Introduction: We previously reported that preoperative human papillomavirus (HPV) type 16/18 positivity and postoperative high-risk (HR)-HPV test positivity are associated with abnormal postoperative cytology. In this study, we further examined whether preoperative and postoperative HR-HPV genotyping could predict cytological abnormalities and the risk of additional surgery. Methods: Patients who underwent cervical conization at our hospital between July 2009 and June 2018 were enrolled. HPV genotyping was performed preoperatively for all patients with HPV-positive. The association among preoperative and postoperative HR-HPV genotyping results, the cumulative risk of cytological abnormalities, and additional surgery were evaluated. The endpoint approach was used to investigate the cumulative incidence of additional surgery owing to cytological abnormalities, such as low-grade squamous intraepithelial lesion positivity and recurrence 2 years after cervical conization. Results: Positive and negative histological margins were observed in 21 and 287 of 308 cases, respectively. The cumulative incidence of abnormal cytology and additional surgery was significantly higher in margin-positive cases than that in margin-negative cases. Examination established according to the margin status demonstrated that the postoperative HR-HPV-positive group had a significantly worse prognosis than the HR-HPV-negative group. Additionally, 32 cases, wherein the same genotype detected before and after surgery, demonstrated significantly unfavorable outcomes. Fifteen patients with persistent HPV 16/18 had the worst prognosis than the other types. Conclusion: Preoperative and postoperative HR-HPV genotype tests were used to predict the cumulative incidence of abnormal cytology and additional surgery. Particularly, patients with suspected persistent HPV type 16/18 infection are at a high recurrence risk.

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;6870(64):394–424. Erratum in: CA Cancer J Clin. 2020 Jul;70(4):313.
Nagase S, Ohta T, Takahashi F, Enomoto T; 2017 Committee on Gynecologic Oncology of the Japan Society of Obstetrics and Gynecology. Annual report of the committee on gynecologic oncology, the Japan Society of Obstetrics and Gynecology: annual patients report for 2015 and annual treatment report for 2010. J Obstet Gynaecol Res. 2019;45(2):289–98.
National Cancer Center Japan. Cancer statistics prediction [Internet]. Tokyo: National Cancer Center Japan; 2021. 2021 October 4. Available from: (accessed April 21, 2022).
Schiffman M, Castle PE, Jeronimo J, Rodriguez AC, Wacholder S. Human papillomavirus and cervical cancer. Lancet. 2007;370(9590):890–907.
Hampson IN, Oliver AW, Hampson L. Potential effects of human papillomavirus type substitution, superinfection exclusion and latency on the efficacy of the current L1 prophylactic vaccines. Viruses. 2020;13(1):22.
de Villiers EM. Cross-roads in the classification of papillomaviruses. Virology. 2013;445(1–2):2–10.
Cohen PA, Jhingran A, Oaknin A, Denny L. Cervical cancer. Lancet. 2019;393(10167):169–82.
Matsumoto K, Oki A, Furuta R, Maeda H, Yasugi T, Takatsuka N, et al. Predicting the progression of cervical precursor lesions by human papillomavirus genotyping: a prospective cohort study. Int J Cancer. 2011 Jun 15;128(12):2898–910.
Khan MJ, Castle PE, Lorincz AT, Wacholder S, Sherman M, Scott DR, et al. The elevated 10-year risk of cervical precancer and cancer in women with human papillomavirus (HPV) type 16 or 18 and the possible utility of type-specific HPV testing in clinical practice. J Natl Cancer Inst. 2005 Jul 20;97(14):1072–9.
Onuki M, Matsumoto K, Iwata T, Yamamoto K, Aoki Y, Maenohara S, et al. Human papillomavirus genotype contribution to cervical cancer and precancer: implications for screening and vaccination in Japan. Cancer Sci. 2020 Jul;111(7):2546–57.
Hammer A, Rositch A, Qeadan F, Gravitt PE, Blaakaer J. Age-specific prevalence of HPV 16/18 genotypes in cervical cancer: a systematic review and meta-analysis. Int J Cancer. 2016;138(12):2795–803.
Mayrand MH, Duarte-Franco E, Rodrigues I, Walter SD, Hanley J, Ferenczy A, et al. Human papillomavirus DNA versus Papanicolaou screening tests for cervical cancer. N Engl J Med. 2007 Oct 18;357(16):1579–88.
Koliopoulos G, Nyaga VN, Santesso N, Bryant A, Martin-Hirsch PP, Mustafa RA, et al. Cytology versus HPV testing for cervical cancer screening in the general population. Cochrane Database Syst Rev. 2017 Aug 10;8(8):CD008587.
Arbyn M, Sasieni P, Meijer CJLM, Clavel C, Koliopoulos G, Dillner J. Chapter 9: clinical applications of HPV testing: a summary of meta-analyses. Vaccine. 2006;24(Suppl 3):S78–89.
Naucler P, Ryd W, Törnberg S, Strand A, Wadell G, Elfgren K, et al. Human papillomavirus and Papanicolaou tests to screen for cervical cancer. N Engl J Med. 2007 Oct 18;357(16):1589–97.
Oishi T, Kigawa J, Iwanari O, Kasai T, Kurokawa T, Hamada M, et al. Is cytology/HPV co-testing for cervical cancer screening useful in Japan? Int J Gynaecol Obstet. 2022;158(1):187–93.
US Preventive Services Task Force; Curry SJ, Krist AH, Owens DK, Barry MJ, Caughey AB, et al. Screening for cervical cancer: US preventive services task force recommendation statement. JAMA. 2018 Aug 21;320(7):674–86.
Kurman RJ, Carcangiu ML, Herrington CS, Young RH. WHO classification of tumours of the female reproductive organs. Lyon: IARC press; 2014.
Arbyn M, Redman CWE, Verdoodt F, Kyrgiou M, Tzafetas M, Ghaem-Maghami S, et al. Incomplete excision of cervical precancer as a predictor of treatment failure: a systematic review and meta-analysis. Lancet Oncol. 2017 Dec;18(12):1665–79.
Costa S, De Simone P, Venturoli S, Cricca M, Zerbini ML, Musiani M, et al. Factors predicting human papillomavirus clearance in cervical intraepithelial neoplasia lesions treated by conization. Gynecol Oncol. 2003 Aug;90(2):358–65.
Kudoh A, Sato S, Itamochi H, Komatsu H, Nonaka M, Sato S, et al. Human papillomavirus type-specific persistence and reappearance after successful conization in patients with cervical intraepithelial neoplasia. Int J Clin Oncol. 2016 Jun;21(3):580–7.
Nayar R, Wilbur DC. The pap test and Bethesda 2014. Cancer Cytopathol. 2015 May;123(5):271–81.
Kanda Y. Investigation of the freely available easy-to-use software “EZR” for medical statistics. Bone Marrow Transplant. 2013;48(3):452–8.
Almog B, Gamzu R, Kuperminc MJ, Levin I, Fainaru O, Niv J, et al. Human papilloma virus testing in patient follow-up post cone biopsy due to high-grade cervical intraepithelial neoplasia. Gynecol Oncol. 2003 Mar;88(3):345–50.
Kang WD, Ju UC, Kim SM. A human papillomavirus (HPV)-16 or HPV-18 genotype is a reliable predictor of residual disease in a subsequent hysterectomy following a loop electrosurgical excision procedure for cervical intraepithelial neoplasia 3. J Gynecol Oncol. 2016;27(1):e2.
Friebe K, Klapdor R, Hillemanns P, Jentschke M. The value of partial HPV genotyping after conization of cervical dysplasias. Geburtshilfe Frauenheilkd. 2017;77(8):887–93.
Wu D, Zheng Y, Chen W, Guo C, Yu J, Chen G, et al. Prediction of residual/recurrent disease by HPV genotype after loop excision procedure for high-grade cervical intraepithelial neoplasia with negative margins. Aust N Z J Obstet Gynaecol. 2011 Apr;51(2):114–8.
Kamio M, Yanazume S, Togami S, Kobayashi H. Association between positive human papillomavirus status after conization and disease recurrence in patients with cervical intraepithelial neoplasia grade 3. J Obstet Gynaecol India. 2021;71(1):66–71.
Jones J, Saleem A, Rai N, Shylasree TS, Ashman S, Gregory K, et al. Human papillomavirus genotype testing combined with cytology as a “test of cure” post treatment: the importance of a persistent viral infection. J Clin Virol. 2011 Oct;52(2):88–92.
Kang WD, Oh MJ, Kim SM, Nam JH, Park CS, Choi HS. Significance of human papillomavirus genotyping with high-grade cervical intraepithelial neoplasia treated by a loop electrosurgical excision procedure. Am J Obstet Gynecol. 2010;203(1):72.e1–6.
Kreimer AR, Schiffman M, Herrero R, Hildesheim A, González P, Burk RD, et al. Long-term risk of recurrent cervical human papillomavirus infection and precancer and cancer following excisional treatment. Int J Cancer. 2012 Jul 1;131(1):211–8.
Rouzier R. Management of CIN1. J Gynecol Obstet Biol Reprod. 2008;37(Suppl 1):S114–120.
Kilic D, Guler T, Atigan A, Avsaroglu E, Karakaya YA, Kaleli I, et al. Predictors of Human papillomavirus (HPV) persistence after treatment of high grade cervical lesions; does cervical cytology have any prognostic value in primary HPV screening? Ann Diagn Pathol. 2020 Dec;49:151626.
Gargiulo F, De Francesco MA, Schreiber C, Ciravolo G, Salinaro F, Valloncini B, et al. Prevalence and distribution of single and multiple HPV infections in cytologically abnormal cervical samples from Italian women. Virus Res. 2007 May;125(2):176–82.
Stevens MP, Tabrizi SN, Quinn MA, Garland SM. Human papillomavirus genotype prevalence in cervical biopsies from women diagnosed with cervical intraepithelial neoplasia or cervical cancer in Melbourne, Australia. Int J Gynecol Cancer. 2006;16(3):1017–24.
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