This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (139)  • Contact me when this article is cited  Related Content  • Similar articles in JAMA  Topic Collections  • Genetic Counseling/ Testing/ Therapy  • Gynecology  • Women's Health, Other  • Oncology  • Cervical Cancer  • Papillomavirus, Human  • Alert me on articles by topic

Comparison of Sensitivity, Specificity, and Frequency of Referral

Shalini L. Kulasingam, PhD; James P. Hughes, PhD; Nancy B. Kiviat, MD; Constance Mao, MD; Noel S. Weiss, MD, DrPH; Jane M. Kuypers, PhD; Laura A. Koutsky, PhD

JAMA. 2002;288:1749-1757.

Context  Human papillomavirus (HPV) DNA testing of women having Papanicolaou (Pap) smears showing atypical squamous cells of undetermined significance (ASCUS) has clinical usefulness. Whether HPV DNA testing alone is useful in primary screening remains to be determined.

Objective  To determine the accuracy of HPV DNA testing for detecting cervical intraepithelial neoplasia (CIN) grade 3 or cancer (the criterion standard).

Design, Setting, and Participants  Between December 1997 and October 2000, 4075 women who attended Planned Parenthood clinics in Washington State were screened simultaneously using thin-layer Pap and HPV DNA testing by a polymerase chain reaction (PCR)–based method and by a liquid-based RNA-DNA hybridization capture with signal amplification assay (signal amplification). Women who were positive for high-risk HPV types, or had Pap results of ASCUS or higher, were considered to have positive screening test results and were referred for colposcopy and biopsy. Additionally, a random sample of women with negative screening test results was referred for colposcopy. Based on individual and combined thin-layer Pap, HPV PCR, and HPV signal amplification test results from the screening and the colposcopy visits, 7 colposcopy triage strategies were defined and evaluated.

Main Outcome Measure  Sensitivity and specificity for detecting cervical lesions graded CIN 3 or higher for each of the 7 triage strategies.

Results  The estimated prevalence of CIN 3 or higher was 3.2%. The sensitivity (95% confidence interval) of thin-layer Pap (with a result of ASCUS) for identifying women with CIN 3 or higher was only 61.3% (48.5%-70.9%) compared with 88.2% (78.9%-93.8%) for HPV testing by PCR and 90.8% (83.1%-95.8%) by signal amplification. Differences in specificities were also observed: 82.4% (81.8%-83.1%) for thin-layer Pap (with a result of ASCUS), 78.8% (77.9%-79.7%) for PCR, and 72.6% (69.4%-75.0%) for signal amplification. Compared with referral for colposcopy of all women with ASCUS or higher, signal amplification testing of women with ASCUS and referral of those with a positive result was about as sensitive (61.3% vs 60.3%, respectively) and significantly more specific (82.4% vs 88.9%, respectively). The strategy requiring repeat positive PCR tests on 2 visits had a sensitivity of 84.2% (75.3%-91.0%) and a specificity of 86.2% (85.1%-87.3%). All tests were more specific and less sensitive in older (30 years) vs younger women.

Conclusions  Testing for HPV has higher sensitivity but lower specificity than thin-layer Pap screening. In some settings, particularly where screening intervals are long or haphazard, screening for HPV DNA may be a reasonable alternative to cytology-based screening of reproductive-age women.

Author Affiliations: Departments of Epidemiology (Drs Kulasingam, Weiss, and Koutsky), Biostatistics (Dr Hughes), Pathology (Drs Kiviat and Kuypers), and Obstetrics and Gynecology (Dr Mao), University of Washington, Seattle. Dr Kulasingam is now with the Department of Obstetrics and Gynecology, Duke University, Durham, NC.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Persistent Human Papillomavirus Infection and Cervical Neoplasia: A Systematic Review and Meta-Analysis
Koshiol et al.
Am J Epidemiol 2008;168:123-137.
ABSTRACT | FULL TEXT  

Invited Commentary: Is Monitoring of Human Papillomavirus Infection for Viral Persistence Ready for Use in Cervical Cancer Screening?
Castle
Am J Epidemiol 2008;168:138-144.
ABSTRACT | FULL TEXT  

Results at Recruitment From a Randomized Controlled Trial Comparing Human Papillomavirus Testing Alone With Conventional Cytology as the Primary Cervical Cancer Screening Test
Ronco et al.
JNCI J Natl Cancer Inst 2008;100:492-501.
ABSTRACT | FULL TEXT  

Human Papillomavirus Infection and Cervical Cytology in Women Screened for Cervical Cancer in the United States, 2003-2005
Datta et al.
ANN INTERN MED 2008;148:493-500.
ABSTRACT | FULL TEXT  

Comparison of Linear Array and Line Blot Assay for Detection of Human Papillomavirus and Diagnosis of Cervical Precancer and Cancer in the Atypical Squamous Cell of Undetermined Significance and Low-Grade Squamous Intraepithelial Lesion Triage Study
Castle et al.
J. Clin. Microbiol. 2008;46:109-117.
ABSTRACT | FULL TEXT  

Human Papillomavirus DNA versus Papanicolaou Screening Tests for Cervical Cancer
Mayrand et al.
NEJM 2007;357:1579-1588.
ABSTRACT | FULL TEXT  

Promoter Hypermethylation of Tumor Suppressor Genes in Urine from Patients with Cervical Neoplasia
Feng et al.
Cancer Epidemiol. Biomarkers Prev. 2007;16:1178-1184.
ABSTRACT | FULL TEXT  

A Cross-sectional Study of a Prototype Carcinogenic Human Papillomavirus E6/E7 Messenger RNA Assay for Detection of Cervical Precancer and Cancer
Castle et al.
Clin. Cancer Res. 2007;13:2599-2605.
ABSTRACT | FULL TEXT  

Modeling Human Papillomavirus Vaccine Effectiveness: Quantifying the Impact of Parameter Uncertainty
Van de Velde et al.
Am J Epidemiol 2007;165:762-775.
ABSTRACT | FULL TEXT  

American Cancer Society Guideline for Human Papillomavirus (HPV) Vaccine Use to Prevent Cervical Cancer and Its Precursors
Saslow et al.
CA Cancer J Clin 2007;57:7-28.
ABSTRACT | FULL TEXT  

Pilot Study of a Commercialized Human Papillomavirus (HPV) Genotyping Assay: Comparison of HPV Risk Group to Cytology and Histology
Castle et al.
J. Clin. Microbiol. 2006;44:3915-3917.
ABSTRACT | FULL TEXT  

Human papillomavirus testing and liquid-based cytology: results at recruitment from the new technologies for cervical cancer randomized controlled trial.
Ronco et al.
JNCI J Natl Cancer Inst 2006;98:765-774.
ABSTRACT | FULL TEXT  

Prevention of cervical cancer through vaccination of adolescents.
Pichichero
CLIN PEDIATR 2006;45:393-398.
 

Comparison between the Hybrid Capture II Test and an SPF1/GP6+ PCR-Based Assay for Detection of Human Papillomavirus DNA in Cervical Swab Samples.
Huang et al.
J. Clin. Microbiol. 2006;44:1733-1739.
ABSTRACT | FULL TEXT  

Cost-effectiveness analysis of liquid-based cytology and human papillomavirus testing in cervical cancer screening.
Bidus et al.
Obstet Gynecol 2006;107:997-1005.
ABSTRACT | FULL TEXT  

Discovery of Novel Methylation Biomarkers in Cervical Carcinoma by Global Demethylation and Microarray Analysis
Sova et al.
Cancer Epidemiol. Biomarkers Prev. 2006;15:114-123.
ABSTRACT | FULL TEXT  

A 21-Year-Old Woman With Atypical Squamous Cells of Undetermined Significance
Sawaya
JAMA 2005;294:2210-2218.
FULL TEXT  

Acceptability of human papillomavirus self testing in female adolescents
Kahn et al.
Sex. Transm. Infect. 2005;81:408-414.
ABSTRACT | FULL TEXT  

Human Papillomavirus Genotype Distribution in Low-Grade Cervical Lesions: Comparison by Geographic Region and with Cervical Cancer
Clifford et al.
Cancer Epidemiol. Biomarkers Prev. 2005;14:1157-1164.
ABSTRACT | FULL TEXT  

Atypical Squamous Cells of Undetermined Significance: Human Papillomavirus Testing in Adolescents
Boardman et al.
Obstet Gynecol 2005;105:741-746.
ABSTRACT | FULL TEXT  

Incidence of Cervical Squamous Intraepithelial Lesions Associated With HIV Serostatus, CD4 Cell Counts, and Human Papillomavirus Test Results
Harris et al.
JAMA 2005;293:1471-1476.
ABSTRACT | FULL TEXT  

Detection of Hypermethylated Genes in Women with and Without Cervical Neoplasia
Feng et al.
JNCI J Natl Cancer Inst 2005;97:273-282.
ABSTRACT | FULL TEXT  

Facile, Comprehensive, High-Throughput Genotyping of Human Genital Papillomaviruses Using Spectrally Addressable Liquid Bead Microarrays
Wallace et al.
J. Mol. Diagn. 2005;7:72-80.
ABSTRACT | FULL TEXT  

Self-testing for human papillomavirus using a vaginal swab: placing prevention of cervical cancer in the patient's hands
Kahn
Ann Oncol 2004;15:847-849.
FULL TEXT  

Cigarette Smoking, Oncogenic Human Papillomavirus, Ki-67 Antigen, and Cervical Intraepithelial Neoplasia
Harris et al.
Am J Epidemiol 2004;159:834-842.
ABSTRACT | FULL TEXT  

Detecting Cervical Cancer by Quantitative Promoter Hypermethylation Assay on Cervical Scrapings: A Feasibility Study
Reesink-Peters et al.
Mol Cancer Res 2004;2:289-295.
ABSTRACT | FULL TEXT  

Projected Clinical Benefits and Cost-effectiveness of a Human Papillomavirus 16/18 Vaccine
Goldie et al.
JNCI J Natl Cancer Inst 2004;96:604-615.
ABSTRACT | FULL TEXT  

Interim Guidance for the Use of Human Papillomavirus DNA Testing as an Adjunct to Cervical Cytology for Screening
Wright et al.
Obstet Gynecol 2004;103:304-309.
ABSTRACT | FULL TEXT  

Risk of Cervical Cancer Associated with Extending the Interval between Cervical-Cancer Screenings
Sawaya et al.
NEJM 2003;349:1501-1509.
ABSTRACT | FULL TEXT  

A Comparison of Single and Combined Visual, Cytologic, and Virologic Tests as Screening Strategies in a Region at High Risk of Cervical Cancer
Ferreccio et al.
Cancer Epidemiol. Biomarkers Prev. 2003;12:815-823.
ABSTRACT | FULL TEXT  

Ki-67 immunocytochemistry in liquid based cervical cytology: useful as an adjunctive tool?
Sahebali et al.
J. Clin. Pathol. 2003;56:681-686.
ABSTRACT | FULL TEXT  

Potential Health and Economic Impact of Adding a Human Papillomavirus Vaccine to Screening Programs
Kulasingam and Myers
JAMA 2003;290:781-789.
ABSTRACT | FULL TEXT  

Invited Commentary
Siegelman
RadioGraphics 2003;23:981-981.
FULL TEXT  

Human Immunodeficiency Virus Infection: A Focus on Women
Pakyz et al.
Journal of Pharmacy Practice 2003;16:170-181.
ABSTRACT  

Chapter 13: Primary Screening of Cervical Cancer With Human Papillomavirus Tests
Franco
J Natl Cancer Inst Monogr 2003;2003:89-96.
ABSTRACT | FULL TEXT  

OTHER ARTICLES NOTED (25 Oct 02 to 17 Jan 03)
Evid. Based Nurs. 2003;6:e1-7.
FULL TEXT  

ABSTRACTS
Obstet Gynecol 2003;101:612-615.
FULL TEXT  

The Search for the Perfect Cervical-Abnormality Screen
JWatch Women's Health 2002;2002:7-7.
FULL TEXT  

A Controlled Trial of a Human Papillomavirus Type 16 Vaccine
Koutsky et al.
NEJM 2002;347:1645-1651.
ABSTRACT | FULL TEXT