Cervical cancer is a preventable cause of cancer with more than half a million women newly diagnosed each year [1]. It is known that cytology (Pap test) test used in cervical cancer screening decreases mortality and incidence [2]. Presence of persistent infection with Human Papilloma Virus (HPV) is associated with precancerous cervical intraepithelial neoplasia (CIN) and is a risk factor for cervical cancer [3]. Low-grade lesions are usually caused by transmission with low risk HPV types; however, persistent infections with higher risk HPV types (HRHPV) lead to high grade lesions [4]. Although persistent infection with HrHPV is an effective cause of cervical cancer; smoking, infection with other sexually transmitted diseases (Clamidya trochomatis, etc.) and hormonal contraception and hormonal imbalances are defined as cofactors that increase the development of cervical cancer when combined with high-grade cervical lesions and HPV infection for the development of cervical cancer [3]. Although there are studies showing the relationship between hormonal contraceptive methods and cervical cancer [5-6], there are conflicting publications on the use of Cooper intrauterine device (Cu-IUD) [7-8]. The aim of this study is to determine the major and minor risk factors for the development of cervical intraepithelial neoplasia in a single center.

HPV positivity was significantly higher in women using COC (p <0.001). Wart incidence was also low in women using Cu-IUD (p <0.001). When the cervical cytology findings of women using COC and Cu-IUD were compared, it was found that the incidence of abnormal cervical cytology in both groups increased compared to the patient group who did not use medical contraceptive method (p <0.001) (Table 2).

This study is a cross-sectional study of data analysis retrospectively, but supported by one-to-one surveys. In addition, while determining the epidemiological factors of patients, a questionnaire was conducted to prevent bias.

The selection of contraceptive methods and the effect of the selected contraceptive methods on the development of CIN and potential risk factors that may affect the development of CIN were investigated in patients who applied to our center. This study, conducted in a large population of Turkish women, is a featured study comparing the effect of contraceptive methods on CIN development and other risk factors causing cervical cancer development.

It is a major factor in HPV CIN development and invasive cervical cancer development [9]. It has been reported that HPV 16 and 18 types cause CIN III development more frequently than HPV 16 than Ot HrHPV types [10]. In our study, HPV positivity, especially HPV 16-18 positivity, has been shown to increase the risk of CIN compared to Ot Hr HPV types.

In a recent metaanalysis, it has been reported that the use of Cu-IUD increases HPV clearance and prevents persistent infection [11]. In our study, HPV positivity was more common in patients using COC.

In a recent study by Loopik et al (2020); reported that there was an increased risk of developing CIN III lesions compared to non-users with both COC use and Cu-IUD use. They also reported that this risk is higher in women using COC compared to women using Cu-IUD [12]. These findings support our study. As a result of colposcopic biopsy in our study, it was found that the frequency of LG-SIL and HG-SIL CIN II lesions were more common in those using COC. In contrast, in the patient group using both COC and Cu-IUD, the rate of HG-SIL CIN III lesion detection was higher than the group not using a medical contraceptive method. In addition, while the frequency of incidence of HGSIL CIN II and CIN III lesions was higher in the patient group using COC in patients with conization compared to those using Cu-IUD; LG-SIL rates were higher in the patient group using Cu-IUD.

In a cross-sectional study examining patients in the California health system; No increase in frequency of HG-SIL CIN II and CIN III lesions was reported in those using Cu-IUD; however, there was an increase in the frequency of HG-SIL CIN II lesions in users of levonorgesterone Intrauterine Device (LNG-IUD). In our study, there was no patient group using LNG-IUD, but contrary to this study, the rate of HG SIL CIN III lesion detection increased in patients using Cu-IUD compared to the group that did not use a medical contraceptive method. In contrast, in our study, the risk of developing CIN in women using Cu-IUD has been shown to be higher than women who use COC. It may be wrong to link it only to HPV positivity. According to the author; multifactorial evaluation is effective in this result.

Previous studies have shown that the use of Cu-IUD causes acute / chronic vaginal and cervical infections, and it has been shown that the vaginal flora changes with the use of Cu-IUD. Moreover, the frequency of bacterial vaginosis in these studies increased in women using Cu- IUD [13-15]. In our study, similar to these studies, there is an increase in the frequency of BV and other infectious agents except trichomonas vaginalis in patients using Cu-IUD. Also, in our study, the frequency of chronic cervicitis increased in both colposcopic biopsy results and conization results in the patient group using Cu-IUD.

In a recent study, the relationship between the presence of vaginal infection and CIN lesions has been investigated, and in these studies, it has been stated that the presence of vaginal infection may be a risk factor for cervical cancer by reducing HPV clearance [16]. In our study, the presence of vaginal infection in regression testing has been shown to play a role in the development of CIN. Given this effect of infection development on CIN, the increased risk for CIN in the patient group using Cu-IUD is not a surprise. It has been reported that smoking is a cofactor that increases the development of CIN in patients using COC [3]. According to the results in our study, smoking increased the risk of developing CIN.

It has been stated that preventing obesity by creating BMI screening programs may decrease the development of cervical cancer [17]. It can be seen in this study that obesity has a minimal contribution to the development of CIN.

In our study, it was found that the level of education also contributed to the development of CIN. According to the author, this may also be related to the socioeconomic cultures of patients. Larger patient groups are needed to investigate this finding.

This study has some limitations. First, this study is a cross-sectional study conducted by examining retrospective data. Therefore, there may be bias in the data. However, this deficiency was tried to be eliminated with the questionnaires. Another limitation is that the study was conducted in a single center. Studies on heterogeneous groups may be required. These limitations need to be considered before generalizing the data.

In conclusion; HPV positivity is still a major risk factor for CIN development. Contraceptive method selection, presence of vaginal infection, smoking and obesity are other risk factors that increase the risk of developing CIN.

I would like to thank Adıyaman University, Department of Obstetrics and Gynecology, assistants who contributed to the collection of study data.

The authors declare no conflict of interest.

04 2 02 87-108 65 2015 10.3322/caac.21262 Torre Lindsey A. Bray Freddie Siegel Rebecca L. Ferlay Jacques Lortet-Tieulent Joannie Jemal Ahmedin CA: A Cancer Journal for Clinicians Global cancer statistics, 2012 14 3 03 147-172 62 2012 10.3322/caac.21139 Saslow Debbie Solomon Diane Lawson Herschel W. Killackey Maureen Kulasingam Shalini L. Cain Joanna Garcia Francisco A. R. Moriarty Ann T. Waxman Alan G. Wilbur David C. Wentzensen Nicolas Downs Levi S. Spitzer Mark Moscicki Anna-Barbara Franco Eduardo L. Stoler Mark H. Schiffman Mark Castle Philip E. Myers Evan R. CA: A Cancer Journal for Clinicians American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer Moscicki A Schiffman M Franceschi S Human Papillomavirus: Proving and Using a Viral Cause for Cancer book 1st Edition; Academic Press (1st pp: 149-160) The Natural History Of Human Papillomavirus Infection In Relation To Cervical Cancer In: David Jenkins, Xavier Bosch (Eds.) 6 06 347-356 9 2009 10.1016/s1473-3099(09)70108-2 Einstein Mark H Schiller John T Viscidi Raphael P Strickler Howard D Coursaget Pierre Tan Tina Halsey Neal Jenkins David The Lancet Infectious Diseases Clinician's guide to human papillomavirus immunology: knowns and unknowns 04 163-175 247 2020 10.1016/j.ejogrb.2020.02.014 Asthana Smita Busa Vishal Labani Satyanarayana European Journal of Obstetrics & Gynecology and Reproductive Biology Oral contraceptives use and risk of cervical cancer—A systematic review & meta-analysis 222 225 11 2018 Khatun SF Khatun S Hossain F et al BSMMU J Prolonged use of oral contraceptive pill, a co-factor for the development of cervical cancer 2 08 130-134 98 2018 10.1016/j.contraception.2018.04.008 Averbach Sarah Silverberg Michael J. Leyden Wendy Smith-McCune Karen Raine-Bennett Tina Sawaya George F. Contraception Recent intrauterine device use and the risk of precancerous cervical lesions and cervical cancer 01 65-69 232 2019 10.1016/j.ejogrb.2018.11.016 Agenjo González Marta Lampaya Nasarre Belén Salazar Fernando Varillas David Cristobal Ignacio European Journal of Obstetrics & Gynecology and Reproductive Biology Influence of intrauterine dispositive in human papillomavirus clearance NA-NA 2009 10.1002/dc.21270 Gupta Nalini Srinivasan Radhika Rajwanshi Arvind Selvaggi Suzanne Diagnostic Cytopathology Functional biomarkers in cervical precancer: An overview 15 12 09 djv257 107 2015 10.1093/jnci/djv257 Wentzensen Nicolas Fetterman Barbara Castle Philip E. Schiffman Mark Wood Shannon N. Stiemerling Eric Tokugawa Diane Bodelon Clara Poitras Nancy Lorey Thomas Kinney Walter Journal of the National Cancer Institute p16/Ki-67 Dual Stain Cytology for Detection of Cervical Precancer in HPV-Positive Women 6 12 1226-1236 130 2017 10.1097/aog.0000000000002307 Cortessis Victoria K. Barrett Malcolm Brown Wade Niquelle Enebish Temuulen Perrigo Judith L. Tobin Jessica Zhong Charlie Zink Jennifer Isiaka Vanessa Muderspach Laila I. Natavio Melissa McKean-Cowdin Roberta Obstetrics & Gynecology Intrauterine Device Use and Cervical Cancer Risk 01 102-109 124 2020 10.1016/j.ejca.2019.10.009 Loopik Diede L. IntHout Joanna Melchers Willem J.G. Massuger Leon F.A.G. Bekkers Ruud L.M. Siebers Albert G. European Journal of Cancer Oral contraceptive and intrauterine device use and the risk of cervical intraepithelial neoplasia grade III or worse: a population-based study 09 1 09 43-48 36 2016 10.1007/s10096-016-2768-8 Donders G. Bellen G. Janssens D. Van Bulck B. Hinoul P. Verguts J. European Journal of Clinical Microbiology & Infectious Diseases Influence of contraceptive choice on vaginal bacterial and fungal microflora 6 06 622.e1-622.e10 218 2018 10.1016/j.ajog.2018.02.017 Achilles Sharon L. Austin Michele N. Meyn Leslie A. Mhlanga Felix Chirenje Zvavahera M. Hillier Sharon L. American Journal of Obstetrics and Gynecology Impact of contraceptive initiation on vaginal microbiota 1-8 2017 2017 10.1155/2017/4919404 Bitew Adane Abebaw Yeshiwork Bekele Delayehu Mihret Amete International Journal of Microbiology Prevalence of Bacterial Vaginosis and Associated Risk Factors among Women Complaining of Genital Tract Infection 28 2 10 323-327 202 2019 10.1007/s00203-019-01747-4 Kovachev Stefan Miladinov Archives of Microbiology Cervical cancer and vaginal microbiota changes 20 12 04 1184-1191 36 2018 10.1200/jco.2017.75.3442 Clarke Megan A. Fetterman Barbara Cheung Li C. Wentzensen Nicolas Gage Julia C. Katki Hormuzd A. Befano Brian Demarco Maria Schussler John Kinney Walter K. Raine-Bennett Tina R. Lorey Thomas S. Poitras Nancy E. Castle Philip E. Schiffman Mark Journal of Clinical Oncology Epidemiologic Evidence That Excess Body Weight Increases Risk of Cervical Cancer by Decreased Detection of Precancer