High-risk human papillomavirus type does not predict grade of cervical intraepithelial neoplasia

Purpose of investigation: The aim of this study was to examine whether HPV testing specificity for cervical intraepithelial neoplasia (CIN) grades 2 or 3 could be improved by restricting the range of HPV types classified as 'high-risk'.

Methods: DNA was extracted from 28 CIN I, nine CIN II and 13 CIN III formalin-fixed, paraffin-embedded biopsies. HPV type was determined by General Primer mediated 5+/6+ PCR assay.

Results: The prevalence of specific HPV types among the different grades of CIN and the relationship to the referral smear diagnosis was examined. HPV type-16 alone was more highly associated with CIN grade (p < 0.0001; Specificity = 0.93; Sensitivity = 0.68) than was the group of HPV types collectively classed as high-risk (p = 0.025; Specificity = 0.23; Sensitivity = 1.00).

Conclusions: These data suggest HPV testing specificity could be improved simply by including a separate test for HPV-16. In conjunction with previous studies, the data also suggests redefinition of the high-risk HPV category to take into account the differing degrees of oncogenicity of high-risk HPV types.

Human papillomavirus; Cervical intraepithelial neoplasia; ASCUS; Cervical screening

[1] Walboomers J.M.. Jacobs M.Y.. Manos M.M., Bosch F.X., Kummer J.A., Shah K.V. et al.: "Human papillomavirus is a neeessary cause of invasive cervical cancer worldwide". J. Pathol., 1999, 189, 12.

[2] Syrjanen K., Syrjanen S.: "Epidemiology of gen心1 HPV infeclions, CIN and cervical cancer". In: Syrjanen K., Syrjanen S., (eds.). "Papillomavirus Infections in Human Pathology" (1st ed.), New York: John Wiley & Sons, 2000, 117.

[3] Meijer C.J., Walboomers J.M.: "Cervical cytology after 2000 where to go?". J. Clin. Pathol., 2000, 53, 41.

[4] Schiffman M.H., Bauer H.M.. Hoover R.N., Glass A.G., Cadell D.M., Rush B.B. et al.: "Epidemiologic evidence showing that human papillomavirus infection causes most cervical intraepithelial neoplasia". J. Natl. Cancer Inst., 1993, 85, 958.

[5] Ostor A.G.: "Natural history of cervical intraepithelial neoplasia a critical review". Int. J. Gynecol. Pathol., 1993, 12, 186.

[6] The Atypical Squamous Cells of Undetermined Significance/LowGrade Squamous lntraepithelial Lesions Triage Study (ALTS) Group: "Human papillomavirus testing for triage of women with cytologic evidence of low-grade squamous intraepithelial lesions baseline data from a randomized trial". J. Natl. Cancer Inst., 2000, 92, 397.

[7] Kotloff K.L., Wasserman S.S., Russ K., Shapiro S., Daniel R., Brown W. et al.: "Detection of genital human papillomavirus and associated cytological abnormalities among college women". Sex Trans. Dis., 1998, 25, 243.

[8] Evans M.F., Mount S.L., Beatty B.G., Cooper K.: "Biotinyl-tyra mide-based in situ hybridization signal patterns distinguish human papillomavirus type and grade of cervical intraepithelial neoplasia". Mod. Pathol., 2002, 15, 1339.

[9] Jacobs M.V., Walboomers J.M., Snijders P.J., Voorhorst F.J., Verheijen R.H., Fransen-Daalmeijer N. et al.: "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.

[10] Matuskura T., Sugase M.: "Relationships between 80 human papillomavirus genotypes and different grades of cervical intraepithelial neoplasia: association and causality". Virology, 2001, 283, 139.

[11] Solomon D., Schiffman M., Tarone R.: "Comparison of three management strategies for patients with atypical squamous cells of undetermined significance: baseline results from a randomized trial". J. Natl. Cancer Inst., 2001, 93, 293.

[12] Bosch F.X., Manos M.M., Munoz N., Sherman M., Jansen A.M., Peto J. et aL."Prevalence of hu:11an papillomav.irus in cer:'ical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group". J. Natl. Cancer Inst., 1995, 87, 796.

[13] Lorincz A.T., Reid R., Jenson A.B., Greenberg M.D., Lancaster W., Kurman R.J.: "Human papillomavirus infection of the cervix: relative risk associations of 15 common anogenital types". Obstet. Gynecol., 1992.