AccScience Publishing / EJMO / Volume 6 / Issue 4 / DOI: 10.14744/ejmo.2022.38937
REVIEW

Association of High-risk Human Papillomavirus Titer and Pathogenic Co-infections with Cervical Tissue Cytopathology

Sharon Rachel Wong1 Pei Pei Chong1 Sau Har Lee1,2
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1 School of Biosciences, Faculty of Health and Medical Sciences, Taylor’s University, Selangor, Malaysia
2 Centre for Drug Discovery and Molecular Pharmacology (CDDMP), Faculty of Health and Medical Sciences, Taylor’s University, Selangor, Malaysia
EJMO 2022, 6(4), 282–298; https://doi.org/10.14744/ejmo.2022.38937
Submitted: 31 October 2022 | Accepted: 13 December 2022 | Published: 13 December 2022
© 2022 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Abstract

Human papillomaviruses (HPV) are one of the first viral organisms acknowledged to causing carcinogenesis. Among gynecologic cancers, Pap smear represents a gold standard diagnostic procedure for precancerous cervical lesions. It is efficiently interpreted through a standardized reporting system; The Bethesda System, which aids in distinguishing squamous categories from other entities. Co-infections with other sexually transmitted infections (STIs) could exacerbate cervical lesion severity caused by initial HPV infection as co-infections can lead to distinct reprogramming of host cells and genome integrity. The intricate pathways and effect of the unique cellular microenvironment that HPV and co-infecting STIs create that cause local inflammation and eventually cervical lesion progression will be reviewed in this manuscript. Besides, it is also crucial to consider HPV viral load and distinguish its correlation with cervical lesion severity. Varying amounts of viral titer and its impact on cervical lesions could indicate a mutagenic transformation of the human host cells and HPV. Thus, this review aims to discuss the correlation of co-infections and viral titer on cervical lesion severity and its progression to cancer. Based on these factors, clear clinical reasoning with more effective treatment plans and specific diagnostics can be achieved.

Keywords
Cervical cancer
Cervical lesions
Co-infection
Human papillomavirus
Viral titer
Conflict of interest
None declared.
References

1. Dworzański J, Drop B, Kliszczewska E, Strycharz-Dudziak M, Polz-Dacewicz M. Prevalence of Epstein-Barr virus, human papillomavirus, cytomegalovirus and herpes simplex virus type 1 in patients with diabetes mellitus type 2 in southeastern Poland. PLoS One 2019;14:e0222607. [CrossRef]
2. Krump NA, You J. Molecular mechanisms of viral oncogenesis in humans. Nat Rev Microbiol 2018;16(11):684–98.
3. Charostad J, Nakhaie M, Dehghani A, Faghihloo E. The interplay between EBV and KSHV viral products and NF-κB pathway in oncogenesis. Infect Agent Cancer. 2020;15:62.
4. Schiller JT, Lowy DR. Virus infection and human cancer: an overview. Recent Results Cancer Res 2014;193:1–10. [CrossRef]
5. Mortaki D, Gkegkes ID, Psomiadou V, Blontzos N, Prodromidou A, Lefkopoulos F, et al. Vaginal microbiota and human papillomavirus: a systematic review. J Turk Ger Gynecol Assoc 2020;21:193–200. [CrossRef]
6. Sundström K, Ploner A, Arnheim-Dahlström L, Eloranta S, Palmgren J, Adami HO, et al. Interactions between high- and low-risk HPV Types reduce the risk of squamous cervical cancer. J Natl Cancer Inst 2015;107:djv185. [CrossRef]
7. Obeidat B, Matalka I, Mohtaseb A, Jaradat S, Hayajneh W, Khasawneh R, et al. Prevalence and distribution of high-risk human papillomavirus genotypes in cervical carcinoma, low-grade, and high-grade squamous intraepithelial lesions in Jordanian women. Eur J Gynaecol Oncol 2013;34:257–60.
8. Tao K, Yang J, Yang H, Guo ZH, Hu YM, Tan ZY, et al. Comparative study of the cervista and hybrid capture 2 methods in detecting high-risk human papillomavirus in cervical lesions. Diagn Cytopathol 2014;42:213–7. [CrossRef]
9. Small W Jr, Bacon MA, Bajaj A, Chuang LT, Fisher BJ, Harkenrider MM, et al. Cervical cancer: A global health crisis. Cancer 2017;123:2404–12. [CrossRef]
10. Grabowska AK, Riemer AB. The invisible enemy - how human papillomaviruses avoid recognition and clearance by the host immune system. Open Virol J 2012;6:249–56.
11. Schiffman M, Wentzensen N. Human papillomavirus infection and the multistage carcinogenesis of cervical cancer. Cancer Epidemiol Biomarkers Prev 2013;22:553–60.
12. de Villiers EM. Cross-roads in the classification of papillomaviruses. Virology 2013;445:2–10. [CrossRef]
13. Van Doorslaer K, Li Z, Xirasagar S, Maes P, Kaminsky D, Liou D, et al. The Papillomavirus Episteme: a major update to the papillomavirus sequence database. Nucleic Acids Res 2017;45:D499–506. [CrossRef]
14. Pastrana DV, Peretti A, Welch NL, Borgogna C, Olivero C, Badolato R, et al. Metagenomic discovery of 83 new human papillomavirus types in patients with immunodeficiency. mSphere.2018;3:e00645–18. [CrossRef]
15. Bouvard V, Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F, et al. A review of human carcinogens--Part B: biological agents. The Lancet Oncology 2009;10:321–2. [CrossRef] 
16. Halec G, Schmitt M, Dondog B, Sharkhuu E, Wentzensen N, Gheit T, et al. Biological activity of probable/possible high‐ risk human papillomavirus types in cervical cancer. Int J Cancer 2013;132:63–71.
17. Haedicke J, Iftner T. Human papillomaviruses and cancer. Radiother Oncol 2013;108:397–402. [CrossRef]
18. Mühr LSA, Eklund C, Dillner J. Towards quality and order in human papillomavirus research. Virology. 2018;519:74–6.
19. Bernard HU, Burk RD, Chen Z, Van Doorslaer K, Zur Hausen H, de Villiers EM. Classification of papillomaviruses (PVs) based on 189 PV types and proposal of taxonomic amendments. Virology 2010;401:70–9. [CrossRef]
20. De Villiers E-M, Fauquet C, Broker TR, Bernard H-U, Zur Hausen H. Classification of papillomaviruses. Virology 2004;324:17–27. [CrossRef]
21. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71:209–49.
22. Mustafa WA, Halim A, Nasrudin MW, Ab Rahman KS. Cervical cancer situation in Malaysia: A systematic literature review. Biocell 2022;46:367. [CrossRef]
23. Bruni L AG, Serrano B, Mena M, Gómez D, Muñoz J, Bosch FX, et al. ICO/IARC Information Centre on HPV and Cancer (HPV Information Centre). Human Papillomavirus and Related Diseases in Malaysia. Summary Report 17 June 2019 HPV Information Centre: ICO/IARC Information Centre on HPV and Cancer; 2019. Available at: https://hpvcentre.net/statistics/reports/MYS.pdf. Accessed Dec 29, 2022.
24. Cheong SM, Mohamad Nor NS, Ahmad MH, Manickam M, Ambak R, et al. Improvement of health literacy and intervention measurements among low socio-economic status women: findings from the MyBFF@home study. BMC Womens Health 2018;18:99. [CrossRef]
25. Norrafizah J, Asiah MN, Suraiya S, Zawaha H, Normawati A, Farid BM, et al. Assessment of health literacy among people in a rural area in Malaysia using Newest Vital Signs assessment. J Edu, Society & Behav Scie 2016;16:1–7. [CrossRef]
26. Crosbie EJ, Einstein MH, Franceschi S, Kitchener HC. Human papillomavirus and cervical cancer. The Lancet 2013;382:889–99. [CrossRef]
27. Brianti P, De Flammineis E, Mercuri SR. Review of HPV-related diseases and cancers. New Microbiol 2017;40:80–5.
28. Skinner SR, Wheeler CM, Romanowski B, Castellsagué X, Lazcano-Ponce E, Del Rosario-Raymundo MR, et al; VIVIANE Study Group. Progression of HPV infection to detectable cervical lesions or clearance in adult women: Analysis of the control arm of the VIVIANE study. Int J Cancer 2016;138:2428–38. [CrossRef]
29. World Health Organization (WHO). Comprehensive cervical cancer control: a guide to essential practice. 2nd edition. Available at: https://apps.who.int/iris/bitstream/handle/10665/144785/9789241548953_eng.pdf. Accessed Dec 29, 2022. 
30. Jing Y, Wang T, Chen Z, Ding X, Xu J, Mu X, et al. Phylogeny and polymorphism in the long control regions E6, E7, and L1 of HPV Type 56 in women from southwest China. Mol Med Rep 2018;17:7131–41. [CrossRef]
31. Mirabello L, Clarke MA, Nelson CW, Dean M, Wentzensen N, Yeager M, et al; NCI HPV Workshop, Schiffman M, Burk RD. The intersection of HPV epidemiology, genomics and mechanistic studies of HPV-Mediated carcinogenesis. Viruses 2018;10:80. [CrossRef]
32. Wright JD, Goff B, Falk S. Cervical intraepithelial neoplasia: Terminology, incidence, pathogenesis, and prevention. Lancet 2014;370:1609–21.
33. Solomon D, Davey D, Kurman R, Moriarty A, O'Connor D, Prey M, et al. The 2001 Bethesda System: terminology for reporting results of cervical cytology. Jama 2002;287:2114–9.
34. Khan MJ, Massad LS, Kinney W, Gold MA, Mayeaux EJ Jr, Darragh TM, et al. A common clinical dilemma: Management of abnormal vaginal cytology and human papillomavirus test results. Gynecol Oncol 2016;141:364–70.
35. Egemen D, Cheung LC, Chen X, Demarco M, Perkins RB, Kinney W, et al. Risk estimates supporting the 2019 ASCCP Riskbased management consensus guidelines. J Low Genit Tract Dis 2020;24:132–43. [CrossRef]
36. Nayar R, Wilbur DC. The Bethesda system for reporting cervical cytology: definitions, criteria, and explanatory notes: Springer; 2015.Available at: http://fosp.saude.sp.gov.br:443/docs/The+Bethesda+System+for+Reporting+Cervic.pdf. Accessed Dec 29, 2022. [CrossRef]
37. Ekwueme DU, Uzunangelov VJ, Hoerger TJ, Miller JW, Saraiya M, Benard VB, et al. Impact of the National Breast and Cervical Cancer Early Detection Program on cervical cancer mortality among uninsured low-income women in the US, 1991–2007. American J Preventive Med 2014;47:300–8. 
38. Chiaffarano JM, Alexander M, Rogers R, Zhou F, Cangiarella J, Yee-Chang M, et al. "Low-grade squamous intraepithelial lesion, cannot exclude high-grade:" TBS says "Don't Use It!" should I really stop it? Cytojournal 2017;14:13. [CrossRef]
39. Shidham VB, Kumar N, Narayan R, Brotzman GL. Should LSIL with ASC-H (LSIL-H) in cervical smears be an independent category? A study on SurePath specimens with review of literature. Cytojournal 2007;4:7. [CrossRef]
40. Cheung LC, Egemen D, Chen X, Katki HA, Demarco M, Wiser AL, et al. 2019 ASCCP Risk-Based management consensus guidelines: Methods for risk estimation, recommended management, and validation. J Low Genit Tract Dis 2020;24:90–101. [CrossRef]
41. Gravitt PE, Rositch AF, Silver MI, Marks MA, Chang K, Burke AE, et al. A cohort effect of the sexual revolution may be masking an increase in human papillomavirus detection at menopause in the United States. J Infect Dis 2013;207:272– 80. [CrossRef]
42. Motamedi M, Böhmer G, Neumann HH, von Wasielewski R. CIN III lesions and regression: retrospective analysis of 635 cases. BMC Infect Dis2015;15:1–9. [CrossRef] 
43. Chan CK, Aimagambetova G, Ukybassova T, Kongrtay K, Azizan A. Human papillomavirus infection and cervical cancer: epidemiology, screening, and vaccination—review of current perspectives. J Oncology.2019;2019. 
44. Park KJ. Case Review: Gastric-Type adenocarcinoma of the uterine cervix and precursor lesions. AJSP: Reviews & Reports 2018;23:84–90.
45. Alrajjal A, Pansare V, Choudhury MSR, Khan MYA, Shidham VB. Squamous intraepithelial lesions (SIL: LSIL, HSIL, ASCUS, ASC-H, LSIL-H) of Uterine Cervix and Bethesda System. Cyto- journal 2021;18:16
46. Bosch FX, Lorincz A, Muñoz N, Meijer C, Shah KV. The causal relation between human papillomavirus and cervical cancer. J Clinical Pathology 2002;55:244–65. [CrossRef]
47. Kombe Kombe AJ, Li B, Zahid A, Mengist HM, Bounda GA, Zhou Y, et al. Epidemiology and burden of human papillomavirus and related diseases, molecular pathogenesis, and vaccine evaluation. Front Public Health 2021;8:552028.
48. Aksoy P, Gottschalk EY, Meneses PI. HPV entry into cells. Mutat Res Rev Mutat Res 2017;772:13–22. [CrossRef]
49. Day PM, Schelhaas M. Concepts of papillomavirus entry into host cells. Curr Opin Virol 2014;4:24–31. [CrossRef]
50. Doorbar J, Egawa N, Griffin H, Kranjec C, Murakami I. Human papillomavirus molecular biology and disease association. Rev Med Virol 2015;25:2–23. [CrossRef]
51. Della Fera AN, Warburton A, Coursey TL, Khurana S, McBride AA. Persistent human papillomavirus infection. Viruses 2021;13:321. [CrossRef]
52. Egawa N, Egawa K, Griffin H, Doorbar J. Human papillomaviruses; epithelial tropisms, and the development of neoplasia. Viruses 2015;7:3863–90. [CrossRef]
53. Pinidis P, Tsikouras P, Iatrakis G, Zervoudis S, Koukouli Z, Bothou A, et al. Human papilloma virus’ life cycle and carcinogenesis. Maedica 2016;11:48.
54. Munger K, Baldwin A, Edwards KM, Hayakawa H, Nguyen CL, Owens M, et al. Mechanisms of human papillomavirusinduced oncogenesis. Virology 2004;78:11451–60.
55. von Knebel Doeberitz M. New markers for cervical dysplasia to visualise the genomic chaos created by aberrant oncogenic papillomavirus infections. European J Cancer 2002;38:2229–42. [CrossRef]
56. Graham SV. Human papillomavirus E2 protein: linking replication, transcription, and RNA processing. J Virology 2016;90:8384–8. [CrossRef]
57. Lin M, Ye M, Zhou J, Wang ZP, Zhu X. Recent advances on the molecular mechanism of cervical carcinogenesis based on systems biology technologies. Comput Struct Biotechnol J 2019;17:241–50.
58. Pal A, Kundu R. Human papillomavirus E6 and E7: The cervical cancer hallmarks and targets for therapy. Front Microbiol 2020;10:3116. [CrossRef]
59. Storrs CH, Silverstein SJ. PATJ, a tight junction-associated PDZ protein, is a novel degradation target of high-risk human papillomavirus E6 and the alternatively spliced isoform 18 E6. J Virol 2007;81:4080–90. [CrossRef] 
60. Shanmugasundaram S, You J. Targeting persistent human papillomavirus infection. Viruses 2017;9:229. [CrossRef]
61. Harden ME, Munger K. Human papillomavirus molecular biology. Mutat Res Rev Mutat Res 2017;772:3–12.
62. Sample KM. DNA repair gene expression is associated with differential prognosis between HPV16 and HPV18 positive cervical cancer patients following radiation therapy. Sci Rep 2020;10:2774.
63. Maglennon GA, McIntosh P, Doorbar J. Persistence of viral DNA in the epithelial basal layer suggests a model for papillomavirus latency following immune regression. Virology 2011;414:153–63. [CrossRef]
64. Bergvall M, Melendy T, Archambault J. The E1 proteins. Virology 2013;445:35–56. [CrossRef] 65. McBride AA. The papillomavirus E2 proteins. Virology 2013;445:57–79. [CrossRef]
66. Klingelhutz AJ, Roman A. Cellular transformation by human papillomaviruses: lessons learned by comparing high-and low-risk viruses. Virology 2012;424:77–98. [CrossRef]
67. Shin MK, Sage J, Lambert PF. Inactivating all three rb family pocket proteins is insufficient to initiate cervical cancer. Cancer Res 2012;72:5418–27. [CrossRef]
68. Münger K, Howley PM. Human papillomavirus immortalization and transformation functions. Virus Res. 2002;89:213– 28. [CrossRef]
69. Evbuomwan O, Chowdhury YS. Physiology, Cervical Dilation. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2022. 
70. Reich O, Fritsch H. The developmental origin of cervical and vaginal epithelium and their clinical consequences: a systematic review. J Lower Genital Tract Dis 2014;18:358–60.
71. Prendiville W, Sankaranarayanan R. colposcopy and treatment of cervical precancer. Lyon (FR): International Agency for Research on Cancer; 2017.
72. Prendiville W, Sankaranarayanan R. Anatomy of the uterine cervix and the transformation zone.Ch 2. In: Colposcopy and treatment of cervical precancer. Lyon (FR): International Agency for Research on Cancer; 2017.
73. Ma L, Fisk JM, Zhang RR, Ulukus EC, Crum CP, Zheng W. Eosinophilic dysplasia of the cervix: a newly recognized variant of cervical squamous intraepithelial neoplasia. Am J Surg Pathol 2004;28:1474–84. [CrossRef]
74. Chivukula M, Shidham VB. ASC-H in Pap test-definitive categorization of cytomorphological spectrum. Cytojournal 2006;3:14.
75. Perkins RB, Guido RS, Castle PE, Chelmow D, Einstein MH, Garcia F, et al; 2019 ASCCP Risk-Based Management Consensus Guidelines Committee. 2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors. J Low Genit Tract Dis 2020;24:102–31. [CrossRef]
76. Kannappan S, Lee JH, Rayappan JBB. Methods for screening of cervical cancer: State of Art. In: Rayappan JBB, Lee JH, editors. Biomarkers and Biosensors for Cervical Cancer Diagnosis. Singapore, Springer;2021. [CrossRef]
77. Sawaya GF, Kulasingam S, Denberg TD, Qaseem A. Cervical cancer screening in average-risk women: best practice ad- vice from the Clinical Guidelines Committee of the American College of Physicians. Annals Int Med 2015;162:851–9.
78. Melnikow J, Henderson JT, Burda BU, Senger CA, Durbin S, Weyrich MS. Screening for cervical cancer with high-risk human papillomavirus testing: updated evidence report and systematic review for the US Preventive Services Task Force. Jama 2018;320:687–705. [CrossRef]
79. Gustavsson I, Aarnio R, Berggrund M, Hedlund-Lindberg J, Strand AS, Sanner K, et al. Randomised study shows that repeated self-sampling and HPV test has more than twofold higher detection rate of women with CIN2+ histology than Pap smear cytology. British J Cancer 2018;118:896– 904. [CrossRef]
80. Chong P, Asyikin N, Rusinahayati M, Halimatun S, Rozita R, Ng C, et al. High prevalence of human papillomavirus DNA detected in cervical swabs from women in southern Selangor, Malaysia. Asian Pac J Cancer Prev 2010;11:1645–51.
81. Wolday D, Derese M, Gebressellassie S, Tsegaye B, Ergete W, Gebrehiwot Y, et al. HPV genotype distribution among women with normal and abnormal cervical cytology presenting in a tertiary gynecology referral Clinic in Ethiopia. Infect Agent Cancer 2018;13:28. [CrossRef]
82. Miralpeix E, Genovés J, Solé-Sedeño JM, Mancebo G, Lloveras B, Bellosillo B, et al. Usefulness of p16 INK4a staining for managing histological high-grade squamous intraepithelial cervical lesions. Modern Pathology 2017;30:304–10. 
83. Sun Z, Zhang R, Liu Z, Liu C, Li X, Zhou W, et al. Development of a fluorescence–based multiplex genotyping method for simultaneous determination of human papillomavirus infections and viral loads. BMC Cancer 2015;15:1–11.
84. Chang MS, Oh S, Jung EJ, Park JH, Jeon HW, Lee TS, et al. High‐risk human papillomavirus load and biomarkers in cervical intraepithelial neoplasia and cancer. Apmis 2014;122:427–36. [CrossRef]
85. Wu S, Wu Y, Lu Y, Yue Y, Cui C, Yu M, et al. STAT1 expression and HPV16 viral load predict cervical lesion progression. Oncol Lett 2020;20:28. [CrossRef]
86. Sun CA, Lai HC, Chang CC, Neih S, Yu CP, Chu TY. The significance of human papillomavirus viral load in prediction of histologic severity and size of squamous intraepithelial lesions of uterine cervix. Gynecol Oncol 2001;83:95–9.
87. Long W, Yang Z, Li X, Chen M, Liu J, Zhang Y, et al. HPV-16, HPV-58, and HPV-33 are the most carcinogenic HPV genotypes in Southwestern China and their viral loads are associated with severity of premalignant lesions in the cervix. Virol J 2018;15:94. [CrossRef]
88. Wu Z, Qin Y, Yu L, Lin C, Wang H, Cui J, et al. Association between human papillomavirus (HPV) 16, HPV18, and other HR-HPV viral load and the histological classification of cervical lesions: Results from a large-scale cross-sectional study. J Med Virol 2017;89:535–41.
89. Dalstein V, Riethmuller D, Prétet JL, Le Bail Carval K, Sautière JL, Carbillet JP, et al. Persistence and load of high-risk HPV are predictors for development of high-grade cervical lesions: a longitudinal French cohort study. Int J Cancer 2003;106:396–403. [CrossRef]
90. Lu X, Wang T, Zhang Y, Liu Y. Analysis of influencing factors of viral load in patients with high-risk human papillomavirus. Virol J 2021;18:6. [CrossRef]
91. Singer M, Bulled N, Ostrach B, Mendenhall E. Syndemics and the biosocial conception of health. Lancet 2017;389:941–50.
92. Kim HS, Kim TJ, Lee IH, Hong SR. Associations between sexually transmitted infections, high-risk human papillomavirus infection, and abnormal cervical Pap smear results in OB/ GYN outpatients. J Gynecol Oncol 2016;27:e49.
93. Kiseki H, Tsukahara Y, Tajima N, Tanaka A, Horimoto A, Hashimura N. Influence of co-infection complicated with human papillomavirus on cervical intraepithelial neoplasia development in patients with atypical squamous cells of undetermined significance. J Infect Chemother
2017;23:814–9. [CrossRef]
94. Muvunyi CM, Dhont N, Verhelst R, Crucitti T, Reijans M, Mulders B, et al. Evaluation of a new multiplex polymerase chain reaction assay STDFinder for the simultaneous detection of 7 sexually transmitted disease pathogens. Diagn Microbiol Infect Dis 2011;71:29–37. [CrossRef]
95. Rodriguez-Cerdeira C, Sanchez-Blanco E, Alba A. Evaluation of association between vaginal infections and high-risk human papillomavirus types in female sex workers in Spain. ISRN Obstet Gynecol 2012;2012:240190.
96. Menon S, Broeck DV, Rossi R, Ogbe E, Harmon S, Mabeya H. Associations between vaginal infections and potential highrisk and high-risk human papillomavirus genotypes in female sex workers in Western Kenya. Clin Ther 2016;38:2567– 77.
97. Jensen KE, Thomsen LT, Schmiedel S, Frederiksen K, Norrild B, van den Brule A, et al. 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;90:550–5. [CrossRef]
98. Mayer FL, Wilson D, Hube B. Candida albicans pathogenicity mechanisms. Virulence 2013;4:119–28. [CrossRef]
99. Koskela P, Anttila T, Bjørge T, Brunsvig A, Dillner J, Hakama M, et al. Chlamydia trachomatis infection as a risk factor for invasive cervical cancer. Int J Cancer 2000;85:35–9. 
100. Samoff E, Koumans EH, Markowitz LE, Sternberg M, Sawyer MK, Swan D, Papp JR, Black CM, Unger ER. Association of Chlamydia trachomatis with persistence of high-risk types of human papillomavirus in a cohort of female adolescents. Am J Epidemiol 2005;162:668–75. [CrossRef]
101. Tamim H, Finan RR, Sharida HE, Rashid M, Almawi WY. Cervicovaginal coinfections with human papillomavirus and Chlamydia trachomatis. Diagn Microbiol Infect Dis 2002;43:277–81.
102. 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. [CrossRef]
103. Torcia MG. Interplay among vaginal microbiome, immune response and sexually transmitted viral infections. Int J Mol Sci 2019;20:266.
104. Sood S, Kapil A. An update on Trichomonas vaginalis. Indian J Sexually Transmit Dis and AIDS 2008;29:7–14. [CrossRef]
105. Preethi V, Mandal J, Halder A, Parija SC. Trichomoniasis: An update. Trop Parasitol 2011;1:73–5. [CrossRef]
106. Yang S, Zhao W, Wang H, Wang Y, Li J, Wu X. Trichomonas vaginalis infection-associated risk of cervical cancer: A meta-analysis. Eur J Obstet Gynecol Reprod Biol 2018;228:166– 73.
107. Feng RM, Z Wang M, Smith JS, Dong L, Chen F, Pan QJ, et al. Risk of high-risk human papillomavirus infection and cervical precancerous lesions with past or current trichomonas infection: a pooled analysis of 25,054 women in rural China. J Clin Virol 2018;99-100:84–90.
108. Ghosh I, Muwonge R, Mittal S, Banerjee D, Kundu P, Mandal R, et al. Association between high risk human papillomavirus infection and co-infection with Candida spp. and Trichomonas vaginalis in women with cervical premalignant and malignant lesions. J Clin Virol 2017;87:43–8. [CrossRef] 
109. Lazenby GB, Taylor PT, Badman BS, McHaki E, Korte JE, Soper DE, et al. An association between Trichomonas vaginalis and high-risk human papillomavirus in rural Tanzanian women undergoing cervical cancer screening. Clin Ther 2014;36:38– 45. [CrossRef]
110. 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;86:1920–5.
111. Deluca GD, Basiletti J, Schelover E, Vásquez ND, Alonso JM, Marín HM, et al. Chlamydia trachomatis as a probable cofactor in human papillomavirus infection in aboriginal women from northeastern Argentina. Braz J Infect Dis 2011;15:567–72.
112. Wohlmeister D, Vianna DR, Helfer VE, Gimenes F, Consolaro ME, Barcellos RB, et al. Association of human papillomavirus and Chlamydia trachomatis with intraepithelial alterations in cervix samples. Mem Inst Oswaldo Cruz 2016;111:106–13. [CrossRef]
113. Hanisch RA, Cherne SL, Sow PS, Winer RL, Hughes JP, Feng Q, et al; University of Washington-Dakar HIV and Cervical Cancer Study Group. Human papillomavirus type 16 viral load in relation to HIV infection, cervical neoplasia and cancer in Senegal. Cancer Epidemiol 2014;38:369–75. [CrossRef] 
114. Kim RH, Yochim JM, Kang MK, Shin KH, Christensen R, Park NH. HIV-1 Tat enhances replicative potential of human oral keratinocytes harboring HPV-16 genome. Int J Oncol 2008;33:777–82.
115. Arany I, Grattendick KG, Tyring SK. Interleukin-10 induces transcription of the early promoter of human papillomavirus type 16 (HPV16) through the 5'-segment of the upstream regulatory region (URR). Antiviral Res 2002;55:331– 9. [CrossRef]
116. Crowley-Nowick PA, Ellenberg JH, Vermund SH, Douglas SD, Holland CA, Moscicki AB. Cytokine profile in genital tract secretions from female adolescents: impact of human immunodeficiency virus, human papillomavirus, and other sexually transmitted pathogens. J Infect Dis 2000;181:939– 45. [CrossRef]
117. Mwatelah R, McKinnon LR, Baxter C, Abdool Karim Q, Abdool Karim SS. Mechanisms of sexually transmitted infection-induced inflammation in women: implications for HIV risk. J Int AIDS Soc 2019;22:e25346. [CrossRef]
118. Gupta S, Sodhani P. Reducing "atypical squamous cells" overdiagnosis on cervicovaginal smears by diligent cytology screening. Diagn Cytopathol 2012;40:764–9.
119. Safi Oz Z, Doğan Gun B, Gun MO, Ozdamar SO. Cytomorphometric and morphological analysis in women with trichomonas vaginalis infection: micronucleus frequency in exfoliated cervical epithelial cells. Acta Cytol 2015;59:258–64.
120. Workowski KA, Bachmann LH, Chan PA, Johnston CM, Muzny CA, Park I, et al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep 2021;70:1–187.
121. Burley M, Roberts S, Parish JL. Epigenetic regulation of human papillomavirus transcription in the productive virus life cycle. Semin Immunopathol 2020;42:159–71. [CrossRef]
122. Soto D, Song C, McLaughlin-Drubin ME. Epigenetic alterations in human papillomavirus-associated cancers. Viruses 2017;9:248. [CrossRef]
123. Lleras RA, Smith RV, Adrien LR, Schlecht NF, Burk RD, Harris TM, et al. Unique DNA methylation loci distinguish anatomic site and HPV status in head and neck squamous cell carcinoma. Clin Cancer Res 2013;19:5444–55.
124. Szalmás A, Kónya J. Epigenetic alterations in cervical carcinogenesis. Semin Cancer Biol 2009;19:144–52. [CrossRef]
125. He X, Li S, Shi W, Lin Q, Ma J, Liu Y, et al. Cyclin A1 is associated with poor prognosis in oesophageal squamous cell carcinoma. Oncol Lett 2019;18:706–12. [CrossRef]
126. Kitkumthorn N, Yanatatsanajit P, Kiatpongsan S, Phokaew C, Triratanachat S, Trivijitsilp P, et al. Cyclin A1 promoter hypermethylation in human papillomavirus-associated cervical cancer. BMC Cancer 2006;6:55. [CrossRef]
127. Alibakhshi A, Ranjbari J, Pilehvar-Soltanahmadi Y, Nasiri M, Mollazade M, Zarghami N. An update on phytochemicals in molecular target therapy of cancer: Potential inhibitory ef-fect on telomerase activity. Curr Med Chem 2016;23:2380– 93. 
128. de Wilde J, Kooter JM, Overmeer RM, Claassen-Kramer D, Meijer CJ, Snijders PJ, et al. hTERT promoter activity and CpG methylation in HPV-induced carcinogenesis. BMC Cancer 2010;10:271. [CrossRef]
129. D'Costa ZJ, Jolly C, Androphy EJ, Mercer A, Matthews CM, Hibma MH. Transcriptional repression of E-cadherin by human papillomavirus type 16 E6. PLoS One 2012;7:e48954.
130. Laurson J, Khan S, Chung R, Cross K, Raj K. Epigenetic repression of E-cadherin by human papillomavirus 16 E7 protein. Carcinogenesis 2010;31:918–26. [CrossRef]
131. Rincon-Orozco B, Halec G, Rosenberger S, Muschik D, Nindl I, Bachmann A, et al. Epigenetic silencing of interferon-kappa in human papillomavirus type 16-positive cells. Cancer Res 2009;69:8718–25. [CrossRef]

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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing