HPV DNA testing in cervical cancer screening: results from women in a high-risk province of Costa Rica

JAMA. 2000 Jan 5;283(1):87-93. doi: 10.1001/jama.283.1.87.

Abstract

Context: Human papillomaviruses (HPVs) are known to cause most cervical cancer worldwide, but the utility of HPV DNA testing in cervical cancer prevention has not been determined.

Objective: To provide comprehensive data on the screening performance of HPV testing for the most common carcinogenic types, at different levels of analytic sensitivity.

Design: Laboratory analysis conducted during 1993-1995, using 3 cytologic techniques and cervicography, followed by colposcopic examination of women with any abnormal cervical finding, to detect all high-grade intraepithelial lesions and cancer (reference standard of clinically significant disease). The HPV testing was performed subsequently with masking regarding clinical findings.

Setting: Guanacaste Province, Costa Rica, a region with a high age-adjusted incidence of cervical cancer.

Participants: Of 11742 randomly selected women, 8554 nonpregnant, sexually active women without hysterectomies underwent initial HPV DNA testing using the original Hybrid Capture Tube test; a stratified subsample of 1119 specimens was retested using the more analytically sensitive second generation assay, the Hybrid Capture II test.

Main outcome measures: Receiver operating characteristic analysis of detection of cervical high-grade intraepithelial lesions and cancer by HPV DNA testing based on different cut points of positivity.

Results: An analytic sensitivity of 1.0 pg/mL using the second generation assay would have permitted detection of 88.4% of 138 high-grade lesions and cancers (all 12 cancers were HPV-positive), with colposcopic referral of 12.3% of women. Papanicolaou testing using atypical squamous cells of undetermined significance as a cut point for referral resulted in 77.7% sensitivity and 94.2% specificity, with 6.9% referred. Specificity of the second generation assay for positivity for high-grade lesions and cancer was 89.0%, with 33.8% of remaining HPV DNA-positive subjects having low-grade or equivocal microscopically evident lesions. The higher detection threshold of 10 pg/mL used with the original assay had a sensitivity of 74.8% and a specificity of 93.4%. Lower levels of detection with the second generation assay (<1 pg/mL) proved clinically nonspecific without gains in diagnostic sensitivity.

Conclusions: In this study population, a cut point of 1.0 pg/mL using the second generation assay permitted sensitive detection of cervical high-grade lesions and cancer, yielding an apparently optimal trade-off between high sensitivity and reasonable specificity for this test. The test will perform best in settings in which sensitive detection of high-grade lesions and cancer is paramount. Because HPV prevalence varies by population, HPV testing positive predictive value for detection of high-grade lesions and cancer will vary accordingly, with implications for utility relative to other cervical cancer screening methods.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Cervical Intraepithelial Neoplasia / diagnosis
  • Cervical Intraepithelial Neoplasia / prevention & control*
  • Cervical Intraepithelial Neoplasia / virology
  • Colposcopy
  • Costa Rica
  • DNA, Viral / analysis*
  • Female
  • Humans
  • Mass Screening* / methods
  • Middle Aged
  • Papanicolaou Test
  • Papillomaviridae / genetics
  • Papillomaviridae / isolation & purification*
  • Papillomavirus Infections / diagnosis*
  • Sensitivity and Specificity
  • Tumor Virus Infections / diagnosis*
  • Uterine Cervical Neoplasms / diagnosis
  • Uterine Cervical Neoplasms / prevention & control*
  • Uterine Cervical Neoplasms / virology
  • Vaginal Smears

Substances

  • DNA, Viral