Oral Oncology 51 (2015) e8–e9
Contents lists available at ScienceDirect
Oral Oncology journal homepage: www.elsevier.com/locate/oraloncology
Letter to the Editor Chlamydia trachomatis infection: Possible cofactor for oropharyngeal cancer development?
The preponderance of evidence shows that nearly all cervical cancers and many oropharyngeal cancers (OPCs) are due to human papillomavirus (HPV) infection [1–3]. However, only a small proportion of women infected with HPV, even high risk variants such as 16 and 18, progress to invasive cancer [4]. Chlamydia trachomatis (CT) co-infection is believed to be a possible co-factor that tips the balance from infection to oncogenesis [5,6]. Positive associations have been observed between CT infection and squamous cell carcinoma of the cervix or its precursor lesions in most [7–14], but not all [15–17], previous epidemiologic studies that controlled for HPV infection. By analogy, we propose that CT infection may also be a cofactor for HPV-associated OPCs. CT has been extensively studied as a sexually transmitted infection (STI), most often associated with genital and anal sites of infection. In both the US and globally, CT is the most common bacterial STI with an estimated 2,860,000 and 105,700,000 cases, respectively, in 2008 [18,19]. HPV (all variants) is the most common STI with an estimated 79 million Americans currently infected, and lifetime risks of HPV acquisition for those with at least one opposite-sex partner of 84.6% for females and 91.3% for males [20,21]. There is considerable opportunity for oral infection, as while approximately three quarters of US individuals engage in oral sex, condoms are used only 6–10% of the time and oral infection prevalences range from 1.5–12% (CT) and from 2.3–7.6% (HPV) [22–29]. Given that both CT and HPV are obligate intracellular organisms, prefer similar tissues, and are both transmitted via sexual contact, it is not surprising that they may co-occur within a single individual [6,30,31]. Chlamydial infection may contribute to carcinogenesis by its possible impact upon host cell structure, gene regulation and maintenance. Infected cells experience substantial epithelial disruption, increased and unrepaired DNA double-strand breaks due to CT-induced reactive oxygen species, increased oncogenic signaling, continued proliferation, and inhibition of apoptosis [32–36]. The main tissue targets of both chlamydia and HPV are the epithelial cells lining mucosal surfaces, and such tissues are important mediators of organism immune response [37–39]. Chlamydia infection may lead to chronic persistent inflammation, itself associated with rapid cell division, debilitated DNA repair, oxidative stress, increased levels of prostaglandins and cytokines, inflammatory pathway stimulation/upregulation, and oncogenesis [40–45]. As infection-driven inflammation has been implicated in 15–20% of cancers, these data support the hypothesis that chlamydial infection may contribute to oncogenesis [46]. Epidemiological data show that HPV-associated OPCs are increasing in incidence, possibly due to increasing engagement in risky sexual activities associated with oral HPV infection [47]. http://dx.doi.org/10.1016/j.oraloncology.2014.11.015 1368-8375/Ó 2014 Elsevier Ltd. All rights reserved.
However, while the vast majority of individuals engaging in sexual activity will acquire at least one HPV infection during their lifetime, most will spontaneously clear such infections without morbidity. The need then is to identify additional factors that promote carcinogenesis. The data gathered to date point to CT as a promising candidate co-factor in OP carcinogenesis. Research explicitly examining the possible roles of oral CT infection in OP carcinogenesis should be performed. Conflict of interest statement None declared. Acknowledgement There was no funding associated with this work. SS was funded by the Barnes-Jewish Hospital Foundation. References [1] Schiffman M, Castle PE, Jeronimo J, Rodriguez AC, Wacholder S. Human papillomavirus and cervical cancer. Lancet 2007;370:890–907. [2] Jayaprakash V, Reid M, Hatton E, Merzianu M, Rigual N, Marshall J, et al. Human papillomavirus types 16 and 18 in epithelial dysplasia of oral cavity and oropharynx: a meta-analysis, 1985–2010. Oral Oncol 2011;47:1048–54. [3] Zaravinos A. An updated overview of HPV-associated head and neck carcinomas. Oncotarget 2014;5:3956–69. [4] National Institutes of Health. National Cancer Institute. HPV and cancer. [accessed 15.10.2014]. [5] Silva J, Cerqueira F, Medeiros R. Chlamydia trachomatis infection: implications for HPV status and cervical cancer. Arch Gynecol Obstet 2014;289:715–23. [6] Bhatla N, Puri K, Joseph E, Kriplani A, Iyer VK, Sreenivas V. Association of Chlamydia trachomatis infection with human papillomavirus (HPV) & cervical intraepithelial neoplasia – a pilot study. Indian J Med Res 2013;137:533–9. [7] Smith JS, Bosetti C, Munoz N, Herrero R, Bosch FX, Eluf-Neto J, et al. Chlamydia trachomatis and invasive cervical cancer: a pooled analysis of the IARC multicentric case-control study. Int J Cancer J Int Cancer 2004;111:431–9. [8] Koutsky LA, Holmes KK, Critchlow CW, Stevens CE, Paavonen J, Beckmann AM, et al. A cohort study of the risk of cervical intraepithelial neoplasia grade 2 or 3 in relation to papillomavirus infection. New England J Med 1992;327:1272–8. [9] Anttila T, Saikku P, Koskela P, Bloigu A, Dillner J, Ikaheimo I, et al. Serotypes of Chlamydia trachomatis and risk for development of cervical squamous cell carcinoma. JAMA 2001;285:47–51. [10] Lehtinen M, Dillner J, Knekt P, Luostarinen T, Aromaa A, Kirnbauer R, et al. Serologically diagnosed infection with human papillomavirus type 16 and risk for subsequent development of cervical carcinoma: nested case-control study. BMJ (Clinical research ed) 1996;312:537–9. [11] Wallin KL, Wiklund F, Luostarinen T, Angstrom T, Anttila T, Bergman F, et al. A population-based prospective study of Chlamydia trachomatis infection and cervical carcinoma. Int J Cancer J Int Cancer 2002;101:371–4. [12] Madeleine MM, Anttila T, Schwartz SM, Saikku P, Leinonen M, Carter JJ, et al. Risk of cervical cancer associated with Chlamydia trachomatis antibodies by histology, HPV type and HPV cofactors. Int J Cancer J Int Cancer 2007;120: 650–5. [13] Naucler P, Chen HC, Persson K, You SL, Hsieh CY, Sun CA, et al. Seroprevalence of human papillomaviruses and Chlamydia trachomatis and cervical cancer risk: nested case-control study. J Gen Virol 2007;88:814–22.
Letter to the Editor / Oral Oncology 51 (2015) e8–e9 [14] Lehtinen M, Ault KA, Lyytikainen E, Dillner J, Garland SM, Ferris DG, et al. Chlamydia trachomatis infection and risk of cervical intraepithelial neoplasia. Sex Trans Infect 2011;87:372–6. [15] Ferrera A, Baay MF, Herbrink P, Figueroa M, Velema JP, Melchers WJ. A seroepidemiological study of the relationship between sexually transmitted agents and cervical cancer in Honduras. Int J Cancer J Int Cancer 1997;73:781–5. [16] Castle PE, Escoffery C, Schachter J, Rattray C, Schiffman M, Moncada J, et al. Chlamydia trachomatis, herpes simplex virus 2, and human T-cell lymphotrophic virus type 1 are not associated with grade of cervical neoplasia in Jamaican colposcopy patients. Sex Transm Dis 2003;30:575–80. [17] Safaeian M, Quint K, Schiffman M, Rodriguez AC, Wacholder S, Herrero R, et al. Chlamydia trachomatis and risk of prevalent and incident cervical premalignancy in a population-based cohort. J Natl Cancer Inst 2010;102: 1794–804. [18] Centers for disease control and prevention. Incidence, prevalence, and cost of sexually transmitted infections in the United States. [accessed 15.10.2014]. [19] World Health Organization. Global incidence and prevalence of selected curable sexually transmitted infections; 2008. [accessed 15.10.2014]. [20] Centers for Disease Control and Prevention. Human Papillomavirus (HPV). [accessed 16.10.2014]. [21] Chesson HW, Dunne EF, Hariri S, Markowitz LE. The estimated lifetime probability of acquiring human papillomavirus in the United States. Sex Transm Dis 2014;41:660–4. [22] Brown B, Blas MM, Cabral A, Carcamo C, Gravitt PE, Halsey N. Oral sex practices, oral human papillomavirus and correlations between oral and cervical human papillomavirus prevalence among female sex workers in Lima, Peru. Int J STD AIDS 2011;22:655–8. [23] Leichliter JS, Chandra A, Liddon N, Fenton KA, Aral SO. Prevalence and correlates of heterosexual anal and oral sex in adolescents and adults in the United States. J Infect Dis 2007;196:1852–9. [24] Marcus JL, Kohn RP, Barry PM, Philip SS, Bernstein KT. Chlamydia trachomatis and Neisseria gonorrhoeae transmission from the female oropharynx to the male urethra. Sex Transm Dis 2011;38:372–3. [25] Nakashima K, Shigehara K, Kawaguchi S, Wakatsuki A, Kobori Y, Nakashima K, et al. Prevalence of human papillomavirus infection in the oropharynx and urine among sexually active men: a comparative study of infection by papillomavirus and other organisms, including Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma spp., and Ureaplasma spp. BMC Infect Dis 2014;14:43. [26] Jenkins WD, Nessa LL, Clark T. Cross-sectional study of pharyngeal and genital chlamydia and gonorrhoea infections in emergency department patients. Sex Trans Infect 2014;90:246–9. [27] Karlsson A, Osterlund A, Forssen A. Pharyngeal Chlamydia trachomatis is not uncommon any more. Scand J Infect Dis 2011;43:344–8. [28] Antonsson A, Cornford M, Perry S, Davis M, Dunne MP, Whiteman DC. Prevalence and risk factors for oral HPV infection in young Australians. PLoS ONE 2014;9:e91761. [29] Gillison ML, Broutian T, Pickard RK, Tong ZY, Xiao W, Kahle L, et al. Prevalence of oral HPV infection in the United States, 2009–2010. JAMA 2012;307:693–703. [30] Panatto D, Amicizia D, Bianchi S, Frati ER, Zotti CM, Lai PL, et al. Chlamydia trachomatis prevalence and chlamydial/HPV co-infection among HPVunvaccinated young Italian females with normal cytology. Human Vaccines Immunother 2014;11. [31] Pereira SM, Etlinger D, Aguiar LS, Peres SV, Longatto Filho A. Simultaneous Chlamydia trachomatis and HPV infection in pregnant women. Diagn Cytopathol 2010;38:397–401. [32] Kessler M, Zielecki J, Thieck O, Mollenkopf HJ, Fotopoulou C, Meyer TF. Chlamydia trachomatis disturbs epithelial tissue homeostasis in fallopian tubes via paracrine Wnt signaling. Am J Pathol 2012;180:186–98.
e9
[33] Chumduri C, Gurumurthy RK, Zadora PK, Mi Y, Meyer TF. Chlamydia infection promotes host DNA damage and proliferation but impairs the DNA damage response. Cell Host Microbe 2013;13:746–58. [34] Kun D, Xiang-Lin C, Ming Z, Qi L. Chlamydia inhibit host cell apoptosis by inducing Bag-1 via the MAPK/ERK survival pathway. Apoptosis Int J Program Cell Death 2013;18:1083–92. [35] Fan T, Lu H, Hu H, Shi L, McClarty GA, Nance DM, et al. Inhibition of apoptosis in chlamydia-infected cells: blockade of mitochondrial cytochrome c release and caspase activation. J Exp Med 1998;187:487–96. [36] Williams VM, Filippova M, Soto U, Duerksen-Hughes PJ. HPV-DNA integration and carcinogenesis: putative roles for inflammation and oxidative stress. Future Virol 2011;6:45–57. [37] Shao R, Wang X, Wang W, Stener-Victorin E, Mallard C, Brannstrom M, et al. From mice to women and back again: causalities and clues for Chlamydiainduced tubal ectopic pregnancy. Fertil Steril 2012;98:1175–85. [38] Burd EM. Human papillomavirus and cervical cancer. Clin Microbiol Rev 2003;16:1–17. [39] Schleimer RP, Kato A, Kern R, Kuperman D, Avila PC. Epithelium: at the interface of innate and adaptive immune responses. J Allergy Clin Immunol 2007;120:1279–84. [40] Choroszy-Krol IC, Frej-Madrzak M, Jama-Kmiecik A, Bober T, Jolanta Sarowska J. Characteristics of the Chlamydia trachomatis species – immunopathology and infections. Adv Clin Exp Med Off Organ Wroclaw Med Univ 2012;21:99–808. [41] Mascellino MT, Boccia P, Oliva A. Immunopathogenesis in Chlamydia trachomatis Infected Women. ISRN Obstet Gynecol 2011;2011:436936. [42] Buchholz KR, Stephens RS. The extracellular signal-regulated kinase/mitogenactivated protein kinase pathway induces the inflammatory factor interleukin8 following Chlamydia trachomatis infection. Infect Immun 2007;75:5924–9. [43] Abdul-Sater AA, Said-Sadier N, Padilla EV, Ojcius DM. Chlamydial infection of monocytes stimulates IL-1beta secretion through activation of the NLRP3 inflammasome. Microbes Infect/Institut Pasteur 2010;12:652–61. [44] Zhou H, Huang Q, Li Z, Wu Y, Xie X, Ma K, et al. PORF5 plasmid protein of Chlamydia trachomatis induces MAPK-mediated pro-inflammatory cytokines via TLR2 activation in THP-1 cells. Sci China Life Sci 2013;56:460–6. [45] Coussens LM, Werb Z. Inflammation and cancer. Nature 2002;420:860–7. [46] Tili E, Michaille JJ, Wernicke D, Alder H, Costinean S, Volinia S, et al. Mutator activity induced by microRNA-155 (miR-155) links inflammation and cancer. Proc Natl Acad Sci USA 2011;108:4908–13. [47] Kreimer AR, Alberg AJ, Daniel R, Gravitt PE, Viscidi R, Garrett ES, et al. Oral human papillomavirus infection in adults is associated with sexual behavior and HIV serostatus. J Infect Dis 2004;189:686–98.
⇑
Wiley D. Jenkins Population Health Science Program, Center for Clinical Research, Simmons Cancer Institute, Southern Illinois University School of Medicine, 801 N. Rutledge St., Springfield, IL 62794-9664, United States ⇑ Tel.: +1 217 545 8717. E-mail address: [email protected] Kelsey LeVault Population Health Science Program, Center for Clinical Research, Southern Illinois University School of Medicine, 801 N. Rutledge St., Springfield, IL 62794-9664, United States Siobhan Sutcliffe Division of Public Health Sciences and The Alvin J. Siteman Cancer Center, Department of Surgery, Washington University School of Medicine, 660 S. Euclid Ave., Rm. 2-208S, Box 8100, St. Louis, MO 63110, United States Available online 12 December 2014
Contents lists available at ScienceDirect
Oral Oncology journal homepage: www.elsevier.com/locate/oraloncology
Letter to the Editor Chlamydia trachomatis infection: Possible cofactor for oropharyngeal cancer development?
The preponderance of evidence shows that nearly all cervical cancers and many oropharyngeal cancers (OPCs) are due to human papillomavirus (HPV) infection [1–3]. However, only a small proportion of women infected with HPV, even high risk variants such as 16 and 18, progress to invasive cancer [4]. Chlamydia trachomatis (CT) co-infection is believed to be a possible co-factor that tips the balance from infection to oncogenesis [5,6]. Positive associations have been observed between CT infection and squamous cell carcinoma of the cervix or its precursor lesions in most [7–14], but not all [15–17], previous epidemiologic studies that controlled for HPV infection. By analogy, we propose that CT infection may also be a cofactor for HPV-associated OPCs. CT has been extensively studied as a sexually transmitted infection (STI), most often associated with genital and anal sites of infection. In both the US and globally, CT is the most common bacterial STI with an estimated 2,860,000 and 105,700,000 cases, respectively, in 2008 [18,19]. HPV (all variants) is the most common STI with an estimated 79 million Americans currently infected, and lifetime risks of HPV acquisition for those with at least one opposite-sex partner of 84.6% for females and 91.3% for males [20,21]. There is considerable opportunity for oral infection, as while approximately three quarters of US individuals engage in oral sex, condoms are used only 6–10% of the time and oral infection prevalences range from 1.5–12% (CT) and from 2.3–7.6% (HPV) [22–29]. Given that both CT and HPV are obligate intracellular organisms, prefer similar tissues, and are both transmitted via sexual contact, it is not surprising that they may co-occur within a single individual [6,30,31]. Chlamydial infection may contribute to carcinogenesis by its possible impact upon host cell structure, gene regulation and maintenance. Infected cells experience substantial epithelial disruption, increased and unrepaired DNA double-strand breaks due to CT-induced reactive oxygen species, increased oncogenic signaling, continued proliferation, and inhibition of apoptosis [32–36]. The main tissue targets of both chlamydia and HPV are the epithelial cells lining mucosal surfaces, and such tissues are important mediators of organism immune response [37–39]. Chlamydia infection may lead to chronic persistent inflammation, itself associated with rapid cell division, debilitated DNA repair, oxidative stress, increased levels of prostaglandins and cytokines, inflammatory pathway stimulation/upregulation, and oncogenesis [40–45]. As infection-driven inflammation has been implicated in 15–20% of cancers, these data support the hypothesis that chlamydial infection may contribute to oncogenesis [46]. Epidemiological data show that HPV-associated OPCs are increasing in incidence, possibly due to increasing engagement in risky sexual activities associated with oral HPV infection [47]. http://dx.doi.org/10.1016/j.oraloncology.2014.11.015 1368-8375/Ó 2014 Elsevier Ltd. All rights reserved.
However, while the vast majority of individuals engaging in sexual activity will acquire at least one HPV infection during their lifetime, most will spontaneously clear such infections without morbidity. The need then is to identify additional factors that promote carcinogenesis. The data gathered to date point to CT as a promising candidate co-factor in OP carcinogenesis. Research explicitly examining the possible roles of oral CT infection in OP carcinogenesis should be performed. Conflict of interest statement None declared. Acknowledgement There was no funding associated with this work. SS was funded by the Barnes-Jewish Hospital Foundation. References [1] Schiffman M, Castle PE, Jeronimo J, Rodriguez AC, Wacholder S. Human papillomavirus and cervical cancer. Lancet 2007;370:890–907. [2] Jayaprakash V, Reid M, Hatton E, Merzianu M, Rigual N, Marshall J, et al. Human papillomavirus types 16 and 18 in epithelial dysplasia of oral cavity and oropharynx: a meta-analysis, 1985–2010. Oral Oncol 2011;47:1048–54. [3] Zaravinos A. An updated overview of HPV-associated head and neck carcinomas. Oncotarget 2014;5:3956–69. [4] National Institutes of Health. National Cancer Institute. HPV and cancer. [accessed 15.10.2014]. [5] Silva J, Cerqueira F, Medeiros R. Chlamydia trachomatis infection: implications for HPV status and cervical cancer. Arch Gynecol Obstet 2014;289:715–23. [6] Bhatla N, Puri K, Joseph E, Kriplani A, Iyer VK, Sreenivas V. Association of Chlamydia trachomatis infection with human papillomavirus (HPV) & cervical intraepithelial neoplasia – a pilot study. Indian J Med Res 2013;137:533–9. [7] Smith JS, Bosetti C, Munoz N, Herrero R, Bosch FX, Eluf-Neto J, et al. Chlamydia trachomatis and invasive cervical cancer: a pooled analysis of the IARC multicentric case-control study. Int J Cancer J Int Cancer 2004;111:431–9. [8] Koutsky LA, Holmes KK, Critchlow CW, Stevens CE, Paavonen J, Beckmann AM, et al. A cohort study of the risk of cervical intraepithelial neoplasia grade 2 or 3 in relation to papillomavirus infection. New England J Med 1992;327:1272–8. [9] Anttila T, Saikku P, Koskela P, Bloigu A, Dillner J, Ikaheimo I, et al. Serotypes of Chlamydia trachomatis and risk for development of cervical squamous cell carcinoma. JAMA 2001;285:47–51. [10] Lehtinen M, Dillner J, Knekt P, Luostarinen T, Aromaa A, Kirnbauer R, et al. Serologically diagnosed infection with human papillomavirus type 16 and risk for subsequent development of cervical carcinoma: nested case-control study. BMJ (Clinical research ed) 1996;312:537–9. [11] Wallin KL, Wiklund F, Luostarinen T, Angstrom T, Anttila T, Bergman F, et al. A population-based prospective study of Chlamydia trachomatis infection and cervical carcinoma. Int J Cancer J Int Cancer 2002;101:371–4. [12] Madeleine MM, Anttila T, Schwartz SM, Saikku P, Leinonen M, Carter JJ, et al. Risk of cervical cancer associated with Chlamydia trachomatis antibodies by histology, HPV type and HPV cofactors. Int J Cancer J Int Cancer 2007;120: 650–5. [13] Naucler P, Chen HC, Persson K, You SL, Hsieh CY, Sun CA, et al. Seroprevalence of human papillomaviruses and Chlamydia trachomatis and cervical cancer risk: nested case-control study. J Gen Virol 2007;88:814–22.
Letter to the Editor / Oral Oncology 51 (2015) e8–e9 [14] Lehtinen M, Ault KA, Lyytikainen E, Dillner J, Garland SM, Ferris DG, et al. Chlamydia trachomatis infection and risk of cervical intraepithelial neoplasia. Sex Trans Infect 2011;87:372–6. [15] Ferrera A, Baay MF, Herbrink P, Figueroa M, Velema JP, Melchers WJ. A seroepidemiological study of the relationship between sexually transmitted agents and cervical cancer in Honduras. Int J Cancer J Int Cancer 1997;73:781–5. [16] Castle PE, Escoffery C, Schachter J, Rattray C, Schiffman M, Moncada J, et al. Chlamydia trachomatis, herpes simplex virus 2, and human T-cell lymphotrophic virus type 1 are not associated with grade of cervical neoplasia in Jamaican colposcopy patients. Sex Transm Dis 2003;30:575–80. [17] Safaeian M, Quint K, Schiffman M, Rodriguez AC, Wacholder S, Herrero R, et al. Chlamydia trachomatis and risk of prevalent and incident cervical premalignancy in a population-based cohort. J Natl Cancer Inst 2010;102: 1794–804. [18] Centers for disease control and prevention. Incidence, prevalence, and cost of sexually transmitted infections in the United States. [accessed 15.10.2014]. [19] World Health Organization. Global incidence and prevalence of selected curable sexually transmitted infections; 2008. [accessed 15.10.2014]. [20] Centers for Disease Control and Prevention. Human Papillomavirus (HPV). [accessed 16.10.2014]. [21] Chesson HW, Dunne EF, Hariri S, Markowitz LE. The estimated lifetime probability of acquiring human papillomavirus in the United States. Sex Transm Dis 2014;41:660–4. [22] Brown B, Blas MM, Cabral A, Carcamo C, Gravitt PE, Halsey N. Oral sex practices, oral human papillomavirus and correlations between oral and cervical human papillomavirus prevalence among female sex workers in Lima, Peru. Int J STD AIDS 2011;22:655–8. [23] Leichliter JS, Chandra A, Liddon N, Fenton KA, Aral SO. Prevalence and correlates of heterosexual anal and oral sex in adolescents and adults in the United States. J Infect Dis 2007;196:1852–9. [24] Marcus JL, Kohn RP, Barry PM, Philip SS, Bernstein KT. Chlamydia trachomatis and Neisseria gonorrhoeae transmission from the female oropharynx to the male urethra. Sex Transm Dis 2011;38:372–3. [25] Nakashima K, Shigehara K, Kawaguchi S, Wakatsuki A, Kobori Y, Nakashima K, et al. Prevalence of human papillomavirus infection in the oropharynx and urine among sexually active men: a comparative study of infection by papillomavirus and other organisms, including Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma spp., and Ureaplasma spp. BMC Infect Dis 2014;14:43. [26] Jenkins WD, Nessa LL, Clark T. Cross-sectional study of pharyngeal and genital chlamydia and gonorrhoea infections in emergency department patients. Sex Trans Infect 2014;90:246–9. [27] Karlsson A, Osterlund A, Forssen A. Pharyngeal Chlamydia trachomatis is not uncommon any more. Scand J Infect Dis 2011;43:344–8. [28] Antonsson A, Cornford M, Perry S, Davis M, Dunne MP, Whiteman DC. Prevalence and risk factors for oral HPV infection in young Australians. PLoS ONE 2014;9:e91761. [29] Gillison ML, Broutian T, Pickard RK, Tong ZY, Xiao W, Kahle L, et al. Prevalence of oral HPV infection in the United States, 2009–2010. JAMA 2012;307:693–703. [30] Panatto D, Amicizia D, Bianchi S, Frati ER, Zotti CM, Lai PL, et al. Chlamydia trachomatis prevalence and chlamydial/HPV co-infection among HPVunvaccinated young Italian females with normal cytology. Human Vaccines Immunother 2014;11. [31] Pereira SM, Etlinger D, Aguiar LS, Peres SV, Longatto Filho A. Simultaneous Chlamydia trachomatis and HPV infection in pregnant women. Diagn Cytopathol 2010;38:397–401. [32] Kessler M, Zielecki J, Thieck O, Mollenkopf HJ, Fotopoulou C, Meyer TF. Chlamydia trachomatis disturbs epithelial tissue homeostasis in fallopian tubes via paracrine Wnt signaling. Am J Pathol 2012;180:186–98.
e9
[33] Chumduri C, Gurumurthy RK, Zadora PK, Mi Y, Meyer TF. Chlamydia infection promotes host DNA damage and proliferation but impairs the DNA damage response. Cell Host Microbe 2013;13:746–58. [34] Kun D, Xiang-Lin C, Ming Z, Qi L. Chlamydia inhibit host cell apoptosis by inducing Bag-1 via the MAPK/ERK survival pathway. Apoptosis Int J Program Cell Death 2013;18:1083–92. [35] Fan T, Lu H, Hu H, Shi L, McClarty GA, Nance DM, et al. Inhibition of apoptosis in chlamydia-infected cells: blockade of mitochondrial cytochrome c release and caspase activation. J Exp Med 1998;187:487–96. [36] Williams VM, Filippova M, Soto U, Duerksen-Hughes PJ. HPV-DNA integration and carcinogenesis: putative roles for inflammation and oxidative stress. Future Virol 2011;6:45–57. [37] Shao R, Wang X, Wang W, Stener-Victorin E, Mallard C, Brannstrom M, et al. From mice to women and back again: causalities and clues for Chlamydiainduced tubal ectopic pregnancy. Fertil Steril 2012;98:1175–85. [38] Burd EM. Human papillomavirus and cervical cancer. Clin Microbiol Rev 2003;16:1–17. [39] Schleimer RP, Kato A, Kern R, Kuperman D, Avila PC. Epithelium: at the interface of innate and adaptive immune responses. J Allergy Clin Immunol 2007;120:1279–84. [40] Choroszy-Krol IC, Frej-Madrzak M, Jama-Kmiecik A, Bober T, Jolanta Sarowska J. Characteristics of the Chlamydia trachomatis species – immunopathology and infections. Adv Clin Exp Med Off Organ Wroclaw Med Univ 2012;21:99–808. [41] Mascellino MT, Boccia P, Oliva A. Immunopathogenesis in Chlamydia trachomatis Infected Women. ISRN Obstet Gynecol 2011;2011:436936. [42] Buchholz KR, Stephens RS. The extracellular signal-regulated kinase/mitogenactivated protein kinase pathway induces the inflammatory factor interleukin8 following Chlamydia trachomatis infection. Infect Immun 2007;75:5924–9. [43] Abdul-Sater AA, Said-Sadier N, Padilla EV, Ojcius DM. Chlamydial infection of monocytes stimulates IL-1beta secretion through activation of the NLRP3 inflammasome. Microbes Infect/Institut Pasteur 2010;12:652–61. [44] Zhou H, Huang Q, Li Z, Wu Y, Xie X, Ma K, et al. PORF5 plasmid protein of Chlamydia trachomatis induces MAPK-mediated pro-inflammatory cytokines via TLR2 activation in THP-1 cells. Sci China Life Sci 2013;56:460–6. [45] Coussens LM, Werb Z. Inflammation and cancer. Nature 2002;420:860–7. [46] Tili E, Michaille JJ, Wernicke D, Alder H, Costinean S, Volinia S, et al. Mutator activity induced by microRNA-155 (miR-155) links inflammation and cancer. Proc Natl Acad Sci USA 2011;108:4908–13. [47] Kreimer AR, Alberg AJ, Daniel R, Gravitt PE, Viscidi R, Garrett ES, et al. Oral human papillomavirus infection in adults is associated with sexual behavior and HIV serostatus. J Infect Dis 2004;189:686–98.
⇑
Wiley D. Jenkins Population Health Science Program, Center for Clinical Research, Simmons Cancer Institute, Southern Illinois University School of Medicine, 801 N. Rutledge St., Springfield, IL 62794-9664, United States ⇑ Tel.: +1 217 545 8717. E-mail address: [email protected] Kelsey LeVault Population Health Science Program, Center for Clinical Research, Southern Illinois University School of Medicine, 801 N. Rutledge St., Springfield, IL 62794-9664, United States Siobhan Sutcliffe Division of Public Health Sciences and The Alvin J. Siteman Cancer Center, Department of Surgery, Washington University School of Medicine, 660 S. Euclid Ave., Rm. 2-208S, Box 8100, St. Louis, MO 63110, United States Available online 12 December 2014
