTRODUCTIONCervical cancer is the most common cancer among women in Taiwan, with an age-standardized incidence rate of 22.1 per 100 000 person-years compared with a mean of 11.2 in developed countries (Parkin et al., 1993;Wang & Lin, 1996a). It is well established that the major cause of cervical cancer is persistent infection with oncogenic genital human papillomavirus (HPV) (Walboomers et al., 1999) and that both cervical cancer and HPV infection are associated with high-risk sexual behaviour Silins et al., 2002). The HPV type distribution varies among geographical regions but, worldwide, HPV-16 is the most common HPV type in cervical cancer (Clifford et al., 2003; Nauclér et al., 2004).As the majority of HPV infections are transient (Evander et al., 1995; Hildesheim et al., 1994;Ho et al., 1998), viral genome detection is an imperfect marker of past HPV infection (Olsen et al., 1997). However, HPV antibody levels have been shown to be stable over time, even after more than a decade of follow-up (af Geijersstam et al., 1998;Shah et al., 1997), and correlate with life-time cumulative HPV exposure (Shah et al., 1997;Wang et al., 1997). Prospective seroepidemiological studies have found that the presence of IgG antibodies against HPV-16 is associated with an increased risk of cervical cancer (Shah et al., 1997;Wang et al., 1997), in particular in low-sexualrisk-taking populations Lehtinen et al., 1996).In spite of the fact that exposure to oncogenic HPV increases with the number of sexual partners, there is no excess risk of developing cervical cancer in patients with a history of condylomata acuminata, which is caused by sexually transmissible infections with the benign HPV types 6 and 11 (Sigurgeirsson et al., 1991). A possible explanation is that benign HPV types might interfere with the oncogenicity of high...

Prospective seroepidemiologic study on the role of Human Papillomavirus and other infections in cervical carcinogenesis: Evidence from the EPIC cohort

“…These findings are largely consistent with those from several other prospective and retrospective studies associating serological markers of past HPV exposure with CC risk. 6,[18][19][20][21] The contribution of our study with regard to HPV serology is, in addition to the large sample size and the prospective design, the use of a wide panel of type-specific HPV markers that includes L1, E6, and E7 proteins and a high number of HPV types: Nine mucosal and four cutaneous.…”

Order of HPV/Chlamydia infections and cervical high‐grade precancer risk: A case‐cohort study

“…This very high risk of immediate cervical precancer associated with incident, virtually concomitant acquisition of C. trachomatis and HPV18=45 infections is in line with the active role of C. trachomatis in the development of cervical precancer. 5,8 Even if C. trachomatis is not present in cervical adenocarcinomas, 19 it may cause local immune perturbation in the upper genital tract and thus facilitate HPV18=45 associated cell transformation during carcinogenesis.…”

“…3 Smoking and Chlamydia trachomatis are HPV16 independent risk factors for ICC and CIN3, 4,5 while HPV types 6 and 11 lower the risk associated with HPV16. [6][7][8] It is not known whether infections with a low-risk HPV or C. trachomatis need to precede hrHPV infections or not to exert their effects. Moreover, the superior carcinogenicity of HPV16 has made it difficult to study whether or not order in the chain of events matters.…”

Chlamydia trachomatis and human papillomavirus coinfection: association with p16INK4a and Ki67 expression in biopsies of patients with pre-neoplastic and neoplastic lesions

“…In a study 19 with 114 cases, where 72 were incident and 42 were prevalent at the study entrance, HPV-16 seropositivity was associated with cervical cancer (OR = 6.33, 95% CI: 3.45-11.62). In general, the CT infection was not associated with the cervical cancer; however, there was an association when incidental cases were evaluated (OR = 2.94, 95% CI: 1.16-8.47).…”

“…In general, the CT infection was not associated with the cervical cancer; however, there was an association when incidental cases were evaluated (OR = 2.94, 95% CI: 1.16-8.47). 19 The p16INK4a expression has been mentioned 5,6 as a promising marker for HR-HPV-induced lesions. However, studies did not evaluate if its expression is increased in HPV and CT coinfection.…”