Clinical evaluation of HPV DNA test combined with liquid-based cytology in the diagnosis of cervical disease

Raghvendra Thakur, Jasma Mally, Rajina Shrestha, Xuehua Zheng, Mengli Zhang, Yanjun Wu, Neelima Bajracharya, Guiying Zheng

Department of Obstetrics and Gynecology, First Hospital of Jilin University, Norman Bethune College of Medicine, Changchun, China.
Department of Obstetrics and Gynecology, Jiamusi University, Jiamusi, China.
Department of Obstetrics and Gynecology, Maternity and Children Hospital of Jilin Province, Liaoyuan, China.
Department of Obstetrics and Gynecology, Second Hospital of Jilin University, Norman Bethune College of Medicine, Changchun, China.

DOI: 10.4236/ojog.2013.33068                

Abstract

Objectives: To evaluate the sensitivity and accuracy of the HPV DNA test in conjunction with thin prep cytology test as a screening method of human papillomavirus (HPV) infection. To study either the cervical erosion is related to high risk HPV infection or to determine the mean age distribution that is more prone to HPV infection. Material and Methods: The study is a retrospective cohort implemented to determine the real performance of liquid based medium and HPV DNA testing combined in second clinical hospital of Jilin University Changchun, China. The study group included total 150 patients from January 1, 2011 to December 30, 2012. A computerized search identified patients with thin prep test results and high risk HPV DNA testing during a 2-year period was recruited. The patients were chosen after proper speculum examination followed by thin prep cytology (TCT) and HPV DNA test. Cytologic specimens were obtained with endocervical brush, which was rinsed into the vial of Cytyc. The residual samples after the cytology report were taken for reflex HPV DNA test. The manufacture protocol was followed for HPV DNA testing using Hybrid Capture II. Colposcopic biopsy was performed for the diagnosis purpose, in patients who had atypical squamous cells of undeter-mined significance (AUS-US), low grade intraepithelial lesion (LSIL) or high-grade intraepithelial lesion (HSIL) in cytology and with positive results of highrisk HPV DNA. The diagnostic criteria were based on the Bethesda System (TBS). Findings: The high risk HPV positive women with abnormal cytology had a CIN I risk of 73 (86%), whereas 35 (23.3%) high-risk HPV positive women out of 109 (72.7%) normal cytology who underwent histological biopsy had CIN I 16 (10.7%). The risk for cervical intraepithelial neoplasia (CIN) in women with high-risk HPV positive with normal cytology was higher among women invited for the first time 31 - 40 years of age 12 (8%) than among older women 1 (0.7%). Out of 44 (29.3%) women who had I degree erosion with 6 (14%) positive HPV DNA test 38 (86%) had a normal histology biopsy showing no statically significant between them. Conclusion: The data confirm that HR-HPV DNA testing is much more sensitive than cytology alone and that HPV DNA testing helps in identifying women with high risk of serious cervical disease in an efficient and medically acceptable manner. The other most significant advantage of this cervical cancer screening method is that women who are HPV DNA positive can easily and quickly referred for colposcopic examination (within one year), which could identify the precancerous and cancer stage. And those who are HPV DNA negative can safely have much longer screening intervals saving considerable costs. With mean age being 38 ± 10 years, age older than 30 years should undergo HPV DNA testing with cytology triage in primary screening. But in woman younger than 30 years using HPV DNA assay, as an initial screening step can increase the prevalence of abnormal smears and the positive predictive value of HPV followed by TCT. However, close follow-up is essential if the initial biopsy is negative because a considerable number of women may have HPV infection positive in subsequent studies.

Keywords

Human Papillomavirus; Thin-Prep Cytology Test; Hybrid Capture; Cervical Intraepithelial Neoplasia; Bethesda System; Colposcopy Examination

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Schiffman, M. and Castle, P.E. (2003) Human papillomavirus: Epidemiology and public health. Archives of Pathology & Laboratory Medicine, 127, 930-934.
[2]	Gillison, M.L. (2004) Human papillomavirus-associated head and neck cancer is a distinct epidemiologic, clinical, and molecular entity. Seminars in Oncology, 31, 744-754. doi:10.1053/j.se minoncol.2004.09.011
[3]	Goldstein, M.A., Goodman, A., Del Carmen, M.G. and Wilbur, D.C. (2009) Case records of the Massachusetts General Hospital. Case 10-2009. New England Journal of Medicine, 360, 1337-1344.
[4]	Kahn, J.A. (2009) HPV vaccination for the prevention of cervical intraepithelial neoplasia. New England Journal of Medicine, 361, 271-278. doi:10.1056/NEJMct0806938
[5]	NCCC National Cervical Cancer Coalition, 218-226. Retrieved 1 July 2008. www.nccn.org/pro fessionals/physician_gls/ f_guidel ines.asp#cervical
[6]	Peto, J., Gilham, C., Fletcher, O. and Matthews, F.E. (2004) The cervical cancer epidemic that screening has prevented in the UK. Lancet, 364, 249-256. doi:10.1016/S0140-6736(04)16674-9
[7]	Solomon, D., Schiffman, M., Tarone, R. and The ALTS Study Group (2001) Comparison of three management strategies for patients with atypical squamous cells of undetermined significance: Baseline results from a randomized trial. Journal of the National Cancer Institute, 93, 293-299. doi:10.1093/jnci/93.4.293
[8]	Ronco, G., Cuzick, J., Pierotti, P., et al. (2007) Accuracy of liquid based versus conventional cytology: Overall results of new technologies for cervical cancer screening randomized controlled trial. British Medical Journal, 335, 28. doi:10.1136/bmj.39196.740995.BE
[9]	Coste, J., Cochand-Priollet, B., De Cremoux, P., et al. (2003) Cross sectional study of conventional cervical smear, monolayer cytology, and human papillomavirus DNA testing for cervical cancer screening. British Medical Journal, 326, 733. doi:10.1136/bmj.326.7392.733
[10]	Tristram, A. and Fiander, A. (2007) Human papillomavirus (including vaccines). Obstetrics, Gynaecology and Reproductive Medicine, 17, 324-329. doi:10.1016/j.ogrm.2007.08.006
[11]	Davies, P., Kornegay, J. and Iftner, T. (2001) Current methods of testing for human papillomavirus. Best Practice and Research in Clinical Obstetrics and Gynaecology, 15, 677-700. doi:10.1053/beog.2001.0214
[12]	De Cremoux, P., Coste, J., Sastre-Garau, X., et al. (2003) Efficiency of the Hybrid Capture 2 HPV DNA test in cervical cancer screening: A study by the French Society of Clinical Cytology. American Journal of Clinical Pathology, 120, 492-499. doi:10.1309/XFUCPP6M5XUA94B8
[13]	Klinkhamer, P.J., Vooijs, G.P. and De Haan, A.F. (1988) Intraobserver and interobserver variability in the diagnosis of epithelial abnormalities in cervical smears. Acta Cytologica, 32, 794-800.
[14]	Parker, M.F., Zahn, C.M., Vogel, K.M., et al. (2002) Discrepancy in the interpretation of cervical histology by gynecologic pathologists. Obstetrics & Gynecology, 100, 277-280. doi:10.1016/S0029-7844(02)02058-6
[15]	Ho, G.Y., Bierman, R., Beardsley, L., et al. (1998) Natural history of cervicovaginal papillomavirus infection in young women. The New England Journal of Medicine, 338, 423-428. doi:10.1056/NEJM199802123380703
[16]	Woodman, C.B., Collins, S., Winter, H., et al. (2001) Natural history of cervical human papillomavirus infection in young women: A longitudinal cohort study. Lancet, 357, 1831-1836. doi:10.1016/S0140-6736(00)04956-4
[17]	Richart, R.M. and Barron, B.A. (1969) A follow-up study of patients with cervical dysplasia. American Journal of Obstetrics and Gynecology, 105, 386-393.
[18]	Nasiell, K., Nasiell, M. and Vaclavinkova, A. (1983) Behavior of moderate cervical dysplasia during long-term follow-up. Obstetrics and Gynecology, 61, 609-614.