Impact of the human papillomavirus vaccination on patients who underwent conization for high-grade cervical intraepithelial neoplasia
1Department of Obstetrics and Gynecology, Santa Lucía University Hospital, Cartagena. Program of Doctorate in Health Sciences, Catholic University of Murcia (UCAM), Murcia
2Department of Obstetrics and Gynecology, Virgen de la Arrixaca University Hospital, Murcia. Catholic University of Murcia (UCAM), Murcia
3Applied Statistical Methods in Medical Research Group, Catholic University of Murcia (UCAM), Murcia
4Applied Statistical Methods in Medical Research Group, Catholic University of Murcia (UCAM), Murcia (Spain). Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London (United Kingdom)
5Department of Obstetrics and Gynecology, Santa Lucía University Hospital, Cartagena, Murcia
6Department of Biochemestry, Santa Lucía University Hospital, Cartagena, Murcia
7Department of Obstetrics and Gynecology, Santa Lucía University Hospital, Cartagena. Catholic University of Murcia (UCAM), Murcia (Spain)
DOI: 10.12892/ejgo4628.2019 Vol.40,Issue 3,June 2019 pp.402-407
Published: 10 June 2019
Objectives: To test whether the human papillomavirus (HPV) vaccination in patients undergoing loop diathermy conization (LEEP) for high-grade intraepithelial neoplasia (CIN 2-3) is effective in preventing recurrence of CIN 2-3 in our area. Materials and Methods: A retrospective review was conducted on 242 patients undergoing LEEP for CIN 2-3 and 42.6% received the HPV vaccine (bivalent or tetravalent) immediately before or after conization. Follow up was conducted at 3, 6, 12, 18, and 24 months to detect CIN 2-3 recurrence. Results: Regardless of the HPV type, 27 (11.1%) patients developed CIN 2-3 recurrence during post-LEEP follow up. Of the 70 vaccinated with bivalent vaccine, two (2.8%) showed recurrence, of the 33 vaccinated with tetravalent vaccine, three (9%), and of the 139 unvaccinated 61 (43.9%) developed recurrence. Of the patients infected with HPV genotypes 16/18, in the non-vaccinated group, 15 (21.7%) patients had recurrence, whereas in the vaccinated group, three (5.9%) were diagnosed with recurrence (p < 0/05). The multivariate logistic regression analysis showed that the vaccination acted as a protective factor for CIN 2-3 recurrence (OR: 0.360 (95% CI: 0.125-1.000; p < 0.05). However, neither the type of vaccine nor the time of vaccination showed a significant association with the onset of recurrence. Conclusions: The HPV vaccine appears to be a recommendable preventative strategy in reducing the risk of recurrent disease for patients treated for CIN 2-3.
Human papillomavirus; Vaccine; Cervical intraepithelial neoplasia; Recurrent disease; Conization; LEEP
P. Ortega-Quiñonero,M. Remezal-Solano,M.C. Carazo-Díaz,D. Prieto-Merino,M.I. Urbano-Reyes,L. García de Guadiana-Romualdo,J.P. Martínez-Cendán. Impact of the human papillomavirus vaccination on patients who underwent conization for high-grade cervical intraepithelial neoplasia. European Journal of Gynaecological Oncology. 2019. 40(3);402-407.
 Ferlay J., Shin H.R., Bray F., Forman D., Mathers C., Parkin D.M.: “Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008”. Int. J. Cancer, 2010, 127, 2893.
 Cox J.T.: “Epidemiology of cervical intraepithelial neoplasia: the role of human papillomavirus”. Baillieres Clin. Obstet. Gynecol., 1995, 9, 1.
 Konno R., Shin H.R., Kim Y.T., Song Y.S., Sasagawa T., Inoue M., et al.: “Human papillomavirus infection and cervical cancer prevention in Japan and Korea”. Vaccine, 2008, 26, 30.
 Insinga R.P., Glass A.G., Rush B.B.: “Diagnoses and outcomes in cervical cancer screening: a population based study”. Am. J. Obstet. Gynecol., 2004, 191, 105.
 Wright T.C. Jr., Massad L.S., Dunton C.J., Spitzer M., Wilkinson E.J., Solomon D., et al.: “2006 consensus guidelines for the management of women with cervical intraepithelial neoplasia or adenocarcinoma in situ”. Am. J. Obstet. Gynecol., 2007, 197, 340.
 Soutter W.P., Sasieni P., Panoskaltsis T.: “Long-term risk of invasive cervical cancer after treatment of squamous cervical intraepithelial neoplasia”. Int. J. Cancer, 2006, 118, 2048.
 Martin-Hirsch P.P., Paraskevaidis E., Bryant A., Dickinson H.O.: “Surgery for cervical intraepithelial neoplasia”. Cochrane Database Syst. Rev., 2013, 12, CD001318.
 Paavonen J., Jenkins D., Bosch F.X., Naud P., Salmeron J., Wheeler C.M., et al.: “Efficacy of a prophylactic adjuvanted bivalent L1 virus-like-particle vaccine against infection with Human papillomavirus types 16 and 18 in young women: an interim analysis of a phase III double-blind, randomised controlled trial”. Lancet, 2007, 369, 2161.
 Paavonen J., Naud P., Salmeron J., Wheeler C.M., Chow S.N., Apter D., et al.: “Efficacy of Human papillomavirus (HPV)-16/18 AS04- adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a doubleblind, randomised study in young women”. Lancet, 2009, 374, 301.
 FUTURE II Study Group: “Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions”. N. Engl. J. Med., 2007, 356, 1915.
 Ault K.: “Effect of prophylactic human papillomavirus L1 virus-likeparticle vaccine on risk of cervical intraepithelial neoplasia grade 2, grade 3 and adenocarcinoma in situ: a combined analysis of four randomised clinical trials”. Lancet, 2007, 369, 1861.
 Garland S., on behalf of the HPV PATRICIA Study Group: “Efficacy of the HPV-16/18 AS04-adjuvanted vaccine against vulvar/vaginal intraepithelial neoplasia”. In: 27th International Papilloma Conference and Workshop. Berlin: 2011. [Cited 12 November 2017]. Available at: http://ipvsoc.org/event/27th-annualinternational-papillomavirus-conference-clinical-workshops/
 Joura E.A., Giuliano A.R., Iversen O.E., Bouchard C., Mao C., Mehlsen J., et al.: “A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women”. N. Engl. J. Med., 2015, 372, 711.
 Skinner S.R., Szarewski A., Romanowski B., Garland S.M., Lazcano-Ponce E.5., Salmerón J., et al.: “Efficacy, safety, and immunogenicity of the human papillomavirus 16/18 AS04-adjuvanted vaccine in women older than 25 years: 4-year interim follow-up of the phase 3, double-blind, randomised controlled VIVIANE study”. Lancet, 2014, 384, 2213.
 Joura E.A., Garland S.M., Paavonen J., Ferris D.G., Perez G., Ault K.A.: “Effect of the human papillomavirus (HPV) quadrivalent vaccine in a subgroup of women with cervical and vulvar disease: retrospective pooled analysis of trial data”. BMJ, 2012, 344, 1401.
 Kang W.D., Choi H.S., Kim S.M.: “Is vaccination with quadrivalent HPV vaccine after loop electrosurgical excision procedure effective in preventing recurrence in patients with high-grade cervical intraepithelial neoplasia (CIN2–3)?” Obstet. Gynecol., 2013, 130, 264.
 Prendiville W., Cullimore J., Norman S.: “Large loop excision of the transforming zone (LLETZ): a new method of management for women with cervical intraepithelial neoplasia”. Br. J. Obstet. Gynecol., 1989, 96, 1054.
 Lindeque B.G.: “Management of cervical premalignant lesions”. Best Pract. Res. Clin. Obstet. Gynecol., 2005, 19, 545.
 Fogle R.H., Spann C.O., Easley K.A., Basil J.B.: “Predictors of cervical dysplasia after the loop electrosurgical excision procedure in an inner-city population”. J. Reprod. Med., 2004, 49, 481.
 Gardeil F., Barry-Walsh C., Prendiville W., Clinch J., Turner M.J.: “Persistent intraepithelial neoplasia after excision for cervical intraepithelial neoplasia grade III”. Obstet. Gynecol., 1997, 89, 419.
 Dietrich C.S., Yancey M., Miyazawa K., Williams D., Farley J.: “Risk factors for early cytological abnormalities after loop electrosurgical excision procedure”. Obstet. Gynecol., 2002, 99, 188.
 Livasy C.A., Moore D.T., Van Le L.: “The clinical significance of a negative loop electrosurgical cone biopsy for high-grade dysplasia”. Obstet. Gynecol., 2004, 104, 250.
 Carter J., Sim J., Land R., Dalrymple C., Abdel-Hadi M., Pather S.: “Recurrence after treatment for high-grade dysplasia: should we modify our post-treatment surveillance protocols?” Aust. N. Z. J. Obstet. Gynecol., 2006, 46, 360.
 Alonso I., Torne A., Puig-Tintore L.M., Esteve R., Quinto L., Campo E., et al.: “Pre-and post-conization high-risk HPV testing predicts residual/recurrent disease in patients treated for CIN 2-3”. Gynecol. Oncol., 2006, 103, 631.
 Jakobsson M., Gissler M., Paavonen J., Tapper A.M.: “Loop electrosurgical excision procedure and the risk for preterm birth”. Obstet. Gynecol., 2009, 114, 504.
 Robinson W.R., Lund E.D., Adams J.: “The predictive value of LEEP specimen margin status for residual/recurrent cervical intra- epithelial neoplasia”. Int. J. Gynecol. Cancer, 1998, 8, 109.
 Skinner E.N., Gehrig P.A., Van Le L.: “High-grade squamous intraepithelial lesions: abbreviating posttreatment surveillance”. Obstet. Gynecol., 2004, 103, 488.
 Verguts J., Bronselaer B., Donders G., Arbyn M., Van Eldere J., Drijkoningen M., Poppe W.: “Prediction of recurrence after treatment for high-grade cervical intraepithelial neoplasia: the role of human papillomavirus testing and age at conization”. BJOG, 2006, 113, 1303.
 Elfgren K., Jacobs M., Walboomers J.M., Meijer C.J., Dillner J.: “Rate of human papillomavirus clearance after treatment of cervical intraepithelial neoplasia”. Obstet. Gynecol., 2002, 100, 965.
 Paraskevaidis E., Koliopoulos G., Alamanos Y., Malamou-Mitsi V., Lolis E.D., Kitchener H.C.: “Human papillomavirus testing and the outcome of treatment for cervical intraepithelial neoplasia”. Obstet. Gynecol., 2001, 98, 833.
 Chua K.L., Hjerpe A.: “Human papillomavirus analysis as a prognostic marker following conization of the cervix uteri”. Gynecol. Oncol., 1997, 66, 101.
 Kocken M., Uijterwaal M.H., de Vries A.L., Berkhof J., Ket J.C., Helmerhorst T.J., et al.: “High- risk human papillomavirus testing versus cytology in predicting post-treatment disease in women treated for high-grade cervical disease: a systematic review and meta-analysis”. Gynecol. Oncol., 2012, 125, 500.
 KangW.D., Oh M.J., Kim S.M., Nam J.H., Park C.S., Choi H.S.:“Significance of human papillo- mavirus genotyping with high-grade cervical intraepithelial neoplasia treated by a loop electrosurgical excision procedure”. Am. J. Obstet. Gynecol., 2010, 203, 72.
 Haupt R.M., Wheeler C.M., Brown D.R., Garland S.M., Ferris D.G., Paavonen J.A., et al.: “Impact of an HPV6/11/16/18 L1 virus-like particle vaccine on progression to cervical intraepithelial neoplasia in seropositive women with HPV16/18 infection”. Int. J. Cancer, 2011, 129, 2632.
 Pérez- Martin J., Navarro-Alonso J.A., Cayuela-Fuentes J., BernalGonzález P.: “Vaccination Program against HPV in Women with Excisional Treatment Due to Preneoplasic Cervical Lesions in the Region of Murcia: Results of the First Year”. Clin. Res. Infect. Dis., 2016, 3, 1031.
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