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Status of HPV Vaccination Among HPV-Infected Women Aged 20–60 Years with Abnormal Cervical Cytology in South Korea: a Multicenter, Retrospective Study

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Status of HPV Vaccination Among HPV-Infected Women Aged 20–60 Years with Abnormal Cervical Cytology in South Korea: a Multicenter, Retrospective Study J Gynecol Oncol. 2020 Jan;31(1):e4 https://doi.org/10.3802/jgo.2020.31.e4 pISSN 2005-0380·eISSN 2005-0399 Original Article Status of HPV vaccination among HPV-infected women aged 20–60 years with abnormal cervical cytology in South Korea: a multicenter, retrospective study Jaehyun Seong ,1 Sangmi Ryou ,1 Myeongsu Yoo ,1 JeongGyu Lee ,1 Kisoon Kim ,1 Youngmee Jee ,2 Chi Heum Cho ,3 Seok Mo Kim ,4 Sung Ran Hong ,5 Dae Hoon Jeong ,6 Won-Chul Lee ,7 Jong Sup Park ,8 Tae Jin Kim ,9 Mee-Kyung Kee 1 1Division of Viral Diseases Research, Center for Infectious Diseases Research, Korea National Institute of Received: Feb 1, 2019 Health, Cheongju, Korea Revised: Jun 12, 2019 2Center for Infectious Diseases Research, Korea National Institute of Health, Cheongju, Korea Accepted: Jun 19, 2019 3Department of Obstetrics and Gynecology, Keimyung University Dongsan Medical Center, Daegu, Korea 4Department of Obstetrics and Gynecology, Chonnam National University Medical School, Gwangju, Korea Correspondence to 5Department of Pathology, Cheil General Hospital and Women's Healthcare Center, Dankook University Mee-Kyung Kee College of Medicine, Seoul, Korea Division of Viral Disease Research, Center for 6Department of Obstetrics and Gynecology, Inje University Busan Paik Hospital, University College of Infectious Diseases Research, Korea National Medicine, Busan, Korea Institute of Health, 187 Osongsaengmyeong 7Department of Preventive Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea 2-ro, Osong-eup, Heungdeok-gu, 8Department of Obstetrics and Gynecology, Seoul St. Mary's Hospital, The Catholic University of Korea Cheongju 28159, Korea. College of Medicine, Seoul, Korea 9 E-mail: [email protected] Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Dankook University, Seoul, Korea Copyright © 2020. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology ABSTRACT This is an Open Access article distributed under the terms of the Creative Commons Objectives: Since 2007, human papillomavirus (HPV) vaccines have been administered for Attribution Non-Commercial License (https:// the prevention of cervical cancer in Korea. We investigated the status of HPV vaccination creativecommons.org/licenses/by-nc/4.0/) among HPV-infected adult women with abnormal cervical cytology before the introduction of which permits unrestricted non-commercial National Immunization Program. use, distribution, and reproduction in any Methods: medium, provided the original work is properly From 2010 to 2016, HPV-positive women (age, 20–60 years) with atypical cited. squamous cells of undetermined significance or low-grade squamous intraepithelial lesion (LSIL) were enrolled from five hospitals across Korea. Their HPV genotype, epidemiologic, ORCID iDs and clinical data, including HPV vaccination history, were obtained. We compared the Jaehyun Seong https://orcid.org/0000-0003-2345-3937 epidemiological characteristics and prevalence of HPV-16/18 genotypes between vaccinated Sangmi Ryou and unvaccinated women. https://orcid.org/0000-0001-9997-9420 Results: Among the 1,300 women, approximately 26% had a history of vaccination. Myeongsu Yoo Vaccinated patients were significantly younger, unmarried, and had a higher education https://orcid.org/0000-0001-8542-8898 level than unvaccinated women. For HPV-vaccinated individuals by vaccine dose, there was JeongGyu Lee a significant younger age at vaccination initiation (p=0.025), longer duration from HPV https://orcid.org/0000-0002-7213-6797 Kisoon Kim vaccination to Pap test date (p=0.001), and lower proportion of HPV-16/18 (p=0.028) in the https://orcid.org/0000-0002-5387-8074 women with three doses. There was a significantly lower prevalence of HPV-16/18 genotypes in women who were vaccinated at least 12 months prior than in unvaccinated women https://ejgo.org 1/10 Status of HPV vaccination among HPV-infected women Youngmee Jee (adjusted prevalence ratio [aPR]=0.51; 95% confidence interval [CI]=0.29–0.88). For women https://orcid.org/0000-0001-5369-6628 with LSIL, the prevalence of the HPV-16/18 genotypes was significantly lower in women who Chi Heum Cho were vaccinated more than 12 months prior than in unvaccinated women (aPR=0.35; 95% https://orcid.org/0000-0002-0437-4099 Seok Mo Kim CI=0.13–0.96). https://orcid.org/0000-0003-2318-0334 Conclusion: This study highlighted the status of HPV vaccination and the prevalence of HPV- Sung Ran Hong 16/18 genotypes among HPV-infected women with abnormal cervical cytology according to https://orcid.org/0000-0002-6828-2345 HPV vaccination. It provides preliminary information regarding the status of HPV vaccination Dae Hoon Jeong among Korean adult women. https://orcid.org/0000-0001-9354-5496 Won-Chul Lee Keywords: HPV; Vaccination; Adult; Korea; Genotype https://orcid.org/0000-0002-5483-1614 Jong Sup Park https://orcid.org/0000-0003-4086-4885 Tae Jin Kim INTRODUCTION https://orcid.org/0000-0002-5322-2745 Mee-Kyung Kee https://orcid.org/0000-0001-7361-8811 Human papillomavirus (HPV) infection is the main cause of cervical cancer, with an estimated 530,000 cases worldwide in 2012. There were 266,000 deaths due to cervical Funding cancer, accounting for 8% of all cancer-attributed deaths in women that year [1]. In Korea in This study was supported by a fund from 2015, 3,582 new cervical cancer cases were reported with 967 cervical cancer deaths. Cervical the Chronic Infectious Disease Cohort Study (4800-4859-304) from the Korea Centers for cancer is a disease associated with significant patient burden, and in 2015, it was the third Disease Control and Prevention. most common cancer in Korean women aged 15–34 years [2,3]. Between 2004 and 2015, the prevalence of cervical cancer in Korean women declined; however, the number of patients Conflict of Interest diagnosed with carcinoma in situ, cervical intraepithelial neoplasia 1, 2, not designated No potential conflict of interest relevant to this as cervical cancer, increased 2-fold during the same period [4]. Additionally, the overall article was reported. prevalence of HPV infection in Korean women was 34.2%, with 49.9% of women aged 18–29 Author Contributions years infected [5]. By March 2017, 2 vaccines, Gardasil and Cervarix, had been introduced Data curation: S.J., L.W.C.; Formal analysis: to prevent cervical cancer as part of a National Immunization Program (NIP) in 71 countries S.J., Y.M.; Funding acquisition: K.K., J.Y.; worldwide [6]. In Korea, these vaccines have been available since 2007 after obtaining Investigation: P.J.S., K.T.J.; Methodology: R.S., K.M.K.; Project administration: K.K., P.J.S., approval from the Ministry of Food and Drug Safety, and have been included as part of a NIP K.T.J., K.M.K.; Resources: C.C.H., K.S.M., to vaccinate girls aged 12 years in 2016 [7]. Both vaccines were known to have a preventive H.S.R., J.D.H.; Software: L.J.; Supervision: J.Y.; effect on the HPV-16/18 genotypes that cause 70% of the cervical cancers [8]. Because Writing - original draft: S.J.; Writing - review & insurance providers do not cover the cost of HPV vaccinations and some women prefer to editing: R.S., K.M.K. be vaccinated privately (i.e., outside of the NIP) according to the recommendations of their gynecologist, there is a paucity of information regarding HPV vaccination status in Korea. Because HPV genotype distribution varies according to geographic region and race [9], it is necessary to determine the impact of vaccination. There is limited research on the extent and the status of HPV vaccination in Korea. In light of this, it is necessary to investigate the status of HPV vaccinations among Korean women. Therefore, we analyzed HPV vaccination status among HPV-infected Korean women aged ≥20 years, and the prevalence of vaccine-targeted HPV genotypes according to HPV vaccination before the introduction of NIP. MATERIALS AND METHODS 1. Materials We used data collected from the Korea HPV cohort study, which is a multicenter study, undertaken within the obstetrics department at five general hospitals across Korea in 2009 to identify high risk factors of cervical disease progression (until the stage of high-grade squamous intraepithelial lesions [HSILs]) among HPV-infected adult Korean women. The https://ejgo.org https://doi.org/10.3802/jgo.2020.31.e4 2/10 Status of HPV vaccination among HPV-infected women , HPV-infected women aged years and diagnosed with ASCUS or LSIL Unknown HPV vaccination history , HPV vaccination history Vaccinated Not vaccinated Unknown results of HPV DNA genotype or missing of the Unknown results of date of HPV DNA genotype ASCUS/LSIL diagnosis HPV DNA genotype HPV DNA genotype Fig. 1. Flow chart of study design of the status of HPV vaccination among HPV-infected adults women in Korea. ASCUS, atypical squamous cells of undetermined significance; HPV, human papillomavirus; LSIL, low-grade squamous intraepithelial lesion. HPV cohort study registered subjects who satisfied the following inclusion criteria. First, the participants were Korean women aged 20–60 years with a DNA test positive for HPV regardless of HPV genotype, and second, HPV-infected women were diagnosed with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) via a Papanicolaou (Pap) test [10]. From 2010 to 2016, out of 1,325 registered adult women in the cohort study, 1,300 women who responded to questions about their HPV vaccination history were selected as individuals for this study. To compare the prevalence of HPV genotypes by HPV vaccination, we collected data from 1,181 women by carrying out HPV genotyping after HPV vaccination (Fig. 1). Each of the 5 hospitals obtained approval from their Institutional Review Board (IRB) to participate in the HPV cohort study.
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