Research
General gynecology
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

Presented at EUROGIN 2012, Prague, Czech Republic, July 8-11, 2011.
https://doi.org/10.1016/j.ajog.2012.11.020Get rights and content

Objective

The objective of the study was to compare 9 cervical cancer screening strategies to the current screening standard (cytology with human papillomavirus [HPV] triage of atypical squamous cells of undetermined significance) for the detection of high-grade cervical disease.

Study Design

Women (n = 34,254) aged 30 years or older from the Addressing the Need for Advanced HPV Diagnostics (ATHENA) study underwent screening with cytology and HPV testing with simultaneous HPV16/18 genotyping; those with atypical squamous cells of undetermined significance cytology or greater or HPV-positive status were referred for colposcopy.

Results

In general, screening strategies that offered greater sensitivity also required more referral to colposcopy. HPV testing was more sensitive than cytology for detection of cervical intraepithelial neoplasia grade 2 or greater, but strategies that depended on cytology for triage of HPV-positive women decreased this sensitivity. Various strategies of cotesting with cytology increased sensitivity but did so by increasing testing. Strategies that included integrated HPV16/18 testing provided more efficient referral to colposcopy.

Conclusion

Strategies that maximize detection of women at greatest risk of cervical intraepithelial neoplasia grade 3 or greater by immediate referral to colposcopy, with follow-up testing of women at intermediate risk, maximize the benefits of cervical cancer screening while decreasing the potential harm. Incorporating screening with HPV and triage of HPV-positive women by a combination of genotyping for HPV16/18 and cytology provided a good balance between maximizing sensitivity (benefit) and specificity by limiting the number of colposcopies (potential harm).

Section snippets

Study protocol

As previously described, the ATHENA HPV study enrolled more than 47,000 women aged 21 years and older who presented for cervical cancer screening; all eligible participants had both Papanicolaou testing (by liquid-based cytology, ThinPrep; Hologic, Bedford, MA) and HPV testing (by Amplicor HPV test, Linear Array high-risk HPV genotyping test, and the cobas HPV Test, all from Roche Molecular Systems).6 The protocol was approved by the institutional review boards at all study sites, and all women

Results

A total of 34,254 women aged 30 years or older were eligible for this analysis; the mean age was 44.7 years, and the demographics are shown in Table 1. Among the eligible women, 2872 (8.4%) tested positive with the cobas HPV Test, and 1966 (5.7%) had abnormal cytology; 280 women were diagnosed with CIN2 or more severe and 189 with CIN3 or more severe. The most sensitive screening strategy was screening with HPV alone (pooled 14 high-risk types) with referral of all HPV-positive women to

Comment

The ideal cervical cancer screening strategy would provide maximum sensitivity to minimize missing disease as well as maximum specificity to minimize false positive results and overreferral. Unfortunately, cervical cancer screening strategies that maximize both sensitivity and specificity have proven elusive because strategies that maximize sensitivity have typically produced relatively poor specificity. The development of invasive cervical cancer is typically a slow process that takes decades

Acknowledgments

We thank Teresa Wright, MD, for her valuable contributions to the design and execution of the ATHENA HPV Study and for assistance in the analysis of data. The ATHENA study testing sites and participants include the following: United States, Comprehensive Clinical Trials, West Palm Beach, FL; Green Clinic, Ruston, LA; Philadelphia Clinical Research, Philadelphia, PA; Visions Clinical Research, Boynton Beach, FL; Women's Health Specialist, Costa Mesa, CA; Mount Vernon Clinical Research, Atlanta,

References (23)

  • P.E. Castle et al.

    Performance of carcinogenic human papillomavirus (HPV) testing and HPV16 or HPV18 genotyping for cervical cancer screening of women aged 25 years and older: a subanalysis of the ATHENA study

    Lancet Oncol

    (2011)
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    This study was supported by Roche Molecular Systems.

    J.T.C. and P.E.C. are compensated for their services as members of a Data Monitoring Board for HPV vaccines for Merck. J.T.C. has received honoraria from Roche for assistance in the development of an educational slide set and for speaking on the cobas HPV Test. He has also received honoraria for service on the scientific advisory board for Gen-Probe and advisory boards for Graceway and Bradley Pharmaceuticals. P.E.C. has received HPV tests and testing for research at a reduced or no cost from Roche and Qiagen. T.C.W. is compensated for his services as a reference pathologist, clinical adviser, and speaker for Roche, Gen-Probe, BD Diagnostics, and Ikonisys. He has received honoraria for serving on a scientific advisory board for HPV vaccines for Merck. J.C. has served on advisory boards for Roche, Gen-Probe, Abbott, and Qiagen. C.M.B. and A.S. are employees of Roche Molecular Systems.

    Cite this article as: Cox JT, Castle PE, Behrens CM, et al. 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 2013;208:184.e1-11.

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