Risk of cervical cancer associated with Chlamydia trachomatis antibodies by histology, HPV type and HPV cofactors

Abstract

Human papillomavirus (HPV) is the central etiologic factor for cervical cancer, and prior studies suggested C. trachomatis may act as an HPV cofactor. We examined the C. trachomatis-cervical cancer association by serotype, histology, HPV type in the tumor, and other HPV cofactors. We conducted a population-based study in the Seattle-Puget Sound area of 302 women with invasive squamous cell carcinomas (SCC), 185 women with adenocarcinomas of the cervix (AC), and 318 HPV seropositive control women. The risk of SCC associated with antibodies to C. trachomatis was increased (OR 1.6, 95% CI 1.1-2.2) but not for AC (OR 1.0, 95% CI 0.6-1.5). This association was independent of HPV type in the SCC tumor tissue. There was an association between specific serotypes of C. trachomatis and SCC for 6 of the 10 serotypes: B (OR 3.6, 95% CI 1.5-8.4), D (OR 2.1, 95% CI, 1.2-3.5), E (OR 2.4, 95% CI, 1.4-3.9), G (OR 3.0, 95% CI, 1.1-7.9), I (OR 4.2, 95% CI, 1.5-11.7), and J (OR 2.3, 95% CI, 1.0-5.1), but not for the 4 types (C, F, H, and K) that were present at very low prevalence in this population. There was an increased risk of SCC, but not AC, associated with antibodies to C. trachomatis that was not serotype specific. ' 2006 Wiley-Liss, Inc.Key words: Chlamydia trachomatis; HPV; cervical cancer; histologic type; microimmunofluorescence Certain oncogenic genital human papillomavirus types (HPV) that are sexually transmitted have been shown to be a necessary but not sufficient cause of cervical cancer. 1 These oncogenic HPVs most often result in transient infections of the cervix, and only a small proportion of exposed women eventually progress to cervical cancer. 2 Since few women exposed to sexually transmitted HPV get cervical cancer, we are interested in cofactors in addition to HPV that promote the development of cancer. One such possible cofactor is Chlamydia trachomatis, which is highly prevalent among sexually active young women and can infect the cervix for long periods of time. Risk factors for C. trachomatis infection are similar to those for genital HPV infections, and include a history of multiple sexual partners, a recent new sexual partner, early age at first intercourse, and sporadic use of condoms or other barrier methods of contraception. 3,4 C. trachomatis often causes cervicitis, which is a chronic infection of the endocervical cells of the transformation zone. Such inflammation may predispose women to other STDs, including genital HPV infection, by damaging epithelial integrity. 5 Recent studies suggested that a history of C. trachomatis infection was associated with persistence of oncogenic HPV infections, 6,7 and other studies have shown that persistent HPV infections are necessary for progression to high-grade cervical intraepithelial neoplasia (CIN) and carcinoma. 2,8 Thus, chronic cervical inflammation by C. trachomatis could increase the risk of transformation of cervical cells that are persistently infected with oncogenic types of HPV.C. trachomatis antibodies are not used for clinical assessment of ...

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

“…In contrast, moderate and borderline associations were found with CIN3/CIS. History of CT infection has also been associated with CC in several previous studies [2][3][4]6 and it is assumed it increases the probability that HPV infections will become persistent, increasing thus the risk of neoplasia. 29,30 In contrast, a large prospective study based on the placebo arms of two multinational clinical trials of HPV vaccination found a moderate association between CT PCR positivity and CIN2 but not with CIN3.…”

Chlamydia trachomatis among women with normal and abnormal cervical smears in Lagos, Nigeria

“…7 Several studies in Nigeria have demonstrated an association between cervical cancer and C. trachomatis infection 7,[8][9][10][11][12][13][14] as it may possibly be one of the co-factors that promote the oncogenic potential of the HPV. [15][16][17] Chlamydia trachomatis, an obligate intracellular Gram negative bacterium, is one of the most common sexually transmitted disease agents. Its worldwide prevalence is 20-40% [18][19][20] with several studies in Nigeria showing equally high prevalence among the women in the reproductive age group 8,10 antenatal women 9,11 and individual with sexually transmitted infection in Nigeria.…”

Lack of Significant Effects of Chlamydia trachomatis Infection on Cervical Cancer Risk in a Nested Case-Control Study in North-East Thailand

“…While earlier studies found that a history of C. trachomatis infection was associated with cervical cancer (Anttila et al, 2001;Wallin et al, 2002;Smith et al, 2004;Madeleine et al, 2007), no statistically significant link was found with C.trachomatis IgG, IgA and IgM seropositivity in a recent study in Turkey (Onel et al, 2013) and there was no association between the presence of C. trachomatis DNA in cervical specimens and cervical cancer in Iran (Farivar and Johari, 2012). While the situation might be complicated by the possibility of a squamous cell limitation, C. trachomatis DNA being reported as absent in cervical adenocarcinomas (Quint et al, 2009), here we also did not find any association when such lesions were omitted from the analysis.…”