Chlamydia Infection as a Risk Factor for Cervical Cancer: A Systematic Review and Meta-Analysis
-
Anaanthan Bhuvanendran Pillai
,
Chin Mun Wong
,
Noor Dalila Inche Zainal Abidin
,
Sharifah Fazlinda Syed Nor
,
Mohd Fathulzhafran Mohd Hanan
,
Siti Rasidah Abd Ghani
,
Nurul Afzan Aminuddin
,
Nazarudin Safian
Abstract
Background: We reviewed studies on the prevalence of Chlamydia infection as a risk factor for developing cervical cancer in a meta-analysis studies published in that subject area.
Methods: Cochrane Library and PubMed databases were systematically searched for articles (observational and randomized controlled trials) published from 2008-2018. A meta-analysis of studies was performed to analyse the association between chlamydia infection and cervical cancer.
Results: Five articles were included in the final analysis (N=5271). All five articles were case-control studies, of which three studies sampled from population-based registries. All studies involved with sexually active women with minimum 15 years old. Three studies reported the association of C. trachomatis infection cervical cancers, two other studies reported C. trachomatis-HPV co-infection in association with cervical cancer. Result showed C. trachomatis has an overall prevalence of 31.9%, pooled OR 1.96, 95% CI 1.05 to 3.67, OR 2.13, 95% CI 1.78 to 2.54 among cervical cancer. There was a mild publication bias detected at 3.0 effect estimation. Heterogeneity detected from clinical and methodological diversities particularly from C. trachomatis-HPV co-infection subgroup analysis, including sampling bias, geographical strain diversity, and different outcome endpoint measured.
Conclusion: C. trachomatis infection was significantly associated with the development of cervical cancer. Co-infection of C. trachomatis-HPV with cervical cancer is plausibly sound but temporality of C. trachomatis-HPV with the development of cervical cancer need to be proven in future prospective cohort studies.
1. World Health Organization (2018). Cervical cancer.World Health Organization. http://www.who.int/cancer/prevention/diagnosis-screening/cervical-cancer/en/ (accessed September 2018).
2. Azizah AM, Nor Saleha I.T, Noor Hashimah A et al (2018). Malaysian national cancer registry report 2007-2011. Putrajaya: National Cancer Institute, Ministry of Health Malaysia; 2015. 228p.https://www.crc.gov.my/wp-content/uploads/documents/report/MNCRRrepor2007-2011.pdf
3. Lehtinen M, Ault KA, Lyytikainen E, et al (2011). Chlamydia trachomatis infection and risk of cervical intraepithelial neoplasia. Sex Transm Infect, 87(5):372-6.
4. Doll R, Peto R (1981). The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. J Natl Cancer Inst, 66(6):1191-308.
5. Bosch FX, Castellsagué X, Muñoz N, et al (1996). Male sexual behavior and human papillomavirus DNA: key risk factors for cervical cancer in Spain. J Natl Cancer Inst, 88(15):1060-7.
6. Koskela P, Anttila T, Bjørge T, et al (2000). Chlamydia trachomatis infection as a risk factor for invasive cervical cancer. Int J Cancer, 85(1):35-9.
7. Stang A (2010). Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 25(9):603-605.
8. RevMan C (2014). Review manager (revman)[computer program]. Version 5.3. The Nordic Cochrane Centre, The Cochrane Collaboration Copenhagen.
9. DerSimonian R, Laird N (1986). Meta-analysis in clinical trials. Control Clin Trials, 7 (3):177-88.
10. Cochran, William G (1954). The combination of estimates from different experiments. Biometrics, 10(1):101-29.
11. Tungsrithong N, Kasinpila C, Maneenin C, et al (2014). Lack of significant effects of Chlamydia trachomatis infection on cervical cancer risk in a nested case-control study in North-East Thailand. Asian Pac J Cancer Prev, 15(3):1497-500.
12. Calil LN, Igansi CN, Meurer L, et al (2011). Chlamydia trachomatis and human papillomavirus coinfection: association with p16INK4a and Ki67 expression in biopsies of patients with pre-neoplastic and neoplastic lesions. Braz J Infect Dis, 15(2):126-31.
13. Chumduri C, Gurumurthy RK, Zadora PK, et al (2013). Chlamydia infection promotes host DNA damage and proliferation but impairs the DNA damage response. Cell Host Microbe, 13(6):746-58.
14. Onel M, Küçücük S, Töre G, et al (2013). Investigation of Chlamydia trachomatis seropositivity in patients with cervical cancer. Mikrobiyol Bul, 47(4):702-7.
15. Farivar TN, Johari P (2012). Lack of association between Chlamydia trachomatis infection and cervical cancer-Taq Man realtime PCR assay findings. Asian Pac J Cancer Prev, 13(8):3701-4.
16. Smelov V, Gheit T, Sundström K, et al (2016). Lack of significant effects of chlamydia trachomatis infection on cervical adenocarcinoma risk: nested case-control study. PLoS One, 11(5):e0156215.
17. Safaeian M, Quint K, Schiffman M, et al (2010). Chlamydia trachomatis and risk of prevalent and incident cervical premalignancy in a population-based cohort. J Natl Cancer Inst, 102(23):1794-804.
18. Castellsague X, Pawlita M, Roura E, et al (2014). Prospective seroepidemiologic study on the role of Human Papillomavirus and other infections in cervical carcinogenesis: evidence from the EPIC cohort. Int J Cancer, 135(2):440-52.
19. Dahlström LA, Andersson K, Luostarinen T, et al (2011). Prospective seroepidemiologic study of human papillomavirus and other risk factors in cervical cancer. Cancer Epidemiol Biomarkers Prev, 20(12):2541-50.
20. Zhu H, Shen Z, Luo H,et al (2016). Chlamydia trachomatis infection-associated risk of cervical cancer: a meta-analysis. Medicine (Baltimore), 95(13):e3077.
21. Silins I, Ryd W, Strand A, et al (2005). Chlamydia trachomatis infection and persistence of human papillomavirus. Int J Cancer, 116(1):110-5.
22. Bhatla N, Puri K, Joseph E, et al (2013). Association of Chlamydia trachomatis infection with human papillomavirus (HPV) & cervical intraepithelial neoplasia-a pilot study. Indian J Med Res, 137(3):533-9.
23. Samoff E, Koumans EH, Markowitz LE, et al (2005). Association of Chlamydia trachomatis with persistence of high-risk types of human papillomavirus in a cohort of female adolescents. Am J Epidemiol, 162(7):668-75.
24. Wohlmeister D, Vianna DR, Helfer VE, et al (2016). Association of human papillomavirus and Chlamydia trachomatis with intraepithelial alterations in cervix samples. Mem Inst Oswaldo Cruz,
111(2):106-13.
25. Luostarinen T, Namujju PB, Merikukka M, et al (2013). Order of HPV/Chlamydia infections and cervical high‐grade precancer risk: A case-cohort study. Int J Cancer, 133(7):1756-9.
26. Karim S, Souho T, Benlemlih M, et al (2018). Cervical cancer induction enhancement potential of Chlamydia trachomatis: a systematic review. Curr Microbiol, 75(12):1667-74.
27. Munoz N, Kato I, Bosch FX, et al (1996). Risk factors for HPV DNA detection in middle-aged women. Sex Transm Dis, 23(6):504-10.
28. Seraceni S, De Seta F, Colli C, et al (2014). High prevalence of hpv multiple genotypes in women with
persistent chlamydia trachomatis infection. Infect Agent Cancer, 9:30.
29. de Abreu AL, Nogara PR, Souza RP, et al (2012). Molecular detection of HPV and Chlamydia trachomatis infections in Brazilian women with abnormal cervical cytology. American J Trop Med Hyg, 87(6):1149-51.
30. Vriend HJ, Bogaards JA, van Bergen JE, et al (2015). Medical Microbiological Laboratories and the CSI group. Incidence and persistence of carcinogenic genital human papillomavirus infections in young women with or without Chlamydia trachomatis co‐infection. Cancer Med, 4(10):1589-98.
31. Madeleine MM, Anttila T, Schwartz SM, et al (2007). Risk of cervical cancer associated with Chlamydia trachomatis antibodies by histology, HPV type and HPV cofactors. Int J Cancer, 120(3):650-5.
32. Gurumurthy RK, Mäurer AP, Machuy N, et al (2010). A loss-of-function screen reveals Ras-and Raf-independent MEK-ERK signaling during Chlamydia trachomatis infection. Sci Signal, 3(113):ra21.
33. Kun D, Xiang-Lin C, Ming Z, et al (2013). Chlamydia inhibit host cell apoptosis by inducing Bag-1 via the MAPK/ERK survival pathway. Apoptosis, 18(9):1083-92.
34. Silva J, Cerqueira F, Medeiros R (2014). Chlamydia trachomatis infection: implications for HPV status and cervical cancer. Arch Gynecol Obstet, 289(4):715-23.
35. Fischer N (2002). Chlamydia trachomatis infection in cervical intraepithelial neoplasia and invasive carcinoma. Eur J Gynaecol Oncol, 23(3):247-50.
2. Azizah AM, Nor Saleha I.T, Noor Hashimah A et al (2018). Malaysian national cancer registry report 2007-2011. Putrajaya: National Cancer Institute, Ministry of Health Malaysia; 2015. 228p.https://www.crc.gov.my/wp-content/uploads/documents/report/MNCRRrepor2007-2011.pdf
3. Lehtinen M, Ault KA, Lyytikainen E, et al (2011). Chlamydia trachomatis infection and risk of cervical intraepithelial neoplasia. Sex Transm Infect, 87(5):372-6.
4. Doll R, Peto R (1981). The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. J Natl Cancer Inst, 66(6):1191-308.
5. Bosch FX, Castellsagué X, Muñoz N, et al (1996). Male sexual behavior and human papillomavirus DNA: key risk factors for cervical cancer in Spain. J Natl Cancer Inst, 88(15):1060-7.
6. Koskela P, Anttila T, Bjørge T, et al (2000). Chlamydia trachomatis infection as a risk factor for invasive cervical cancer. Int J Cancer, 85(1):35-9.
7. Stang A (2010). Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 25(9):603-605.
8. RevMan C (2014). Review manager (revman)[computer program]. Version 5.3. The Nordic Cochrane Centre, The Cochrane Collaboration Copenhagen.
9. DerSimonian R, Laird N (1986). Meta-analysis in clinical trials. Control Clin Trials, 7 (3):177-88.
10. Cochran, William G (1954). The combination of estimates from different experiments. Biometrics, 10(1):101-29.
11. Tungsrithong N, Kasinpila C, Maneenin C, et al (2014). Lack of significant effects of Chlamydia trachomatis infection on cervical cancer risk in a nested case-control study in North-East Thailand. Asian Pac J Cancer Prev, 15(3):1497-500.
12. Calil LN, Igansi CN, Meurer L, et al (2011). Chlamydia trachomatis and human papillomavirus coinfection: association with p16INK4a and Ki67 expression in biopsies of patients with pre-neoplastic and neoplastic lesions. Braz J Infect Dis, 15(2):126-31.
13. Chumduri C, Gurumurthy RK, Zadora PK, et al (2013). Chlamydia infection promotes host DNA damage and proliferation but impairs the DNA damage response. Cell Host Microbe, 13(6):746-58.
14. Onel M, Küçücük S, Töre G, et al (2013). Investigation of Chlamydia trachomatis seropositivity in patients with cervical cancer. Mikrobiyol Bul, 47(4):702-7.
15. Farivar TN, Johari P (2012). Lack of association between Chlamydia trachomatis infection and cervical cancer-Taq Man realtime PCR assay findings. Asian Pac J Cancer Prev, 13(8):3701-4.
16. Smelov V, Gheit T, Sundström K, et al (2016). Lack of significant effects of chlamydia trachomatis infection on cervical adenocarcinoma risk: nested case-control study. PLoS One, 11(5):e0156215.
17. Safaeian M, Quint K, Schiffman M, et al (2010). Chlamydia trachomatis and risk of prevalent and incident cervical premalignancy in a population-based cohort. J Natl Cancer Inst, 102(23):1794-804.
18. Castellsague X, Pawlita M, Roura E, et al (2014). Prospective seroepidemiologic study on the role of Human Papillomavirus and other infections in cervical carcinogenesis: evidence from the EPIC cohort. Int J Cancer, 135(2):440-52.
19. Dahlström LA, Andersson K, Luostarinen T, et al (2011). Prospective seroepidemiologic study of human papillomavirus and other risk factors in cervical cancer. Cancer Epidemiol Biomarkers Prev, 20(12):2541-50.
20. Zhu H, Shen Z, Luo H,et al (2016). Chlamydia trachomatis infection-associated risk of cervical cancer: a meta-analysis. Medicine (Baltimore), 95(13):e3077.
21. Silins I, Ryd W, Strand A, et al (2005). Chlamydia trachomatis infection and persistence of human papillomavirus. Int J Cancer, 116(1):110-5.
22. Bhatla N, Puri K, Joseph E, et al (2013). Association of Chlamydia trachomatis infection with human papillomavirus (HPV) & cervical intraepithelial neoplasia-a pilot study. Indian J Med Res, 137(3):533-9.
23. Samoff E, Koumans EH, Markowitz LE, et al (2005). Association of Chlamydia trachomatis with persistence of high-risk types of human papillomavirus in a cohort of female adolescents. Am J Epidemiol, 162(7):668-75.
24. Wohlmeister D, Vianna DR, Helfer VE, et al (2016). Association of human papillomavirus and Chlamydia trachomatis with intraepithelial alterations in cervix samples. Mem Inst Oswaldo Cruz,
111(2):106-13.
25. Luostarinen T, Namujju PB, Merikukka M, et al (2013). Order of HPV/Chlamydia infections and cervical high‐grade precancer risk: A case-cohort study. Int J Cancer, 133(7):1756-9.
26. Karim S, Souho T, Benlemlih M, et al (2018). Cervical cancer induction enhancement potential of Chlamydia trachomatis: a systematic review. Curr Microbiol, 75(12):1667-74.
27. Munoz N, Kato I, Bosch FX, et al (1996). Risk factors for HPV DNA detection in middle-aged women. Sex Transm Dis, 23(6):504-10.
28. Seraceni S, De Seta F, Colli C, et al (2014). High prevalence of hpv multiple genotypes in women with
persistent chlamydia trachomatis infection. Infect Agent Cancer, 9:30.
29. de Abreu AL, Nogara PR, Souza RP, et al (2012). Molecular detection of HPV and Chlamydia trachomatis infections in Brazilian women with abnormal cervical cytology. American J Trop Med Hyg, 87(6):1149-51.
30. Vriend HJ, Bogaards JA, van Bergen JE, et al (2015). Medical Microbiological Laboratories and the CSI group. Incidence and persistence of carcinogenic genital human papillomavirus infections in young women with or without Chlamydia trachomatis co‐infection. Cancer Med, 4(10):1589-98.
31. Madeleine MM, Anttila T, Schwartz SM, et al (2007). Risk of cervical cancer associated with Chlamydia trachomatis antibodies by histology, HPV type and HPV cofactors. Int J Cancer, 120(3):650-5.
32. Gurumurthy RK, Mäurer AP, Machuy N, et al (2010). A loss-of-function screen reveals Ras-and Raf-independent MEK-ERK signaling during Chlamydia trachomatis infection. Sci Signal, 3(113):ra21.
33. Kun D, Xiang-Lin C, Ming Z, et al (2013). Chlamydia inhibit host cell apoptosis by inducing Bag-1 via the MAPK/ERK survival pathway. Apoptosis, 18(9):1083-92.
34. Silva J, Cerqueira F, Medeiros R (2014). Chlamydia trachomatis infection: implications for HPV status and cervical cancer. Arch Gynecol Obstet, 289(4):715-23.
35. Fischer N (2002). Chlamydia trachomatis infection in cervical intraepithelial neoplasia and invasive carcinoma. Eur J Gynaecol Oncol, 23(3):247-50.
| Files | ||
| Issue | Vol 51 No 3 (2022) | |
| Section | Review Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v51i3.8926 | |
| Keywords | ||
| Chlamydia infection Human papilloma virus Sexually Transmitted disease Cervical carcinoma | ||
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How to Cite
1.
Bhuvanendran Pillai A, Wong CM, Inche Zainal Abidin ND, Syed Nor SF, Mohd Hanan MF, Abd Ghani SR, Aminuddin NA, Safian N. Chlamydia Infection as a Risk Factor for Cervical Cancer: A Systematic Review and Meta-Analysis. Iran J Public Health. 2022;51(3):508-517.
