HPV Genotyping Linear Assay Test Comparison in Cervical Cancer Patients: Implications for HPV Prevalence and Molecular Epidemiology in a Limited-resource Area in Bandung, Indonesia

  • Panigoro, Ramdan (Department of Biochemistry, Hasan Sadikin Hospital) ;
  • Susanto, Herman (Department of Obstetrics and Gynecology, Hasan Sadikin Hospital) ;
  • Novel, Sinta Sasika (Health Research Unit, Faculty of Medicine Universitas Padjadjaran) ;
  • Hartini, Sri (Lab of Clinical Pathology, Dharmais National Cancer Hospital) ;
  • Sahiratmadja, Edhyana (Department of Biochemistry, Hasan Sadikin Hospital)
  • Published : 2013.10.30


Background: Persistent infection with high risk human papillomavirus (hrHPV) is strongly associated with cervical cancer. Normal cervical cells may also harbor hrHPV, and detection of early hrHPV infection may minimize risk of cervical cancer development. This study aimed to compare two commercial HPV genotyping assays that may affordable for early screening in a limited-resource setting in Bandung, Indonesia. Materials and Methods: DNA from cervical biopsies with histologically confirmed as squamous cell cervical cacinoma were HPV genotyped by Linear Assay 1 (Roche Diagnostics, Mannheim, Germany) or Linear Assay 2 (Digene HPV Genotyping RH Test, Qiagen Gaithersburg, MD). In a subset of samples of each group, HPV genotype results were then compared. Results: Of 28 samples genotyped by linear assay 1, 22 (78.6%) demonstrated multiple infections with HPV-16 and other hrHPV types 18, 45 and/or 52. In another set of 38 samples genotyped by linear assay 2, 28 (68.4%) were mostly single infections by hrHPV type 16 or 18. Interestingly, 4 samples that had been tested by both kits showed discordant results. Conclusions: In a limited-resource area such as in Indonesia, country with a high prevalence of HPV infection a reliable cervical screening test in general population for early hrHPV detection is needed. Geographical variation in HPV genotyping result might have impacts for HPV prevalence and molecular epidemiology as the distribution in HPV genotypes should give clear information to assess the impact of HPV prophylactic vaccines.


Cervical cancer;HPV genotypes;linear assay;Bandung Indonesia


  1. de Sanjose S, Quint WG, Alemany L, et al (2010). Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol, 11, 1048-56.
  2. Aziz MF (2009). Gynecological cancer in Indonesia. J Gynecol Oncol, 20, 8-10.
  3. Bradford L, Goodman A (2013). Cervical cancer screening and prevention in low-resource settings. Clin Obstet Gynecol, 56, 76-87.
  4. Bruni L, Diaz M, Castellsague X, et al (2010). Cervical human papillomavirus prevalence in 5 continents: meta-analysis of 1 million women with normal cytological findings. J Infect Dis, 202, 1789-99.
  5. Castellsague X (2008). Natural history and epidemiology of HPV infection and cervical cancer. Gynecol Oncol, 110, 4-7.
  6. de Sanjose S, Diaz M, Castellsague X, et al. (2007). Worldwide prevalence and genotype distribution of cervical human papillomavirus DNA in women with normal cytology: a meta-analysis. Lancet Infect Dis, 7, 453-9.
  7. Domingo EJ, Noviani R, Noor MR, et al (2008). Epidemiology and prevention of cervical cancer in Indonesia, Malaysia, the Philippines, Thailand and Vietnam. Vaccine, 26, 71-9.
  8. Dona MG, Benevolo M, Pimpinelli F, et al (2011). Comparative evaluation of different DNA extraction methods for HPV genotyping by linear array and INNO-LiPA. J Med Virol, 83, 1042-7.
  9. Ge S, Gong B, Cai X, et al (2012). Prevent cervical cancer by screening with reliable human papillomavirus detection and genotyping. Cancer Med, 1, 59-67.
  10. Hoppenot C, Stampler K, Dunton C (2012). Cervical cancer screening in high- and low-resource countries: implications and new developments. Obstet Gynecol Surv, 67, 658-67.
  11. Lindemann ML, Dominguez MJ, de Antonio JC, et al (2012). Analytical comparison of the cobas HPV Test with Hybrid Capture 2 for the detection of high-risk HPV genotypes. J Mol Diagn, 14, 65-70.
  12. Martinez SB, Palomares JC, Artura A, et al (2012). Comparison of the Cobas 4800 Human Papillomavirus test against a combination of the Amplicor Human Papillomavirus and the Linear Array tests for detection of HPV types 16 and 18 in cervical samples. J Virol Methods, 180, 7-10.
  13. Rachmadi L, Jordanova ES, Kolkman-Uljee S, et al (2012). Cytomorphological analysis of uterine cervical pap smears in relation to human papillomavirus infection in Indonesian women. Acta Cytol, 56, 171-6.
  14. Munoz N, Bosch FX, de Sanjose S, et al (2003). Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med, 348, 518-27.
  15. Nandini NM, Nandish SM, Pallavi P, et al (2012). Manual liquid based cytology in primary screening for cervical cancer - a cost effective preposition for scarce resource settings. Asian Pac J Cancer Prev, 13, 3645-51.
  16. Pannone G, Rodolico V, Santoro A, et al (2012). Evaluation of a combined triple method to detect causative HPV in oral and oropharyngeal squamous cell carcinomas: p16 Immunohistochemistry, Consensus PCR HPV-DNA, and In Situ Hybridization. Infect Agent Cancer, 7, 4.
  17. Schellekens MC, Dijkman A, Aziz MF, et al (2004). Prevalence of single and multiple HPV types in cervical carcinomas in Jakarta, Indonesia. Gynecol Oncol, 93, 49-53.
  18. Smith JS, Lewkowitz AK, Qiao YL, et al (2012)Population-based human papillomavirus 16, 18, 6 and 11 DNA positivity and seropositivity in Chinese women. Int J Cancer, 131, 1388-95.
  19. Song SH, Hong JH, Kwak SH, et al (2012). Clinical performance assessment of five human papillomavirus DNA tests using liquid-based cytology samples. J Obstet Gynaecol Res, 38, 408-14.
  20. Steinau M, Onyekwuluje JM, Scarbrough MZ, et al (2012). Performance of Commercial Reverse Line Blot Assays for HPV Genotyping. J Clin Microbiol, 50, 1539-44.
  21. Vet JN, de Boer MA, van den Akker BE, et al (2008). Prevalence of human papillomavirus in Indonesia: a population-based study in three regions. Br J Cancer, 99, 214-8.
  22. Wong FKY, Ching JCY, Chow JKF (2010). Comparison of the DiagCor GenoFlow Human Papillomavirus Array Test and Roche Linear Array HPV Genotyping Test. Open Virol J, 4, 169-74.
  23. Wong OG, Lo CK, Chow JN, et al (2012). Comparison of GenoFlow HPV test and Linear Array in an Asian Screening Population. J Clin Microbiol, 50, 1691-7.

Cited by

  1. Human Papillomavirus Genotypes Profile in Cervical Cancer Patients at Dr. Hasan Sadikin General Hospital, Bandung, Indonesia vol.15, pp.14, 2014,
  2. Development of In-House Multiplex Real Time PCR for Human Papillomavirus Genotyping in Iranian Women with Cervical Cancer and Cervical Intraepithelial Neoplasia vol.15, pp.15, 2014,
  3. No Detection of 'High-risk' Human Papillomaviruses in a Group of Iranian Women with Breast Cancer vol.15, pp.9, 2014,
  4. Cloning, Expression and Bioinformatic Analysis of Human Papillomavirus Type 52 L1 Capsid Gene from Indonesian Patient vol.8, pp.3, 2014,
  5. Human Papillomavirus Genotypes among Females in Mexico: a Study from the Mexican Institute for Social Security vol.15, pp.23, 2015,