- Email: [email protected]
High-risk HPV infection among the tribal and non-tribal women of the Andaman and Nicobar Islands, India
p u b l i c h e a l t h 1 2 6 ( 2 0 1 2 ) 6 7 e6 9
Available online at www.sciencedirect.com
Public Health journal homepage: www.elsevier.com/puhe
Short Communication
High-risk HPV infection among the tribal and non-tribal women of the Andaman and Nicobar Islands, India R. Parvez a, S. Hedau b, D. Bhattacharya a, H. Bhattacharjee a, N. Muruganandam a, B.C. Das b, M.K. Saha c, A.P. Sugunan a, P. Vijayachari a,* a
Regional Medical Research Centre (ICMR), WHO Collaborating Centre for Diagnosis, Research, Reference and Training in Leptospirosis, Post Bag No. 13, Dollygunj, Port Blair 744101, Andaman and Nicobar Islands, India b Institute of Cytology and Preventive Oncology, I-7, Sectore39, Noida 201301, India c G.B. Pant Hospital, Port Blair 744101, Andaman and Nicobar Islands, India
article info Article history: Received 8 April 2010 Received in revised form 18 July 2011 Accepted 21 September 2011 Available online 29 November 2011
Papovaviruses have long been considered as examples of tumour-inducing agents, and human papilloma viruses (HPVs) are associated with benign self-limiting cutaneous and mucosal proliferation in their natural hosts. Cervical cancer is the leading gynaecological malignancy worldwide, and its incidence is very high in Indian women.1e3 Current biological and epidemiological data strongly relate certain HPV types to cervical oncogenesis,4,5 but their oncogenic potential and prevalence differ geographically and by ethnicity. Molecular epidemiological studies on cervical cancer from India show HPV positivity rates as high as 98% in women with invasive cancer, with HPV type 16 accounting for more than 90%.6 A meta-analysis of nine studies from India by Bhatla et al. revealed an overall HPV prevalence of 12% in women with normal cytology and 94.6% in women with invasive cervical cancer.7 Despite the high incidence of cervical cancer in India, few large-scale population-based studies have been conducted on the prevalence and genotype distribution of HPV. The HPV type distribution among the HPV-positive cancers in
a rural community in Hyderabad showed that HPV types 16 (66.7%) and 18 (19.4%) were most common, followed by HPV types 33, 35, 45, 52 , 58, 59 and 73.8 The Andaman and Nicobar Islands (92e94 East and 6e14 North), a Union Territory of India, is an archipelago of 555 islands and islets, stretching over 700 km from north to south, in the Bay of Bengal. The population of these islands is 356,000, which includes six aboriginal tribes and settlers from mainland India.9 Health care in these islands is almost entirely provided by the Government. G.B. Pant Hospital in Port Blair is the only referral hospital on the Andaman and Nicobar Islands. Nothing is known about the prevalence of HPV infection in the tribal and non-tribal populations of these islands. Following the recent development of two HPV vaccines that offer an opportunity for control of HPV infection, and therefore cervical cancer,10 there is an urgent need for HPV prevalence data from all regions of India, including the Andaman and Nicobar Islands. The present study was designed as preliminary research to investigate the prevalence of high-risk HPV types 16 and 18 among the tribal and non-tribal populations of the Andaman and Nicobar Islands. This study included married women aged 20e60 years presenting with symptoms of persistent vaginal discharge, intermenstrual bleeding, postcoital bleeding and postmenopausal bleeding at G.B. Pant Hospital, Port Blair and BJR Hospital, Car Nicobar. One hundred and ten women (67 nontribal and 43 tribal) attending the gynaecology outpatient departments of these two hospitals were included in the study. Their informed consent was obtained after provision
* Corresponding author. Tel.: þ91 3192 251158/251164; fax: þ91 3192 251163. E-mail address: [email protected] (P. Vijayachari). 0033-3506/$ e see front matter ª 2011 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.puhe.2011.09.018
68
p u b l i c h e a l t h 1 2 6 ( 2 0 1 2 ) 6 7 e6 9
Table 1 e Prevalence of gynaecological symptoms among the study subjects. Symptoms
n
%
Persistent vaginal discharge Intermenstrual bleeding Dysuria Lowbackache Postmenopausal bleeding Menstrual abnormalities Postcoital bleeding
63 19 10 7 6 3 2
57.3 17.3 9.1 6.4 5.4 2.7 1.8
Ethical approval Ethical clearance was obtained from the Institutional Ethical Committee.
Funding This study was supported by the intramural funds of the Indian Council of Medical Research.
Competing interests None declared.
of information about the study, the gynaecological procedure for specimen collection and the screening test. The women were interviewed to obtain demographic and socio-economic data and their medical history. A clinical examination was performed, and cervical scrapes were collected from the ectocervix by the standard procedure using an Ayer’s spatula. DNA was extracted from the cervical samples, and all samples were screened by polymerase chain reaction (PCR) in accordance with the published protocol6 using L1 consensus primers for HPV detection. Further typing was performed for HPV types 16 and 18 using type-specific primers. Table 1 shows the frequency of gynaecological symptoms among the study population. Of the 110 women screened, four [3.6%, 95% confidence interval (CI) 1.2e9.6] tested positive for HPV infection. Further HPV typing using type-specific primers showed that all four women were positive for HPV type 16. One of the four HPV-positive women was co-infected with high-risk HPV types 16 and 18. Of the 43 women from the indigenous Nicobarese tribe, one (2.3%) was positive for HPV type 16. Among the four women infected with highrisk HPV types, two had invasive squamous carcinoma, one had an inflammatory Pap smear, and one had a normal Pap smear. This is the first report of high-risk HPV infection among the women of the Andaman and Nicobar Islands. This study found a prevalence of high-risk HPV of 3.6%, which is lower than that reported for the population of India (5e15%),11e13 although the sample size was small. A similar prevalence of high-risk HPV (3.9%) was reported in two communities near Trivandrum in Southern India.14 An important finding of the present study was the detection of HPV type 16 infection among the indigenous Nicobarese tribe, although the prevalence was low (2.3%, 95% CI 0.01e13.8). There is a need to screen a larger sample of Nicobarese women in order to obtain a more precise estimate. It is important to estimate the prevalence of high-risk HPV infection in order to assess the cost-effectiveness of a vaccination programme for the control of cervical cancer, because vaccines with proven efficacy and safety are not available. This issue is of high public health importance for small and isolated populations such as the Nicobarese. If the incidence rates for HPV infection and, as a consequence, cervical cancer are high, vaccination could be an effective tool to reduce morbidity and mortality as near-total coverage could be achieved in such populations. This study is a preliminary step towards this goal. A larger study is being planned.
Acknowledgements We are grateful to the Dr. Eapen Titus, Medical Superintendent, BJR Hospital, Car Nicobar, for his kind cooperation for carrying out the study at Car Nicobar islands.
references
1. Murthy NS, Juneja A, Sehgal A, Prabhakar AK, Luthra UK. Cancer projection by the turn of century-Indian Scene. Ind J Cancer 1990;27:74e82. 2. National Cancer Registry Project. Biennial report 2001. New Delhi: Indian Council of Medical Research; 2001. 3. Perkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics 2002. CA Cancer J Clin 2005;55:74e108. 4. Villa LL. Human papillomavirus and cervical cancer. Adv Cancer Res 1997;71:321e41. 5. Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV, et al. Epidemiological classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003;348:518e27. 6. Das BC, Sharma JK, Gopalkrishna V, Das DK, Singh V, Gissmann L, et al. A high frequency of human papillomavirus DNA sequences in cervical carcinoma of Indian women as revealed by southern blot hybridisation and polymerase chain reaction. J Med Virol 1992;36:239e45. 7. Bhatla N, Lal N, Bao YP, Ng T, Qiao YL. A meta-analysis of human papillomavirus type-distribution in women from South Asia: implications for vaccination. Vaccine 2008;26: 2811e7. 8. Sowjanya PA, Jain M, Poli UR, Padma S, Das M, Shah KV, et al. Prevalence and distribution of high-risk human papilloma virus (HPV) types in invasive squamous cell carcinoma of the cervix and in normal women in Andhra Pradesh, India. BMC Infect Dis:116. Available at: http://www. biomedcentral.com/1471-2334/5/116, 2005;5. (last date of accessed 10 July, 2011). 9. Andaman and Nicobar administration. Know Andaman. Directorate of Economics and Statistics, Andaman and Nicobar administration, Port Blair. 2007. Available from http://www.and.nic.in. (last date of accessed December 2010). 10. Basu P, Chowdhury D. Cervical cancer screening & HPV vaccination: a comprehensive approach to cervical cancer control. Ind J Med Res 2009;130:241e6. 11. Gjooen K, Oslen AO, Magnus P, Grinde B, Sauer T, Orstavik I. Prevalence of human papillomavirus in cervical scrapes as analyzed by PCR, in a population based sample of women
p u b l i c h e a l t h 1 2 6 ( 2 0 1 2 ) 6 7 e6 9
with and without cervical dysplasia. Acta Pathologica, Microbiologica et Immunologica Scandinavica 1996;104:68e74. 12. Siritantikorn S, Laiwejpithaya S, Siripanyaphinyo U, Auewarakul P, Yenchitsomanus P, Thakernpol K, et al. Detection and typing of human papillomavirus DNAs in normal cervix, intraepithelial neoplasia and cervical cancer in Bangkok. Southeast Asian J Trop Med Publ Health 1997;28: 707e10.
69
13. Munoz N, Herraro R, Lazcano E, Posso H, Matos E, Sukvirach S, et al. HPV prevalence survey in the general populations. In: Abstract book of the 4th international multidisciplinary congress. Paris: Eurogin; 2000. 14. Gilham C, Varghese C, Gibson I, Peto J. HPV infection in a population-based cohort study in Kerala, India. 23rd International Papillomavirus Conference & Clinical Workshop, 1e7 September 2006, Prague.
Available online at www.sciencedirect.com
Public Health journal homepage: www.elsevier.com/puhe
Short Communication
High-risk HPV infection among the tribal and non-tribal women of the Andaman and Nicobar Islands, India R. Parvez a, S. Hedau b, D. Bhattacharya a, H. Bhattacharjee a, N. Muruganandam a, B.C. Das b, M.K. Saha c, A.P. Sugunan a, P. Vijayachari a,* a
Regional Medical Research Centre (ICMR), WHO Collaborating Centre for Diagnosis, Research, Reference and Training in Leptospirosis, Post Bag No. 13, Dollygunj, Port Blair 744101, Andaman and Nicobar Islands, India b Institute of Cytology and Preventive Oncology, I-7, Sectore39, Noida 201301, India c G.B. Pant Hospital, Port Blair 744101, Andaman and Nicobar Islands, India
article info Article history: Received 8 April 2010 Received in revised form 18 July 2011 Accepted 21 September 2011 Available online 29 November 2011
Papovaviruses have long been considered as examples of tumour-inducing agents, and human papilloma viruses (HPVs) are associated with benign self-limiting cutaneous and mucosal proliferation in their natural hosts. Cervical cancer is the leading gynaecological malignancy worldwide, and its incidence is very high in Indian women.1e3 Current biological and epidemiological data strongly relate certain HPV types to cervical oncogenesis,4,5 but their oncogenic potential and prevalence differ geographically and by ethnicity. Molecular epidemiological studies on cervical cancer from India show HPV positivity rates as high as 98% in women with invasive cancer, with HPV type 16 accounting for more than 90%.6 A meta-analysis of nine studies from India by Bhatla et al. revealed an overall HPV prevalence of 12% in women with normal cytology and 94.6% in women with invasive cervical cancer.7 Despite the high incidence of cervical cancer in India, few large-scale population-based studies have been conducted on the prevalence and genotype distribution of HPV. The HPV type distribution among the HPV-positive cancers in
a rural community in Hyderabad showed that HPV types 16 (66.7%) and 18 (19.4%) were most common, followed by HPV types 33, 35, 45, 52 , 58, 59 and 73.8 The Andaman and Nicobar Islands (92e94 East and 6e14 North), a Union Territory of India, is an archipelago of 555 islands and islets, stretching over 700 km from north to south, in the Bay of Bengal. The population of these islands is 356,000, which includes six aboriginal tribes and settlers from mainland India.9 Health care in these islands is almost entirely provided by the Government. G.B. Pant Hospital in Port Blair is the only referral hospital on the Andaman and Nicobar Islands. Nothing is known about the prevalence of HPV infection in the tribal and non-tribal populations of these islands. Following the recent development of two HPV vaccines that offer an opportunity for control of HPV infection, and therefore cervical cancer,10 there is an urgent need for HPV prevalence data from all regions of India, including the Andaman and Nicobar Islands. The present study was designed as preliminary research to investigate the prevalence of high-risk HPV types 16 and 18 among the tribal and non-tribal populations of the Andaman and Nicobar Islands. This study included married women aged 20e60 years presenting with symptoms of persistent vaginal discharge, intermenstrual bleeding, postcoital bleeding and postmenopausal bleeding at G.B. Pant Hospital, Port Blair and BJR Hospital, Car Nicobar. One hundred and ten women (67 nontribal and 43 tribal) attending the gynaecology outpatient departments of these two hospitals were included in the study. Their informed consent was obtained after provision
* Corresponding author. Tel.: þ91 3192 251158/251164; fax: þ91 3192 251163. E-mail address: [email protected] (P. Vijayachari). 0033-3506/$ e see front matter ª 2011 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.puhe.2011.09.018
68
p u b l i c h e a l t h 1 2 6 ( 2 0 1 2 ) 6 7 e6 9
Table 1 e Prevalence of gynaecological symptoms among the study subjects. Symptoms
n
%
Persistent vaginal discharge Intermenstrual bleeding Dysuria Lowbackache Postmenopausal bleeding Menstrual abnormalities Postcoital bleeding
63 19 10 7 6 3 2
57.3 17.3 9.1 6.4 5.4 2.7 1.8
Ethical approval Ethical clearance was obtained from the Institutional Ethical Committee.
Funding This study was supported by the intramural funds of the Indian Council of Medical Research.
Competing interests None declared.
of information about the study, the gynaecological procedure for specimen collection and the screening test. The women were interviewed to obtain demographic and socio-economic data and their medical history. A clinical examination was performed, and cervical scrapes were collected from the ectocervix by the standard procedure using an Ayer’s spatula. DNA was extracted from the cervical samples, and all samples were screened by polymerase chain reaction (PCR) in accordance with the published protocol6 using L1 consensus primers for HPV detection. Further typing was performed for HPV types 16 and 18 using type-specific primers. Table 1 shows the frequency of gynaecological symptoms among the study population. Of the 110 women screened, four [3.6%, 95% confidence interval (CI) 1.2e9.6] tested positive for HPV infection. Further HPV typing using type-specific primers showed that all four women were positive for HPV type 16. One of the four HPV-positive women was co-infected with high-risk HPV types 16 and 18. Of the 43 women from the indigenous Nicobarese tribe, one (2.3%) was positive for HPV type 16. Among the four women infected with highrisk HPV types, two had invasive squamous carcinoma, one had an inflammatory Pap smear, and one had a normal Pap smear. This is the first report of high-risk HPV infection among the women of the Andaman and Nicobar Islands. This study found a prevalence of high-risk HPV of 3.6%, which is lower than that reported for the population of India (5e15%),11e13 although the sample size was small. A similar prevalence of high-risk HPV (3.9%) was reported in two communities near Trivandrum in Southern India.14 An important finding of the present study was the detection of HPV type 16 infection among the indigenous Nicobarese tribe, although the prevalence was low (2.3%, 95% CI 0.01e13.8). There is a need to screen a larger sample of Nicobarese women in order to obtain a more precise estimate. It is important to estimate the prevalence of high-risk HPV infection in order to assess the cost-effectiveness of a vaccination programme for the control of cervical cancer, because vaccines with proven efficacy and safety are not available. This issue is of high public health importance for small and isolated populations such as the Nicobarese. If the incidence rates for HPV infection and, as a consequence, cervical cancer are high, vaccination could be an effective tool to reduce morbidity and mortality as near-total coverage could be achieved in such populations. This study is a preliminary step towards this goal. A larger study is being planned.
Acknowledgements We are grateful to the Dr. Eapen Titus, Medical Superintendent, BJR Hospital, Car Nicobar, for his kind cooperation for carrying out the study at Car Nicobar islands.
references
1. Murthy NS, Juneja A, Sehgal A, Prabhakar AK, Luthra UK. Cancer projection by the turn of century-Indian Scene. Ind J Cancer 1990;27:74e82. 2. National Cancer Registry Project. Biennial report 2001. New Delhi: Indian Council of Medical Research; 2001. 3. Perkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics 2002. CA Cancer J Clin 2005;55:74e108. 4. Villa LL. Human papillomavirus and cervical cancer. Adv Cancer Res 1997;71:321e41. 5. Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV, et al. Epidemiological classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003;348:518e27. 6. Das BC, Sharma JK, Gopalkrishna V, Das DK, Singh V, Gissmann L, et al. A high frequency of human papillomavirus DNA sequences in cervical carcinoma of Indian women as revealed by southern blot hybridisation and polymerase chain reaction. J Med Virol 1992;36:239e45. 7. Bhatla N, Lal N, Bao YP, Ng T, Qiao YL. A meta-analysis of human papillomavirus type-distribution in women from South Asia: implications for vaccination. Vaccine 2008;26: 2811e7. 8. Sowjanya PA, Jain M, Poli UR, Padma S, Das M, Shah KV, et al. Prevalence and distribution of high-risk human papilloma virus (HPV) types in invasive squamous cell carcinoma of the cervix and in normal women in Andhra Pradesh, India. BMC Infect Dis:116. Available at: http://www. biomedcentral.com/1471-2334/5/116, 2005;5. (last date of accessed 10 July, 2011). 9. Andaman and Nicobar administration. Know Andaman. Directorate of Economics and Statistics, Andaman and Nicobar administration, Port Blair. 2007. Available from http://www.and.nic.in. (last date of accessed December 2010). 10. Basu P, Chowdhury D. Cervical cancer screening & HPV vaccination: a comprehensive approach to cervical cancer control. Ind J Med Res 2009;130:241e6. 11. Gjooen K, Oslen AO, Magnus P, Grinde B, Sauer T, Orstavik I. Prevalence of human papillomavirus in cervical scrapes as analyzed by PCR, in a population based sample of women
p u b l i c h e a l t h 1 2 6 ( 2 0 1 2 ) 6 7 e6 9
with and without cervical dysplasia. Acta Pathologica, Microbiologica et Immunologica Scandinavica 1996;104:68e74. 12. Siritantikorn S, Laiwejpithaya S, Siripanyaphinyo U, Auewarakul P, Yenchitsomanus P, Thakernpol K, et al. Detection and typing of human papillomavirus DNAs in normal cervix, intraepithelial neoplasia and cervical cancer in Bangkok. Southeast Asian J Trop Med Publ Health 1997;28: 707e10.
69
13. Munoz N, Herraro R, Lazcano E, Posso H, Matos E, Sukvirach S, et al. HPV prevalence survey in the general populations. In: Abstract book of the 4th international multidisciplinary congress. Paris: Eurogin; 2000. 14. Gilham C, Varghese C, Gibson I, Peto J. HPV infection in a population-based cohort study in Kerala, India. 23rd International Papillomavirus Conference & Clinical Workshop, 1e7 September 2006, Prague.