CC BY 4.0 · Rev Bras Ginecol Obstet 2018; 40(09): 540-546
DOI: 10.1055/s-0038-1669994
Original Article
Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil

Sexually Transmitted Infections Detected by Multiplex Real Time PCR in Asymptomatic Women and Association with Cervical Intraepithelial Neoplasia

Infecções sexualmente transmissíveis detectadas por PCR multiplex em tempo real em mulheres assintomáticas e associação com neoplasia intraepitelial cervical
Luiza de Miranda Lima
1   Instituto de Educação e Pesquisa da Santa Casa, Belo Horizonte, MG, Brazil
,
Carolina René Hoelzle
1   Instituto de Educação e Pesquisa da Santa Casa, Belo Horizonte, MG, Brazil
,
Renata Toscano Simões
1   Instituto de Educação e Pesquisa da Santa Casa, Belo Horizonte, MG, Brazil
,
Maria Inês de Miranda Lima
1   Instituto de Educação e Pesquisa da Santa Casa, Belo Horizonte, MG, Brazil
,
Jordana Rodrigues Barbosa Fradico
2   Research and Development Division, Grupo Hermes Pardini, Vespasiano, MG, Brazil
,
Elvis Cristian Cueva Mateo
2   Research and Development Division, Grupo Hermes Pardini, Vespasiano, MG, Brazil
,
Danielle Alves Gomes Zauli
2   Research and Development Division, Grupo Hermes Pardini, Vespasiano, MG, Brazil
,
Victor Hugo Melo
3   Faculty of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
› Author Affiliations
Further Information

Publication History

20 March 2018

13 June 2018

Publication Date:
19 September 2018 (online)

Abstract

Objective To determine the frequency of sexually transmitted infections (STIs) in asymptomatic women and the association of STIs with cervical intraepithelial neoplasia (CIN).

Methods A cross-sectional study was performed, enrolling women examined in a general gynecology clinic and in a colposcopy referral center from October 2014 to October 2015. The colposcopy group consisted of 71 women, and the general gynecology group consisted of 55 women. Cervical samples were collected for cervical cytology and a multiplex real-time polymerase chain reaction (PCR) was developed to detect human papillomavirus (HPV) and the STIs caused by the following microorganisms: Chlamydia trachomatis, Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma urealyticum, and Neisseria gonorrhoeae. A multivariate analysis was performed by logistic regression, considering the significance level of 0.05.

Results The general frequency of STIs was: 46.8% (HPV); 27.8% (C. trachomatis); 28.6% (M. genitalium); 0.8% (M. hominis); 4.8% (U. urealyticum); and 4.8% (N. gonorrhoeae). The significant risk factors for CIN were: HPV infection (odds ratio [OR] = 2.53; p = 0.024); C. trachomatis (OR = 3.04; p = 0.009); M. genitalium (OR = 2.37; p = 0.04); and HPV and C. trachomatis coinfection (OR = 3.11; p = 0.023). After the multivariate analysis, a significant association was found between HPV and CIN (OR = 2.48; 95% confidence interval [95%CI]: 1.04–5.92; p = 0.04); and between C. trachomatis and CIN (OR = 2.69; 95%CI: 1.11–6.53; p = 0.028).

Conclusion The frequency of STIs was high in asymptomatic patients. Infections by HPV and C. trachomatis were independently associated with the presence of CIN. The high frequency of STIs in asymptomatic women suggests the need for routine screening of these infections.

Resumo

Objetivo Determinar a frequência de infecções sexualmente transmissíveis (ISTs) em mulheres assintomáticas e a associação destas infecções com a neoplasia intraepitelial cervical (NIC).

Métodos Foi realizado um estudo transversal recrutando mulheres atendidas em uma clínica ginecológica geral e em um centro de referência para colposcopia, de outubro de 2014 a outubro de 2015. O grupo de colposcopia consistiu de 71 mulheres, e o grupo de ginecologia geral consistiu de 55 mulheres. Amostras cervicais foram coletadas para citologia cervical e uma reação em cadeia de polimerase (RCP) multiplex em tempo real para detecção do vírus do papiloma humano (HPV) e das ISTs provocadas pelos seguintes micro-organismos: Chlamydia trachomatis, Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma urealyticum e Neisseria gonorrhoeae. Foi realizada uma análise multivariada por regressão logística, considerando-se o nível de significância de 0,05.

Resultados A frequência geral de ISTs foi: 46,8% (HPV); 27,8% (C. trachomatis); 28,6% (M. genitalium); 0,8% (M. hominis); 4,8% (U. urealyticum); e 4,8% (N. gonorrhoeae). Os fatores de risco significantes para NIC foram: infecção pelo HPV (razão de probabilidades [RP] = 2,53; p = 0,024); C. trachomatis (RP = 3,04; p = 0,009); M. genitalium (RP = 2,37; p = 0,04); e coinfecção por HPV e C. trachomatis (RP = 3,11; p = 0,023). Após a análise multivariada, foi encontrada uma associação significante entre HPV e NIC (RP = 2.48; intervalo de confiança de 95% [IC95%]: 1,04–5,92; p = 0,04) e entre C. trachomatis e NIC (RP = 2,69; IC95%: 1,11–6,53; p = 0,028).

Conclusões A frequência de ISTs foi alta em mulheres assintomáticas. Infecções por HPV e C. trachomatis foram independentemente associadas com a presença de NIC. A alta frequência de ISTs em mulheres assintomáticas sugere a necessidade de rastreamento rotineiro dessas infecções.

 
  • References

  • 1 World Health Organization, Dept. of Reproductive Health and Research. Global Incidence and Prevalence of Selected of Curable Sexually Transmitted Infections. 2008 - Geneve, WHO, 2012. http://www.who.int/reproductivehealth/publications/rtis/stisestimates/en/ . Accessed January 10, 2017.
  • 2 Deluca GD, Basiletti J, Schelover E. , et al. Chlamydia trachomatis as a probable cofactor in human papillomavirus infection in aboriginal women from northeastern Argentina. Braz J Infect Dis 2011; 15 (06) 567-572 Doi: 10.1016/S1413-8670(11)70252-5
  • 3 da Silva Barros NK, Costa MC, Alves RR. , et al. Association of HPV infection and Chlamydia trachomatis seropositivity in cases of cervical neoplasia in Midwest Brazil. J Med Virol 2012; 84 (07) 1143-1150 Doi: 10.1002/jmv.23312
  • 4 Paba P, Bonifacio D, Di Bonito L. , et al. Co-expression of HSV2 and Chlamydia trachomatis in HPV-positive cervical cancer and cervical intraepithelial neoplasia lesions is associated with aberrations in key intracellular pathways. Intervirology 2008; 51 (04) 230-234 Doi: 10.1159/000156481
  • 5 Ashshi AM, Batwa SA, Kutbi SY, Malibary FA, Batwa M, Refaat B. Prevalence of 7 sexually transmitted organisms by multiplex real-time PCR in Fallopian tube specimens collected from Saudi women with and without ectopic pregnancy. BMC Infect Dis 2015; 15: 569-583 Doi: 10.1186/s12879-015-1313-1
  • 6 Nassar FA, Abu-Elamreen FH, Shubair ME, Sharif FA. Detection of Chlamydia trachomatis and Mycoplasma hominis, genitalium and Ureaplasma urealyticum by polymerase chain reaction in patients with sterile pyuria. Adv Med Sci 2008; 53 (01) 80-86 Doi: 10.2478/v10039-008-0020-1
  • 7 Luppi CG, de Oliveira RL, Veras MA, Lippman SA, Jones H, de Jesus CH, Pinho AA, Ribeiro MC, Caiaffa-Filho H. [Early diagnosis and correlations of sexually transmitted infections among women in primarycare health services]. Rev Bras Epidemiol 2011; Sep; 14 (03) 467-477 Doi: 10.1590/S1415-790X2011000300011
  • 8 Greer L, Wendel Jr GD. Rapid diagnostic methods in sexually transmitted infections. Infect Dis Clin North Am 2008; 22 (04) 601-617, v Doi: 10.1016/j.idc.2008.05.010
  • 9 Samra Z, Rosenberg S, Madar-Shapiro L. Direct simultaneous detection of 6 sexually transmitted pathogens from clinical specimens by multiplex polymerase chain reaction and auto-capillary electrophoresis. Diagn Microbiol Infect Dis 2011; 70 (01) 17-21 Doi: 10.1016/j.diagmicrobio.2010.12.001
  • 10 Fredlund H, Falk L, Jurstrand M, Unemo M. Molecular genetic methods for diagnosis and characterisation of Chlamydia trachomatis and Neisseria gonorrhoeae: impact on epidemiological surveillance and interventions. APMIS 2004; 112 (11-12): 771-784 Doi: 10.1111/j.1600-0463.2004.apm11211-1205.x
  • 11 Solomon D, Davey D, Kurman R. , et al; Forum Group Members; Bethesda 2001 Workshop. The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA 2002; 287 (16) 2114-2119 Doi: 10.1001/jama.287.16.2114
  • 12 Sambrook J, Gething MJ. Protein structure. Chaperones, paperones. Nature 1989; 342 (6247): 224-225 Doi: 10.1038/342224a0
  • 13 de Roda Husman AM, Walboomers JM, van den Brule AJ, Meijer CJ, Snijders PJ. The use of general primers GP5 and GP6 elongated at their 3′ ends with adjacent highly conserved sequences improves human papillomavirus detection by PCR. J Gen Virol 1995; 76 (Pt 4): 1057-1062
  • 14 Silva ID, Muniz YC, Sousa MC. , et al. HLA-G 3'UTR polymorphisms in high grade and invasive cervico-vaginal cancer. Hum Immunol 2013; 74 (04) 452-458 Doi: 10.1016/j.humimm.2012.11.025
  • 15 Marks MA, Gupta S, Liaw KL. et al. Prevalence and correlates of HPV among women attending family-planning clinics in Thailand. BMC Infect Dis 2015; Mar 27; 15: 159-170 Doi: 10.1186/s12879-015-0886-z
  • 16 Bellaminutti S, Seraceni S, De Seta F, Gheit T, Tommasino M, Comar M. HPV and Chlamydia trachomatis co-detection in young asymptomatic women from high incidence area for cervical cancer. J Med Virol 2014; 86 (11) 1920-1925 Doi: 10.1002/jmv.24041
  • 17 Rodrigues MM, Fernandes PA, Haddad JP. , et al. Frequency of Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Mycoplasma hominis and Ureaplasma species in cervical samples. J Obstet Gynaecol 2011; 31 (03) 237-241 Doi: 10.3109/01443615.2010.548880
  • 18 Choe HS, Lee DS, Lee SJ. , et al. Performance of Anyplex™ II multiplex real-time PCR for the diagnosis of seven sexually transmitted infections: comparison with currently available methods. Int J Infect Dis 2013; 17 (12) e1134-e1140 Doi: 10.1016/j.ijid.2013.07.011
  • 19 Verteramo R, Pierangeli A, Mancini E. , et al. Human Papillomaviruses and genital co-infections in gynaecological outpatients. BMC Infect Dis 2009; 9: 16-23 Doi: 10.1186/1471-2334-9-16
  • 20 Kharsany AB, Hoosen AA, Moodley J, Bagaratee J, Gouws E. The association between sexually transmitted pathogens and cervical intra-epithelial neoplasia in a developing community. Genitourin Med 1993; 69 (05) 357-360
  • 21 Fernández-Benítez C, Mejuto-López P, Otero-Guerra L, Margolles-Martins MJ, Suárez-Leiva P, Vazquez F. ; Chlamydial Primary Care Group. Prevalence of genital Chlamydia trachomatis infection among young men and women in Spain. BMC Infect Dis 2013; 13: 388-396 Doi: 10.1186/1471-2334-13-388
  • 22 Anagrius C, Loré B, Jensen JS. Mycoplasma genitalium: prevalence, clinical significance, and transmission. Sex Transm Infect 2005; 81 (06) 458-462 Doi: 10.1136/sti.2004.012062
  • 23 Huppert JS, Mortensen JE, Reed JL, Kahn JA, Rich KD, Hobbs MM. Mycoplasma genitalium detected by transcription-mediated amplification is associated with Chlamydia trachomatis in adolescent women. Sex Transm Dis 2008; 35 (03) 250-254 Doi: 10.1097/OLQ.0b013e31815abac6
  • 24 Franceschi S, Herrero R, Clifford GM. , et al. Variations in the age-specific curves of human papillomavirus prevalence in women worldwide. Int J Cancer 2006; 119 (11) 2677-2684
  • 25 Quayle AJ. The innate and early immune response to pathogen challenge in the female genital tract and the pivotal role of epithelial cells. J Reprod Immunol 2002; 57 (1-2): 61-79 Doi: 10.1016/S0165-0378(02)00019-0
  • 26 Silva J, Cerqueira F, Medeiros R. Chlamydia trachomatis infection: implications for HPV status and cervical cancer. Arch Gynecol Obstet 2014; 289 (04) 715-723 Doi: 10.1007/s00404-013-3122-3
  • 27 Fernández G, Martró E, González V. , et al. Usefulness of a novel multiplex real-time PCR assay for the diagnosis of sexually-transmitted infections. Enferm Infecc Microbiol Clin 2016; 34 (08) 471-476 Doi: 10.1016/j.eimc.2015.10.014