Infectious Disorders - Drug Targets

Author(s): Mona Moharreri and Amir Sohrabi*

DOI: 10.2174/1871526520666191231142317

Characteristics of HSV-2, M. genitalium and C. trachomatis in HPV Genotypes Associated with Cervical Intraepithelial Neoplasia and Genital Infections

Page: [112 - 118] Pages: 7

  • * (Excluding Mailing and Handling)

Abstract

Background: Cervical cancer is the most common cancer in women. High-Risk HPV types are known as the main agents involved in genital and cervical malignancies. There may be co pathogens like STIs that are involved in enhancing the susceptibility and progression to cervical neoplasia. This study was conducted to detect C. trachomatis, HSV-2 and M. genitalium using qPCR in women suffering from cervical intraepithelial neoplasia, HPV infection and non cancerous- non HPV subjects for the association of burden of genital disorders.

Materials and Methods: This descriptive study was performed on 195 Liquid Based Cytology (LBCs) specimens collected from women referred to private laboratories. Fifty, 98 and 47 samples were from women with known CIN, HPV positive and non-cancerous/non-HPV, respectively. HSV-2, C. trachomatis, M. genitalium and HPV genotypes have been detected using multiplex TaqMan Real Time PCR and PCR hybridization.

Results: A total of 148 HPV positive samples were included. HPVs 6 (35.13%), 16 (32.43%), 18 (21.62%), 11 (9.46%), 31 (9.46%), and 51 (9.46%) were the most common genotypes. Single, 2, 3, and more than 4 multiple HPV genotypes were detected in 46%, 29.7%, 14.2%, 10.1% cases, respectively. The prevalence of M. genitalium, C. trachomatis and HSV2 was 3 (1.54%), 24 (12.3%) and 1(0.5%), respectively. There were no statistically significant differences between these pathogens and cervical intraepithelial neoplasia (p≥ 0.05).

Conclusion: HR-HPV genotypes were more prevalent in genital infections and cervical cancer. It would seem early detection of dominant STI pathogens such as Chlamydia spp. gains due to effective prevention. Here, further research is needed to understand the co-infections burden of HPV genotypes with STIs in clinical manifestations.

Keywords: HPV, HSV-2, M. genitalium, C. trachomatis, cervical cancer, genital infection, Iran.

Graphical Abstract

[1]
Bouvard, V.; Baan, R.; Straif, K.; Grosse, Y.; Secretan, B.; El Ghissassi, F.; Benbrahim-Tallaa, L.; Guha, N.; Freeman, C.; Galichet, L.; Cogliano, V. WHO International Agency for Research on Cancer Monograph Working Group. A review of human carcinogens--Part B: biological agents. Lancet Oncol., 2009, 10(4), 321-322.
[http://dx.doi.org/10.1016/S1470-2045(09)70096-8] [PMID: 19350698]
[2]
Sohrabi, A.; Mirab-Samiee, S.; Rahnamaye-Farzami, M.; Rafizadeh, M.; Akhavan, S.; Hashemi-Bahremani, M.; Modarresl, M.H. C13orf18 and C1orf166 (MULAN) DNA genes methylation are not associated with cervical cancer and precancerous lesions of human papillomavirus genotypes in Iranian women. Asian Pac. J. Cancer Prev., 2014, 15(16), 6745-6748.
[http://dx.doi.org/10.7314/APJCP.2014.15.16.6745] [PMID: 25169519]
[3]
Shayanfar, N.; Hosseini, N.; Panahi, M.; Azadmanesh, K.; Mohammadpour, M.; Kadivar, M.; Mirzaie, A.Z.; Sohrabi, A. Detection of mucosal type human papillomavirus in cutaneous squamous cell carcinoma in Iran. Pathol. Res. Pract., 2013, 209(2), 90-94.
[http://dx.doi.org/10.1016/j.prp.2012.10.010] [PMID: 23218763]
[4]
Arnheim, D.L.; Andersson, K.; Luostarinen, T.; Thoresen, S.; Ögmundsdottír, H.; Tryggvadottír, L.; Wiklund, F.; Skare, G.B.; Eklund, C.; Sjölin, K.; Jellum, E.; Koskela, P.; Wadell, G.; Lehtinen, M.; Dillner, J. Prospective seroepidemiologic study of human papillomavirus and other risk factors in cervical cancer. Cancer Epidemiol. Biomarkers Prev., 2011, 20(12), 2541-2550.
[http://dx.doi.org/10.1158/1055-9965.EPI-11-0761] [PMID: 21994401]
[5]
Doorbar, J.; Egawa, N.; Griffin, H.; Kranjec, C.; Murakami, I. Human papillomavirus molecular biology and disease association. Rev. Med. Virol., 2015, 25(Suppl. 1), 2-23.
[http://dx.doi.org/10.1002/rmv.1822] [PMID: 25752814]
[6]
Coser, J.; Boeira, T.R.; Wolf, J.M.; Cerbaro, K.; Simon, D.; Lunge, V.R. Cervical human papillomavirus infection and persistence: a clinic-based study in the countryside from South Brazil. Braz. J. Infect. Dis., 2016, 20(1), 61-68.
[http://dx.doi.org/10.1016/j.bjid.2015.10.008] [PMID: 26706020]
[7]
Abdolmaleki, M.; Sohrabi, A. Characterization of JAK2 V617F (1849 G > T) mutation in cervical cancer related to human papillomavirus and sexually transmitted infections. J. Cancer Prev., 2018, 23(2), 82-86.
[http://dx.doi.org/10.15430/JCP.2018.23.2.82] [PMID: 30003068]
[8]
Castellsagué, X.; Pawlita, M.; Roura, E.; Margall, N.; Waterboer, T.; Bosch, F.X.; de Sanjosé, S.; Gonzalez, C.A.; Dillner, J.; Gram, I.T.; Tjønneland, A.; Munk, C.; Pala, V.; Palli, D.; Khaw, K.T.; Barnabas, R.V.; Overvad, K.; Clavel-Chapelon, F.; Boutron-Ruault, M.C.; Fagherazzi, G.; Kaaks, R.; Lukanova, A.; Steffen, A.; Trichopoulou, A.; Trichopoulos, D.; Klinaki, E.; Tumino, R.; Sacerdote, C.; Mattiello, A. Bueno-de-Mesquita HB, Peeters PH, Lund E, Weiderpass E, Quirós JR, Sánchez MJ, Navarro C, Barricarte A,Larrañaga N, Ekström J, Hortlund M, Lindquist D, Wareham N, Travis RC, Rinaldi S, Tommasino M, Franceschi S, Riboli E. Prospective sero epidemiologic study on the role of Human Papillomavirus and other infections in cervical carcinogenesis: evidence from the EPIC cohort. Int. J. Cancer, 2014, 135, 440-452.
[PMID: 24338606]
[9]
Wohlmeister, D.; Vianna, D.R.; Helfer, V.E.; Gimenes, F.; Consolaro, M.E.; Barcellos, R.B.; Rossetti, M.L.; Calil, L.N.; Buffon, A.; Pilger, D.A. Association of human papillomavirus and Chlamydia trachomatis with intraepithelial alterations in cervix samples. Mem. Inst. Oswaldo Cruz, 2016, 111(2), 106-113.
[http://dx.doi.org/10.1590/0074-02760150330] [PMID: 26841046]
[10]
Sexually Transmitted Diseases Treatment Guidelines CDC 2015. Available from: https://www.cdc.gov/std/tg2015
[11]
Shayanfar, N.; Babaheidarian, P.; Rahmani, H.; Azadmanesh, K.; Sohrabi, A.; Mohammadpour, M.; Mirzaie, A.Z.; Parvaneh, N. Epidermodysplasia verruciformis associated with plasmablastic lymphoma and hepatitis B virus infection. Acta Dermatovenerol. Croat., 2012, 20(4), 267-271.
[PMID: 23317490]
[12]
Ghosh, I.; Mandal, R.; Kundu, P.; Biswas, J. Association of genital infections other than human papillomavirus with pre-invasive and invasive cervical neoplasia. J. Clin. Diagn. Res., 2016, 10(2), XE01-XE06.
[http://dx.doi.org/10.7860/JCDR/2016/15305.7173] [PMID: 27042571]
[13]
Seraceni, S.; De Seta, F.; Colli, C.; Del Savio, R.; Pesel, G.; Zanin, V.; D’Agaro, P.; Contini, C.; Comar, M. High prevalence of hpv multiple genotypes in women with persistent chlamydia trachomatis infection. Infect. Agent. Cancer, 2014, 9, 30.
[http://dx.doi.org/10.1186/1750-9378-9-30] [PMID: 25621003]
[14]
Falk, L.; Fredlund, H.; Jensen, J.S. Signs and symptoms of urethritis and cervicitis among women with or without Mycoplasma genitalium or Chlamydia trachomatis infection. Sex. Transm. Infect., 2005, 81(1), 73-78.
[http://dx.doi.org/10.1136/sti.2004.010439] [PMID: 15681728]
[15]
Zarei, O.; Rezania, S.; Mousavi, A. Mycoplasma genitalium and cancer: a brief review. Asian Pac. J. Cancer Prev., 2013, 14(6), 3425-3428.
[http://dx.doi.org/10.7314/APJCP.2013.14.6.3425] [PMID: 23886122]
[16]
Smith, J.S.; Herrero, R.; Bosetti, C.; Muñoz, N.; Bosch, F.X.; Eluf-Neto, J.; Castellsagué, X.; Meijer, C.J.L.M.; Van den Brule, A.J.C.; Franceschi, S.; Ashley, R. International Agency for Research on Cancer (IARC) Multicentric Cervical Cancer Study Group. Herpes simplex virus-2 as a human papillomavirus cofactor in the etiology of invasive cervical cancer. J. Natl. Cancer Inst., 2002, 94(21), 1604-1613.
[http://dx.doi.org/10.1093/jnci/94.21.1604] [PMID: 12419786]
[17]
Sohrabi, A.; Mirab-Samiee, S.; Modarresi, M.H.; Izadimood, N.; Azadmanesh, K.; Rahnamaye-Farzami, M. Development of in-house multiplex real time PCR for human papillomavirus genotyping in Iranian women with cervical cancer and cervical intraepithelial neoplasia. Asian Pac. J. Cancer Prev., 2014, 15(15), 6257-6261.
[http://dx.doi.org/10.7314/APJCP.2014.15.15.6257] [PMID: 25124608]
[18]
Sohrabi, A.; Hajia, M.; Jamali, F.; Kharazi, F. Is incidence of multiple HPV genotypes rising in genital infections? J. Infect. Public Health, 2017, 10(6), 730-733.
[http://dx.doi.org/10.1016/j.jiph.2016.10.006] [PMID: 28215919]
[19]
Dickson, E.L.; Vogel, R.; Bliss, R.; Downs, L.S. Jr Multiple-type HPV infections: a cross sectional analysis of the prevalence of specific types in 309,000 women referred for HPV testing at the time of cervical cytology. Int. J. Gynecol. Cancer, 2013, 23, 1295-1302.
[http://dx.doi.org/10.1097/IGC.0b013e31829e9fb4] [PMID: 23970156]
[20]
Sohrabi, A.; Hajia, M. Cervical cancer and genital infections: assessment of performance and validation in human papillomavirus genotyping assays in Iran, its Neighbouring countries and persian gulf area. Iran. J. Pathol., 2017, 12(1), 35-44.
[PMID: 29760751]
[21]
Zamani, S.; Sohrabi, A.; Rahnamaye-Farzami, M.; Hosseini, S.M. Glutathione S-transferase omega gene polymorphism as a biomarker for human papilloma virus and cervical cancer in Iranian women. J. Turk. Ger. Gynecol. Assoc., 2018, 19(4), 193-200.
[http://dx.doi.org/10.4274/jtgga.2018.0056] [PMID: 30115608]
[22]
Zamani, S.; Sohrabi, A.; Hosseini, S.M.; Rahnamaye-Farzami, M.; Akbari, A. Deregulation of miR-21 and miR-29a in Cervical Cancer Related to HPV Infection. MicroRNA, 2019, 8(2), 110-115.
[http://dx.doi.org/10.2174/2211536607666181017124349] [PMID: 30332981]
[23]
Szostek, S.; Zawilińska, B.; Klimek, M.; Kopeć, J.; Kosz-Vnenchak, M. Is the presence of herpesviruses in cervical secretions a prognostic factor for cervical pathology in HPV-positive women? Przegl. Epidemiol., 2009, 63(1), 97-101.
[PMID: 19522235]
[24]
Kwaśniewska, A.; Korobowicz, E.; Zdunek, M.; Skoczyński, M.; Kwaśniewski, W.; Daniłoś, J.; Goździcka-Józefiak, A. Prevalence of Chlamydia trachomatis and herpes simplex virus 2 in cervical carcinoma associated with human papillomavirus detected in paraffin-sectioned samples. Eur. J. Gynaecol. Oncol., 2009, 30(1), 65-70.
[PMID: 19317260]
[25]
Malary, M.; Abedi, G.; Hamzehgardeshi, Z.; Afshari, M.; Moosazadeh, M. The prevalence of herpes simplex virus type 1 and 2 infection in Iran: A meta-analysis. Int. J. Reprod. Biomed. (Yazd), 2016, 14(10), 615-624.
[http://dx.doi.org/10.29252/ijrm.14.10.615] [PMID: 27921084]
[26]
Ahmadi, M.; Rasi, H.; Mostafazadeh, M.; Hajazimian, S.; Maroufi, N.F.; Nahaei, M.R.; Rahaee, S.; Isazadeh, A. Analysis of cervical lesions for presence of HSV-2 and HPV-16 and HPV-18 in Iranian patients by PCR. Horm. Mol. Biol. Clin. Investig., 2017, 31(3), 1-7.
[http://dx.doi.org/10.1515/hmbci-2017-0019] [PMID: 28609291]
[27]
Sohrabi, A.; Rahnamaye-Farzami, M.; Mirab-Samiee, S.; Mahdavi, S.; Babaei, M. Comparison of In-House Multiplex Real Time PCR, Diagcor Geno Flow HPV Array test and INNO-LiPA HPV Genotyping Extra Assays with LCD- Array kit for human papillomavirus genotyping in cervical liquid based cytology specimens and genital lesions in Tehran, Iran. Clin. Lab., 2016, 62(4), 615-619.
[PMID: 27215080]
[28]
Roshani, D.; Ramazanzadeh, R.; Farhadifar, F.; Ahmadi, A.; Derakhshan, S.; Rouhi, S.; Zarea, S.; Zandvakili, F. A PRISMA systematic review and meta-analysis on Chlamydia trachomatis infections in Iranian women (1986-2015). Medicine (Baltimore), 2018, 97(16)e0335
[http://dx.doi.org/10.1097/MD.0000000000010335] [PMID: 29668583]
[29]
Javanmard, D.; Behravan, M.; Ghannadkafi, M.; Salehabadi, A.; Ziaee, M.; Namaei, M.H. Detection of chlamydia trachomatis in pap smear samples from south Khorasan province of Iran. Int. J. Fertil. Steril., 2018, 12(1), 31-36.
[PMID: 29334204]
[30]
Azami, M.; Badfar, G.H.; Mansouri, A.; Yekta Kooshali, M.H.; Kooti, W.; Tardeh, Z.; Soleymani, A.; Abbasalizadeh, S.H. Prevalence of chlamydia trachomatis in pregnant iranian women: A Systematic review and meta-analysis. Int. J. Fertil. Steril., 2018, 12(3), 191-199.
[PMID: 29935063]
[31]
Farivar, T.N.; Johari, P. Lack of association between Chlamydia trachomatis infection and cervical cancer--Taq Man realtime PCR assay findings. Asian Pac. J. Cancer Prev., 2012, 13(8), 3701-3704.
[http://dx.doi.org/10.7314/APJCP.2012.13.8.3701] [PMID: 23098457]
[32]
Sohrabi, A. Rahnamaye, F.; Mirab S.S.; Modarressi MH. An overview on papillomaviruses as the main cause of cervical cancer. Majallah-i Zanan, Mamai va Nazai-i Iran, 2015, 18, 14-25.
[33]
Jensen, K.E.; Thomsen, L.T.; Schmiedel, S.; Frederiksen, K.; Norrild, B.; van den Brule, A.; Iftner, T.; Kjær, S.K. Chlamydia trachomatis and risk of cervical intraepithelial neoplasia grade 3 or worse in women with persistent human papillomavirus infection: a cohort study. Sex. Transm. Infect., 2014, 90(7), 550-555.
[http://dx.doi.org/10.1136/sextrans-2013-051431] [PMID: 24728044]
[34]
Vielot, N.; Hudgens, M.G.; Mugo, N.; Chitwa, M.; Kimani, J.; Smith, J. The role of chlamydia trachomatis in high-risk human papillomavirus persistence among female sex workers in nairobi, Kenya. Sex. Transm. Dis., 2015, 42(6), 305-311.
[http://dx.doi.org/10.1097/OLQ.0000000000000287] [PMID: 25970306]
[35]
Manhart, L.E. Diagnostic and resistance testing for Mycoplasma genitalium: what will it take? Clin. Infect. Dis., 2014, 59(1), 31-33.
[http://dx.doi.org/10.1093/cid/ciu224] [PMID: 24729505]
[36]
Biernat-Sudolska, M.; Szostek, S.; Rojek-Zakrzewska, D.; Klimek, M.; Kosz-Vnenchak, M. Concomitant infections with human papillomavirus and various mycoplasma and ureaplasma species in women with abnormal cervical cytology. Adv. Med. Sci., 2011, 56(2), 299-303.
[http://dx.doi.org/10.2478/v10039-011-0028-9] [PMID: 21940266]
[37]
Pisani, S.; Gallinelli, C.; Seganti, L.; Lukic, A.; Nobili, F.; Vetrano, G.; Imperi, M.; Degener, A.M.; Chiarini, F. Detection of viral and bacterial infections in women with normal and abnormal colposcopy. Eur. J. Gynaecol. Oncol., 1999, 20(1), 69-73.
[PMID: 10422688]
[38]
Ona, S.; Molina, R.L.; Diouf, K. Mycoplasma genitalium: an overlooked sexually transmitted pathogen in women? Infect. Dis. Obstet. Gynecol., 2016.20164513089
[http://dx.doi.org/10.1155/2016/4513089] [PMID: 27212873]
[39]
Dehon, P.M.; McGowin, C.L. Mycoplasma genitalium infection is associated with microscopic signs of cervical inflammation in liquid cytology specimens. J. Clin. Microbiol., 2014, 52(7), 2398-2405.
[http://dx.doi.org/10.1128/JCM.00159-14] [PMID: 24759719]
[40]
Hajia, M.; Sohrabi, A. Possible synergistic interactions among multiple HPV genotypes in women suffering from genital neoplasia. Asian Pac. J. Cancer Prev., 2018, 19(3), 785-789.
[PMID: 29582635]
[41]
Rahimkhani, M.; Mordadi, A.; Gilanpour, M. Detection of urinary chlamydia trachomatis, Mycoplasma genitalium and human papilloma virus in the first trimester of pregnancy by PCR method. Ann. Clin. Microbiol. Antimicrob., 2018, 17(1), 25.
[http://dx.doi.org/10.1186/s12941-018-0276-7] [PMID: 29866110]
[42]
Behzadi, M.A.; Davarpanah, M.A.; Namayandeh, M.; Pourabbas, B.; Allahyari, S.; Ziyaeyan, M. Molecular diagnosis of genital tract infections among HIV-positive women in Iran. Iran. J. Microbiol., 2018, 10(4), 233-241.
[PMID: 30483375]