Molecular-Epidemiological Study for 19 High and Medium-Risk HPV types in Bulgarian Patients

Author(s): Mariela Hristova Savova, Asen Kanev, Ivanka Dimova

Cervical cancer ranks as the 4th leading cause of female cancer and cancer deaths in the world. More than 99% of cervical cancer cases are due to HPV infection. Vaccination can significantly reduce the number of HPV-related cancers in the future. The next big step is to change the order of the tests, ie. cervical cells are first tested for HPV, and then analyzed under a microscope. The objective of our study was to define the incidence of 19 types of HPV in Bulgarian women attended for routine gynecologic examination, in order to obtain the molecular-epidemiological spectrum of this infection in the context of the actual preventive programs. We have used the medium-high risk PapillomaStrip kit, based on the principle of reverse hybridization, in samples of 151 Bulgarian women. We detected the total frequency of 44.4% for HPV infection and higher frequency in younger age group (<30 years – 47.5% and 30-40 years – 50%) compared to > 40 years old women (28%). The most frequent HPV types from our study were HPV 45 and 52 (10.6%), HPV 66 (8.6%) and HPV 31 (8%). In PAPI/II it was HPV52 (11.3%), followed by HPV45 (10.5%) and HPV66 (8.3%). In PAPIII the most common was HPV16 (44.4%), followed by HPV 45, 31, 66 and 59 (each of 22.2%). We emphasized on the high frequency of HPV45 in our study, which is reported as one of the most frequent types in cervical cancer. In conclusion, HPV genotyping provides information on the carriage of high-risk types and increased attention to these patients. This is a valuable information for planning preventive programs in regard to choosing diagnostic tests and vaccination. Our results revealed the wide spectrum of HPV infection in Bulgarian women, as about 70% of infected patients carry high-risk HPV 45, 52, 31, 16 and 18.

HPV Types, Molecular Epidemiology, HPV Vaccine

1. Boshart M., Gissmann L., Ikenberg H., Kleinheinz A., Scheurlen W., zur Hausen H. (1984) A new type of papillomavirus DNA, its presence in genital cancer and in cell lines derived from genital cancer EMBO J., 3 pp. 1151-1157
2. Bruni L, Barrionuevo-Rosas L, Albero G, Serrano B, Mena M, Gómez D, Muñoz J, Bosch FX, de Sanjosé S. (2017) ICO/IARC Information Centre on HPV and Cancer (HPV Information Centre). Human Papillomavirus and Related Diseases in the World. Summary Report.
3. Canfell K et al. (2017) Cervical screening with primary HPV testing or cytology in a population of women in which those aged 33 years or younger had previously been offered HPV vaccination: Results of the Compass pilot randomised trial. PLoS Med.
4. Chaturvedi AK, Engels EA, Pfeiffer RM, et al. (2011) Human papillomavirus and rising oropharyngeal cancer incidence in the United States. Journal of Clinical Oncology ; 29(32):4294–4301.
5. Dunne EF, Unger ER, Sternberg M, McQuillan G, Swan DC, Patel SS, Markowitz LE. (2007) Prevalence of HPV infection among females in the United States. JAMA ; Feb 28;297:813-9.
6. Dursun P, Ayhan A, Mutlu L, Çağlar M, Haberal A, Güngör T, Özat M, Özgü E, Onan A, Taşkiran C,et al. (2013) HPV types in Turkey: multicenter hospital based evaluation of 6388 patients in Turkish gynecologic oncology group centers. Turk Patoloji Derg.; 29:210-6.
7. Duvlis S, Plaseska-Karanfilska D, Bashevska N, Dimitrov G, Milanova E, Naumov J, Efremov GD (2001). A variant of human papillomavirus (HPV) type 66 is common among HPV-infected women from the Republic of Macedonia. Balkan Journal of Medical Genetics; 4:53-57.
8. Franco EL, Villa LL, Sobrinho JP, Prado JM, Rousseau MC, Désy M, Rohan TE. (1999) Epidemiology of acquisition and clearance of cervical human papillomavirus infection in women from a high-risk area for cervical cancer. J Infect Dis. 1 180(5):1415-23.
9. Georgiev Sasho Dissertation (2017): http://nt-cmb.mu-sofia.bg:8080/jspui/bitstream/10861/1397/1/Sasho_Georgiev-dis.pdf
10. Gillison ML, Chaturvedi AK, Lowy DR. (2008) HPV prophylactic vaccines and the potential prevention of noncervical cancers in both men and women. Cancer ; 113(10 Suppl):3036-3046.
11. Grozdanov P. Dissertation (2011): http://www.microbio.bas.bg/IMB%20web%20page/pzrasrb/Doctor/Peshko/avtoreferatpdf.pdf
12. HPV immunisation uptake statistics. Health Protection Surveillance Centre, Dublin; (2018) http://www.hpsc.ie/a-z/vaccinepreventable/vaccination/immunisationuptakestatistics/hpvimmunisationuptakestatistics/
13. Huh WK, Joura EA, Giuliano AR, et al. (2017) Final efficacy, immunogenicity, and safety analyses of a nine-valent human papillomavirus vaccine in women aged 16-26 years: a randomised, double-blind trial. Lancet ; 390(10108):2143-2159.
14. Kjaer SK, Nygård M, Dillner J, et al. (2018) A 12-year follow-up on the long-term effectiveness of the quadrivalent human papillomavirus vaccine in 4 Nordic countries. Clinical Infectious Diseases ; 66(3):339-345.
15. Koutsky LA, Ault KA, Wheeler CM, et al. (2002) A controlled trial of a human papillomavirus type 16 vaccine. New England Journal of Medicine ; 347(21):1645-1651.
16. Kovacevic G, Nikolic N, Jovanovic-Galovic A, Hrnjakovic-Cvjetkovic I, Vuleta D, Patic A, Radovanov J, Milosevic V. (2016) Frequency of twelve carcinogenic human papilloma virus types among women from the South Backaregion, Vojvodina, Serbia. Turk J Med Sci. ; 46:97-104.
17. Kovachev S, Slavov V, Slavova K. (2013) Prevalence of human papillomavirus infection in women in some cities and regions of Bulgaria. J Med Virol. Sep;85(9):1577-84
18. Kovachev S, Slavov V. (2018) Prevalence of human papillomavirus infection in women in Bulgaria: A 2017 update. J Med Virol. Jun;90(6):1142-1149
19. Lew JB et al. (2017) Primary HPV testing versus cytology-based cervical screening in women in Australia vaccinated for HPV and unvaccinated: effectiveness and economic assessment for the National CervicalScreening Program. Lancet Public Health.
20. Munoz N, Castellsague X, de Gonzalez AB, Gissmann L. (2006) Chapter 1: HPV in the etiology of human cancer. Vaccine; 24:1–10.
21. Naud PS, Roteli-Martins CM, De Carvalho NS, et al. (2014) Sustained efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine: Final analysis of a long-term follow-up study up to 9.4 years post-vaccination. Human Vaccines and Immunotherapeutics ; 10(8):2147-2162.
22. Safaeian M, Solomon D, Castle PE. (2007) Cervical cancer prevention--cervical screening: science in evolution. Obstet Gynecol Clin North Am.;34(4):739-60
23. Stamataki P, Papazafiropoulou A, Elefsiniotis I, Giannakopoulou M, Brokalaki H, Apostolopoulou E, Sarafis P, Saroglou G. (2010) Prevalence of HPV infection among Greek women attending a gynecological outpatient clinic. BMC Infect Dis. ;10:27.
24. Tota JE et al. (2017) Introduction of molecular HPV testing as the primary technology in cervical cancer screening: Acting on evidence to change the current paradigm. Prev Med.
25. Ursu RG, Onofriescu M, Nemescu D, Iancu LS. (2011) HPV prevalence and type distribution in women with or without cervical lesions in the Northeast region of Romania. Virol J. ; 8:558.
26. Woodman CB, Collins S, Winter H, Bailey A, Ellis J, Prior P, Yates M, Rollason TP, Young LS. (2001) Natural history of cervical human papillomavirus infection in young women: a longitudinal cohort study.Lancet.;357(9271):1831-6.