Skip to main content
Top
Published in: BMC Infectious Diseases 1/2014

Open Access 01-12-2014 | Research article

Human papillomavirus infection in Bhutan at the moment of implementation of a national HPV vaccination programme

Authors: Ugyen Tshomo, Silvia Franceschi, Dorji Dorji, Iacopo Baussano, Vanessa Tenet, Peter JF Snijders, Chris JLM Meijer, Maaike CG Bleeker, Tarik Gheit, Massimo Tommasino, Gary M Clifford

Published in: BMC Infectious Diseases | Issue 1/2014

Login to get access

Abstract

Background

Cervical cancer is the most common female cancer in Bhutan, the first low/middle-income country to implement a national human papillomavirus (HPV) vaccination programme.

Methods

To provide a robust baseline for future evaluations of vaccine effectiveness, cervical cell specimens were obtained from 2,505 women aged 18–69 years from the general population, and biopsies from 211 cervical intraepithelial neoplasia grade 3 (CIN3) and 112 invasive cervical cancer (ICC) cases. Samples were tested for HPV using GP5+/6+ PCR.

Results

Among the general population, HPV prevalence was 26%, being highest (33%) in women ≤24 years, but remaining above 15% in all age-groups. Determinants of HPV included age, marital status, and number of sexual partners. Among the eight percent with cytological abnormalities, 24 CIN3 and 4 ICC were histologically confirmed. Even after additional testing with a sensitive E7 PCR, no infections with vaccine-targeted HPV types were detected in the few vaccinated women (n = 34) compared to 6% prevalence in unvaccinated women of similar age (p = 0 · 215).

Conclusion

Based upon type-specific prevalence among biopsies, at least 70% of ICC in Bhutan are theoretically preventable by HPV16/18 vaccination, but screening programmes should be expanded among older women, who have an important underlying burden of CIN3 and ICC.
Appendix
Available only for authorised users
Literature
1.
go back to reference Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F: GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worlwide: IARC CancerBase No. 11 [Internet]. 2013, Lyon, France: International Agency for Research on Cancer Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F: GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worlwide: IARC CancerBase No. 11 [Internet]. 2013, Lyon, France: International Agency for Research on Cancer
2.
go back to reference World Cancer Report 2014. Edited by: Steward BW, Wild CP. 2014, Lyon, France: International Agency for Research on Cancer World Cancer Report 2014. Edited by: Steward BW, Wild CP. 2014, Lyon, France: International Agency for Research on Cancer
3.
go back to reference Clifford GM, Gallus S, Herrero R, Muñoz N, Snijders PJ, Vaccarella S, Anh PT, Ferreccio C, Hieu NT, Matos E, Molano M, Rajkumar R, Ronco G, de Sanjose S, Shin HR, Sukvirach S, Thomas JO, Tunsakul S, Meijer CJ, Franceschi S, and the IARC HPV Prevalence Surveys Study Group: Worldwide distribution of human papillomavirus types in cytologically normal women in the International Agency for Research on Cancer HPV prevalence surveys: a pooled analysis. Lancet. 2005, 366: 991-998. 10.1016/S0140-6736(05)67069-9.CrossRefPubMed Clifford GM, Gallus S, Herrero R, Muñoz N, Snijders PJ, Vaccarella S, Anh PT, Ferreccio C, Hieu NT, Matos E, Molano M, Rajkumar R, Ronco G, de Sanjose S, Shin HR, Sukvirach S, Thomas JO, Tunsakul S, Meijer CJ, Franceschi S, and the IARC HPV Prevalence Surveys Study Group: Worldwide distribution of human papillomavirus types in cytologically normal women in the International Agency for Research on Cancer HPV prevalence surveys: a pooled analysis. Lancet. 2005, 366: 991-998. 10.1016/S0140-6736(05)67069-9.CrossRefPubMed
4.
go back to reference Solomon D, Davey D, Kurman R, Moriarty A, O’Connor D, Prey M, Raab S, Sherman M, Wilbur D, Wright T, Young N: The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA. 2002, 287: 2114-2119. 10.1001/jama.287.16.2114.CrossRefPubMed Solomon D, Davey D, Kurman R, Moriarty A, O’Connor D, Prey M, Raab S, Sherman M, Wilbur D, Wright T, Young N: The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA. 2002, 287: 2114-2119. 10.1001/jama.287.16.2114.CrossRefPubMed
5.
go back to reference Roda Husman AM, Snijders PJ, Stel HV, van den Brule AJ, Meijer CJ, Walboomers JM: Processing of long-stored archival cervical smears for human papillomavirus detection by the polymerase chain reaction. Br J Cancer. 1995, 72: 412-417. 10.1038/bjc.1995.347.CrossRefPubMedPubMedCentral Roda Husman AM, Snijders PJ, Stel HV, van den Brule AJ, Meijer CJ, Walboomers JM: Processing of long-stored archival cervical smears for human papillomavirus detection by the polymerase chain reaction. Br J Cancer. 1995, 72: 412-417. 10.1038/bjc.1995.347.CrossRefPubMedPubMedCentral
6.
go back to reference Jacobs MV, Walboomers JM, Snijders PJ, Voorhorst FJ, Verheijen RH, Fransen-Daalmeijer N, Meijer CJ: Distribution of 37 mucosotropic HPV types in women with cytologically normal cervical smears: the age-related patterns for high-risk and low-risk types. Int J Cancer. 2000, 87: 221-227. 10.1002/1097-0215(20000715)87:2<221::AID-IJC11>3.0.CO;2-2.CrossRefPubMed Jacobs MV, Walboomers JM, Snijders PJ, Voorhorst FJ, Verheijen RH, Fransen-Daalmeijer N, Meijer CJ: Distribution of 37 mucosotropic HPV types in women with cytologically normal cervical smears: the age-related patterns for high-risk and low-risk types. Int J Cancer. 2000, 87: 221-227. 10.1002/1097-0215(20000715)87:2<221::AID-IJC11>3.0.CO;2-2.CrossRefPubMed
7.
go back to reference van den Brule AJ, Pol R, Fransen-Daalmeijer N, Schouls LM, Meijer CJ, Snijders PJ: GP5+/6+ PCR followed by reverse line blot analysis enables rapid and high-throughput identification of human papillomavirus genotypes. J Clin Microbiol. 2002, 40: 779-787. 10.1128/JCM.40.3.779-787.2002.CrossRefPubMed van den Brule AJ, Pol R, Fransen-Daalmeijer N, Schouls LM, Meijer CJ, Snijders PJ: GP5+/6+ PCR followed by reverse line blot analysis enables rapid and high-throughput identification of human papillomavirus genotypes. J Clin Microbiol. 2002, 40: 779-787. 10.1128/JCM.40.3.779-787.2002.CrossRefPubMed
8.
go back to reference IARC: Monographs on the Evaluation of Carcinogenic Risks to Humans Volume 90: Human Papillomaviruses [90]. 2007, Lyon: International Agency for Research on Cancer. Monographs on the Evaluation of carcinogenic Risk to Humans, 1-670. IARC: Monographs on the Evaluation of Carcinogenic Risks to Humans Volume 90: Human Papillomaviruses [90]. 2007, Lyon: International Agency for Research on Cancer. Monographs on the Evaluation of carcinogenic Risk to Humans, 1-670.
9.
go back to reference Gheit T, Tommasino M: Detection of high-risk mucosal human papillomavirus DNA in human specimens by a novel and sensitive multiplex PCR method combined with DNA microarray. Methods Mol Biol. 2011, 665: 195-212.CrossRefPubMed Gheit T, Tommasino M: Detection of high-risk mucosal human papillomavirus DNA in human specimens by a novel and sensitive multiplex PCR method combined with DNA microarray. Methods Mol Biol. 2011, 665: 195-212.CrossRefPubMed
10.
11.
go back to reference Gheit T, Landi S, Gemignani F, Snijders PJ, Vaccarella S, Franceschi S, Canzian F, Tommasino M: Development of a sensitive and specific assay combining multiplex PCR and DNA microarray primer extension to detect high-risk mucosal human papillomavirus types. J Clin Microbiol. 2006, 44: 2025-2031. 10.1128/JCM.02305-05.CrossRefPubMedPubMedCentral Gheit T, Landi S, Gemignani F, Snijders PJ, Vaccarella S, Franceschi S, Canzian F, Tommasino M: Development of a sensitive and specific assay combining multiplex PCR and DNA microarray primer extension to detect high-risk mucosal human papillomavirus types. J Clin Microbiol. 2006, 44: 2025-2031. 10.1128/JCM.02305-05.CrossRefPubMedPubMedCentral
12.
go back to reference Keita N, Clifford GM, Koulibaly M, Douno K, Kabba I, Haba M, Sylla BS, van Kemenade FJ, Snijders PJ, Meijer CJ, Franceschi S: HPV infection in women with and without cervical cancer in Conakry, Guinea. Br J Cancer. 2009, 101: 202-208. 10.1038/sj.bjc.6605140.CrossRefPubMedPubMedCentral Keita N, Clifford GM, Koulibaly M, Douno K, Kabba I, Haba M, Sylla BS, van Kemenade FJ, Snijders PJ, Meijer CJ, Franceschi S: HPV infection in women with and without cervical cancer in Conakry, Guinea. Br J Cancer. 2009, 101: 202-208. 10.1038/sj.bjc.6605140.CrossRefPubMedPubMedCentral
13.
go back to reference Dondog B, Clifford GM, Vaccarella S, Waterboer T, Unurjargal D, Avirmed D, Enkhtuya S, Kommoss F, Wentzensen N, Snijders PJ, Meijer CJ, Franceschi S, Pawlita M: Human papillomavirus infection in Ulaanbaatar, Mongolia: a population-based study. Cancer Epidemiol Biomarkers Prev. 2008, 17: 1731-1738. 10.1158/1055-9965.EPI-07-2796.CrossRefPubMed Dondog B, Clifford GM, Vaccarella S, Waterboer T, Unurjargal D, Avirmed D, Enkhtuya S, Kommoss F, Wentzensen N, Snijders PJ, Meijer CJ, Franceschi S, Pawlita M: Human papillomavirus infection in Ulaanbaatar, Mongolia: a population-based study. Cancer Epidemiol Biomarkers Prev. 2008, 17: 1731-1738. 10.1158/1055-9965.EPI-07-2796.CrossRefPubMed
14.
go back to reference Thomas JO, Herrero R, Omigbodun AA, Ojemakinde K, Ajayi IO, Fawole A, Oladepo O, Smith JS, Arslan A, Muñoz N, Snijders PJ, Meijer CJ, Franceschi S: Prevalence of papillomavirus infection in women in Ibadan, Nigeria: a population-based study. Br J Cancer. 2004, 90: 638-645. 10.1038/sj.bjc.6601515.CrossRefPubMedPubMedCentral Thomas JO, Herrero R, Omigbodun AA, Ojemakinde K, Ajayi IO, Fawole A, Oladepo O, Smith JS, Arslan A, Muñoz N, Snijders PJ, Meijer CJ, Franceschi S: Prevalence of papillomavirus infection in women in Ibadan, Nigeria: a population-based study. Br J Cancer. 2004, 90: 638-645. 10.1038/sj.bjc.6601515.CrossRefPubMedPubMedCentral
15.
go back to reference Aruhuri B, Tarivonda L, Tenet V, Sinha R, Snijders PJ, Clifford G, Pang J, McAdam M, Meijer CJ, Frazer IH, Franceschi S: Prevalence of Cervical Human Papillomavirus (HPV) Infection in Vanuatu. Cancer Prev Res (Phila). 2012, 5: 746-753. 10.1158/1940-6207.CAPR-11-0515.CrossRef Aruhuri B, Tarivonda L, Tenet V, Sinha R, Snijders PJ, Clifford G, Pang J, McAdam M, Meijer CJ, Frazer IH, Franceschi S: Prevalence of Cervical Human Papillomavirus (HPV) Infection in Vanuatu. Cancer Prev Res (Phila). 2012, 5: 746-753. 10.1158/1940-6207.CAPR-11-0515.CrossRef
16.
go back to reference Franceschi S, Rajkumar R, Snijders PJF, Arslan A, Mahé C, Plummer M, Sankaranarayanan R, Cherian J, Meijer CJLM, Weiderpass E: Papillomavirus infection in rural women in southern India. Br J Cancer. 2005, 92: 601-606.CrossRefPubMedPubMedCentral Franceschi S, Rajkumar R, Snijders PJF, Arslan A, Mahé C, Plummer M, Sankaranarayanan R, Cherian J, Meijer CJLM, Weiderpass E: Papillomavirus infection in rural women in southern India. Br J Cancer. 2005, 92: 601-606.CrossRefPubMedPubMedCentral
17.
go back to reference Dai M, Bao YP, Li N, Clifford GM, Vaccarella S, Snijders PJF, Huang RD, Sun LX, Meijer CJLM, Qiao YL, Franceschi S: Human papillomavirus infection in Shanxi Province, People’s Republic of China: a population-based study. Br J Cancer. 2006, 95: 96-101. 10.1038/sj.bjc.6603208.CrossRefPubMedPubMedCentral Dai M, Bao YP, Li N, Clifford GM, Vaccarella S, Snijders PJF, Huang RD, Sun LX, Meijer CJLM, Qiao YL, Franceschi S: Human papillomavirus infection in Shanxi Province, People’s Republic of China: a population-based study. Br J Cancer. 2006, 95: 96-101. 10.1038/sj.bjc.6603208.CrossRefPubMedPubMedCentral
18.
go back to reference Wu RF, Dai M, Qiao YL, Clifford GM, Liu ZH, Arslan A, Li N, Shi JF, Snijders PJ, Meijer CJ, Franceschi S: Human papillomavirus infection in women in Shenzhen City, People’s Republic of China, a population typical of recent Chinese urbanisation. Int J Cancer. 2007, 121: 1306-1311. 10.1002/ijc.22726.CrossRefPubMed Wu RF, Dai M, Qiao YL, Clifford GM, Liu ZH, Arslan A, Li N, Shi JF, Snijders PJ, Meijer CJ, Franceschi S: Human papillomavirus infection in women in Shenzhen City, People’s Republic of China, a population typical of recent Chinese urbanisation. Int J Cancer. 2007, 121: 1306-1311. 10.1002/ijc.22726.CrossRefPubMed
19.
go back to reference Li N, Franceschi S, Howell-Jones R, Snijders PJ, Clifford GM: Human papillomavirus type distribution in 30,848 invasive cervical cancers worldwide: Variation by geographical region, histological type and year of publication. Int J Cancer. 2011, 128: 927-935. 10.1002/ijc.25396.CrossRefPubMed Li N, Franceschi S, Howell-Jones R, Snijders PJ, Clifford GM: Human papillomavirus type distribution in 30,848 invasive cervical cancers worldwide: Variation by geographical region, histological type and year of publication. Int J Cancer. 2011, 128: 927-935. 10.1002/ijc.25396.CrossRefPubMed
20.
go back to reference Sherpa AT, Clifford GM, Vaccarella S, Shrestha S, Nygård M, Karki BS, Snijders PJ, Meijer CJ, Franceschi S: Human papillomavirus infection in women with and without cervical cancer in Nepal. Cancer Causes Control. 2010, 21: 323-330. 10.1007/s10552-009-9467-z.CrossRefPubMed Sherpa AT, Clifford GM, Vaccarella S, Shrestha S, Nygård M, Karki BS, Snijders PJ, Meijer CJ, Franceschi S: Human papillomavirus infection in women with and without cervical cancer in Nepal. Cancer Causes Control. 2010, 21: 323-330. 10.1007/s10552-009-9467-z.CrossRefPubMed
21.
go back to reference Maucort-Boulch D, Franceschi S, Plummer M: International correlation between human papillomavirus prevalence and cervical cancer incidence. Cancer Epidemiol Biomarkers Prev. 2008, 17: 717-720. 10.1158/1055-9965.EPI-07-2691.CrossRefPubMed Maucort-Boulch D, Franceschi S, Plummer M: International correlation between human papillomavirus prevalence and cervical cancer incidence. Cancer Epidemiol Biomarkers Prev. 2008, 17: 717-720. 10.1158/1055-9965.EPI-07-2691.CrossRefPubMed
22.
go back to reference Guan P, Howell-Jones R, Li N, Bruni L, de Sanjose S, Franceschi S, Clifford GM: Human papillomavirus types in 115,789 HPV-positive women: a meta-analysis from cervical infection to cancer. Int J Cancer. 2012, 131: 2349-2359. 10.1002/ijc.27485.CrossRefPubMed Guan P, Howell-Jones R, Li N, Bruni L, de Sanjose S, Franceschi S, Clifford GM: Human papillomavirus types in 115,789 HPV-positive women: a meta-analysis from cervical infection to cancer. Int J Cancer. 2012, 131: 2349-2359. 10.1002/ijc.27485.CrossRefPubMed
23.
go back to reference Vaccarella S, Herrero R, Dai M, Snijders PJ, Meijer CJ, Thomas JO, Hoang Anh PT, Ferreccio C, Matos E, Posso H, de Sanjose S, Shin HR, Sukvirach S, Lazcano-Ponce E, Ronco G, Rajkumar R, Qiao YL, Muñoz N, Franceschi S: Reproductive factors, oral contraceptive use, and human papillomavirus infection: pooled analysis of the IARC HPV prevalence surveys. Cancer Epidemiol Biomarkers Prev. 2006, 15: 2148-2153. 10.1158/1055-9965.EPI-06-0556.CrossRefPubMed Vaccarella S, Herrero R, Dai M, Snijders PJ, Meijer CJ, Thomas JO, Hoang Anh PT, Ferreccio C, Matos E, Posso H, de Sanjose S, Shin HR, Sukvirach S, Lazcano-Ponce E, Ronco G, Rajkumar R, Qiao YL, Muñoz N, Franceschi S: Reproductive factors, oral contraceptive use, and human papillomavirus infection: pooled analysis of the IARC HPV prevalence surveys. Cancer Epidemiol Biomarkers Prev. 2006, 15: 2148-2153. 10.1158/1055-9965.EPI-06-0556.CrossRefPubMed
24.
go back to reference Vaccarella S, Franceschi S, Herrero R, Muñoz N, Snijders PJF, Clifford GM, Smith JS, Lazcano-Ponce E, Sukvirach S, Shin HR, de Sanjose S, Molano M, Matos E, Ferreccio C, Anh PTH, Thomas JO, Meijer CJLM, and the IARC HPV Prevalence Surveys Study Group: Sexual behavior, condom use and HPV: pooled analysis of the International Agency for Research on Cancer HPV Prevalence Surveys. Cancer Epidemiol Biomarkers Prev. 2006, 15: 326-333. 10.1158/1055-9965.EPI-05-0577.CrossRefPubMed Vaccarella S, Franceschi S, Herrero R, Muñoz N, Snijders PJF, Clifford GM, Smith JS, Lazcano-Ponce E, Sukvirach S, Shin HR, de Sanjose S, Molano M, Matos E, Ferreccio C, Anh PTH, Thomas JO, Meijer CJLM, and the IARC HPV Prevalence Surveys Study Group: Sexual behavior, condom use and HPV: pooled analysis of the International Agency for Research on Cancer HPV Prevalence Surveys. Cancer Epidemiol Biomarkers Prev. 2006, 15: 326-333. 10.1158/1055-9965.EPI-05-0577.CrossRefPubMed
Metadata
Title
Human papillomavirus infection in Bhutan at the moment of implementation of a national HPV vaccination programme
Authors
Ugyen Tshomo
Silvia Franceschi
Dorji Dorji
Iacopo Baussano
Vanessa Tenet
Peter JF Snijders
Chris JLM Meijer
Maaike CG Bleeker
Tarik Gheit
Massimo Tommasino
Gary M Clifford
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2014
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/1471-2334-14-408

Other articles of this Issue 1/2014

BMC Infectious Diseases 1/2014 Go to the issue