DOI QR코드

DOI QR Code

Use of Fast Transfer Analysis Cartridges for Cervical Sampling and Real Time PCR Based High Risk HPV Testing in Cervical Cancer Prevention - a Feasibility Study from South India

  • Published : 2015.09.02

Abstract

Background: Molecular testing for human papillomavirus (HPV) is the most objective and reproducible of all cervical cancer screening tests and also less demanding in terms of training and quality assurance. However, there is an impending need for cost effective molecular HPV testing methods with sampling ease, easy storage measures and minimum turn around times suitable for a low resource setting. Objective : Our aim was to evaluate the feasibility of using a fast transfer analysis (FTA) mini elute cartridge for cervical sampling to identify high risk HPV by real time PCR and to compare molecular HPV testing and Pap cytology testing to predict histologically confirmed cervical precancer (CIN 2+ lesions) in a cervical cancer prevention program. Materials and Methods: This was conducted as a pilot study (n=200) on women sampled using FTA mini elute cartridges, genotyped by two different real time PCR assays, detecting 13 high risk HPV (HR HPV) species, including HPV16 along with its physical DNA status. Results obtained from each of the tests were compared and analysed using suitable statistical tests. Results: With FTA mini elute cartridge samples HR HPV positivity was seen in 48/200 (24%). Of these, presence of HPV 16 DNA was observed in 28/48 (58.3%) women. High risk HPV was positive in 20% (37/185) of women with benign cytology and 73.3% (11/15) of women with abnormal cytology findings. A very significant correlation (${\chi}^2=22.090$ ; p=0.000) was observed between cytology and HR HPV findings showing an increasing trend of HR HPV prevalence in 50% (1/2) of LSIL, 75% (3/4) of HSIL and 100% (3/3) of SCC. Of the CIN 2+ lesions identified by histopathology, 88.9% (8/9) had HR HPV. A significant association (${\chi}^2=11.223$ ; p=0.001) of HR HPV and histopathologically confirmed CIN 2+ lesions was found. Sensitivity of the two tests were comparable but specificity of Pap testing was better (90.7% vs 70.4%) to predict histopathologically diagnosed cervical precancers. Conclusions: The current study explored the feasibility of using a FTA mini elute cartridge for cervical sampling for the first time in India as a part of a community based cervical cancer prevention program. We suggest that FTA based sampling is suitable and feasible for real time based HPV testing. Molecular HR HPV testing can be more sensitive and useful to identify high risk women requiring Pap testing which is more specific to detect histologically confirmed cervical precancer.

Keywords

References

  1. Almonte M, Ferreccio C, Luciani S, et al. (2015) Visual inspection after acetic acid (VIA) is highly heterogeneous in primary cervical screening in Amazonian Peru. PLoS one, 10, 115355-67
  2. Argyri E, Papaspyridakos S, Tsimplaki E, et al (2013). A cross sectional study of HPV type prevalence according to age and cytology. BMC Infect Dis, 13, 53-8. https://doi.org/10.1186/1471-2334-13-53
  3. Bhatla N, Dar L, Patro AR, et al (2009). Can human HPV in Healthy Women of North East India papillomavirus DNA testing of self-collected vaginal samples compare with physician-collected cervical samples and cytology for cervical cancer screening in developing countries? Cancer Epidemiol, 33, 446-50. https://doi.org/10.1016/j.canep.2009.10.013
  4. Cox JT, Castle PE, Behrens CM, et al (2013). Comparison of cervical cancer screening strategies incorporating different combinations of cytology, HPV testing, and genotyping for HPV 16/18: results from the ATHENA HPV study. Am J Obstet Gynecol, 208, 184.
  5. de Bie RP, Schmeink CE, Bakkers JM, et al (2011) The indicating FTA elute cartridge a solid sample carrier to detect highrisk HPV and high-grade cervical lesions. J Mol Diagn, 13, 371-6. https://doi.org/10.1016/j.jmoldx.2011.02.003
  6. Ferlay J, Soerjomataram I, Ervik M, et al (2013). GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No.11[Internet]. Lyon, France: International Agency for Research on Cancer.
  7. Goldie SJ, Gaffikin L, Goldhaber-Fiebert JD, et al (2005). Cost effectiveness of cervical cancer screening in five developing countries. N Engl J Med, 353, 2158-68. https://doi.org/10.1056/NEJMsa044278
  8. Gustavsson I, Lindell M, Wilander E, et al (2009) Use of FTA card for dry collection, transportation and storage of cervical cell specimen to detect high-risk HPV. J Clin Virol, 46, 112-116 https://doi.org/10.1016/j.jcv.2009.06.021
  9. Gyllensten U, Gustavsson I, Lindell M, et al (2012). Primary high-risk HPV screening for cervical cancer in postmenopausal women. Gynecol Oncol, 125, 343-5 https://doi.org/10.1016/j.ygyno.2012.01.036
  10. Huh WK, Ault KA, Chelmow D, et al (2015). Use of primary high-risk human papillomavirus testing for cervical cancer screening: Interim clinical guidance. Gynecol Oncol, 136, 178-82. https://doi.org/10.1016/j.ygyno.2014.12.022
  11. Jemal A, Bray F, Center MM, et al. Global cancer statistics (2011). CA Cancer J Clin, 61, 69-90 https://doi.org/10.3322/caac.20107
  12. Kailash U, Hedau S, Gopalkrishna V, et al. (2002). A simple 'paper smear' method for dry collection, transport and storage of cervical cytological specimens for rapid screening of HPV infection by PCR. J Med Microbiol, 51, 606-10. https://doi.org/10.1099/0022-1317-51-7-606
  13. Katyal S, Mehrotra R (2011). Complementary procedures in cervical cancer screening in low resource settings. J Obstet Gynaecol India, 61, 436-8 https://doi.org/10.1007/s13224-011-0067-y
  14. Khan MJ, Castle PE, Lorincz AT, et al. (2005). The elevated 10-year risk of cervical precancer and cancer in women with human papillomavirus (HPV) type 16 or 18 and the possible utility of type-specific HPV testing in clinical practice. J Natl Cancer Inst, 97, 1072-9. https://doi.org/10.1093/jnci/dji187
  15. Kim K1, Kim JJ, Kim SM, et al (2012). Prevalence and determinants of high-risk human papillomavirus infection in women with high socioeconomic status in Seoul, Republic of Korea. Asian Pac J Cancer Prev, 13, 269-73. https://doi.org/10.7314/APJCP.2012.13.1.269
  16. Kitchener HC, Almonte M, Thomson C et al (2009). HPV testing in combination with liquid-based cytology in primary cervical screening (ARTISTIC): a randomised controlled trial. Lancet Oncol, 10, 672-82. https://doi.org/10.1016/S1470-2045(09)70156-1
  17. Leinonen MK, Nieminen P, Lonnberg S, et al (2012). Detection rates of precancerous and cancerous cervical lesions within one screening round of primary human papillomavirus DNA testing: prospective randomised trial in Finland. BMJ, 345, 77896-906.
  18. Malila N, Leinonen M, Kotaniemi-Talonen L, et al (2013). The HPV test has similar sensitivity but more over diagnosis than the Pap test--a randomised health services study on cervical cancer screening in Finland. Int J Cancer, 132, 2141-7 https://doi.org/10.1002/ijc.27850
  19. Monsonego J1, (2004). Colposcopy: the value of HPV testing in clinical practice. Gynecol Obstet Fertil, 32, 62-74. https://doi.org/10.1016/j.gyobfe.2003.10.025
  20. Monsonego J, Cox JT, Behrens C, et al (2015). Prevalence of high-risk human papilloma virus genotypes and associated risk of cervical precancerous lesions in a large U.S. screening population: Data from the ATHENA trial. Gynecol Oncol, 137, 47-54.
  21. Ogilvie GS, Krajden M, van Niekerk DJ, et al (2012). Primary cervical cancer screening with HPV testing compared with liquid-based cytology: results of round 1 of a randomised controlled trial -- the HPV FOCAL Study. Br J Cancer, 107, 1917-24. https://doi.org/10.1038/bjc.2012.489
  22. Parashari A, Singh V. (2013) Reasons for variation in sensitivity and specificity of visual inspection with acetic acid (VIA) for the detection of pre- cancer and cancer lesions of uterine cervix. Asian Pac J Cancer Prev, 14, 7761-2. https://doi.org/10.7314/APJCP.2013.14.12.7761
  23. Parham GP, Mwanahamuntu MH, Pfaendler KS, et al (2010). eC3--a modern telecommunications matrix for cervical cancer prevention in Zambia. J Low Genit Tract Dis, 14, 167-73. https://doi.org/10.1097/LGT.0b013e3181cd6d5e
  24. Pimple S, Shastri SS. (2014). Comparative evaluation of human papilloma virus-DNA test verses colposcopy as secondary cervical cancer screening test to triage screen positive women on primary screening by visual inspection with 5% acetic acid. Indian J Cancer, 5, 117-23.
  25. Phongsavan K, Gustavsson I, Marions L, et al (2012). Detection of human papillomavirus among women in Laos: feasibility of using filter paper card and prevalence of high-risk types. Int J Gynecol Cancer, 22, 1398-406. https://doi.org/10.1097/IGC.0b013e3182664b6b
  26. Rai AK, Das D, Kataki AC, et al. (2014). Hybrid capture 2 assay based evaluation of high-risk HPV status in healthy women of north-east India. Asian Pac J Cancer Prev, 15, 861-5. https://doi.org/10.7314/APJCP.2014.15.2.861
  27. Ramshankar V, Soundara VT, Shyamsundar V, et al. (2014). Risk stratification of early stage oral tongue cancers based on HPV status and p16 immunoexpression. Asian Pac J Cancer Prev, 15, 8351-9. https://doi.org/10.7314/APJCP.2014.15.19.8351
  28. Rijkaart DC, Heideman DA, Coupe VM, et al (2012). High-risk human papillomavirus (hrHPV) E6/E7 mRNA testing by PreTect HPV-Proofer for detection of cervical high-grade intraepithelial neoplasia and cancer among hrHPV DNApositive women with normal cytology. J Clin Microbiol. 50, 2390-6. https://doi.org/10.1128/JCM.06587-11
  29. Ronco G, Dillner J, Elfstrom KM, et al (2014). International HPV screening working group. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet, 383, 524-32 https://doi.org/10.1016/S0140-6736(13)62218-7
  30. Sankaranarayanan R, Esmy PO, Rajkumar R, et al (2007) Effect of visual screening on cervical cancer incidence and mortality in Tamil Nadu, India: a cluster-randomised trial. Lancet, 370, 398-406. https://doi.org/10.1016/S0140-6736(07)61195-7
  31. Sarma U, Mahanta J, Borkakoty B, et al (2015). Distribution of human papilloma virus infections of uterine cervix among women of reproductive age--a cross sectional hospital-based study from North East India. Asian Pac J Cancer Prev, 16, 1519-23. https://doi.org/10.7314/APJCP.2015.16.4.1519
  32. Sherigar B, Dalal A, Durdi G, et al (2010). Cervical cancer screening by visual Inspection with acetic acid - interobserver variability between nurse and physician. Asian Pac J Cancer Prev, 11, 619-22.
  33. Solomon D, Davey D, Kurman R, et al. (2002). The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA, 287, 2114-9. https://doi.org/10.1001/jama.287.16.2114
  34. Sowjanya AP, Jain M, Poli UR, et al (2005). 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, 5, 116-23. https://doi.org/10.1186/1471-2334-5-116
  35. Sowjanya AP, Paul P, Vedantham H, et al (2009). Suitability of self-collected vaginal samples for cervical cancer screening in periurban villages in Andhra Pradesh, India. Cancer Epidemiol Biomarkers Prev, 18, 1373-8 https://doi.org/10.1158/1055-9965.EPI-08-1171
  36. Tao K, Yan J, Yang H, et al (2014). Comparative study of the Cervista and Hybrid Capture 2 methods in detecting high-risk human papillomavirus in cervical lesions. Diagn Cytopathology, 42, 213-7. https://doi.org/10.1002/dc.23025
  37. Thulaseedharan JV1, Malila N, Hakama M, et al (2013). Effect of screening on the risk estimates of socio demographic factors on cervical cancer- a large cohort study from rural India. Asian Pac J Cancer Prev, 14, 589-94. https://doi.org/10.7314/APJCP.2013.14.1.589
  38. Wright TC Jr, Stoler MH, Sharma A, et al (2011). Evaluation of HPV-16 and HPV-18 genotyping for the triage of women with high-risk HPV+ cytology-negative results. Am J Clin Pathol, 136, 578-86 https://doi.org/10.1309/AJCPTUS5EXAS6DKZ