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HPV-16, -18 Testing Outperforms Cytology : Liquid-based cytology added little to cobas HPV testing for detecting CIN 3 or worse.


 

From Lancet Oncology

Major Finding: The cobas HPV test was significantly more sensitive for detecting CIN 3 or worse than was liquid-based cytology at a threshold of ASCUS or worse (92% vs. 53.3%). Adding cytology to HPV testing increased the sensitivity for detection of CIN 3 or worse by less than 5% (from 92% to 96.7%), but increased the number of screen positives by more than 35%.

Data Source: A subanalysis of the ATHENA study population to compare the screening performance of the cobas HPV test versus liquid-based cytology for cervical cancer screening.

Disclosures: The study was funded by Roche Molecular Systems. Dr. Castle said he has a nondisclosure agreement to work with Roche on the analysis of their clinical trial but receives no financial compensation. Other authors on the study disclosed that they are employed by Roche Molecular Systems and/or have stock or stock options in the company, or that they have received consulting fees, honoraria, and/or other compensation from Roche, BD Diagnostics, Qiagen, Gen-Probe, Ventana, and/or Merck.

Cobas human papillomavirus testing with individual human papillomavirus types 16 and 18 detection could serve as a more sensitive and more efficient approach to cervical cancer screening than traditional liquid-based cytology methods alone, according to a subanalysis of data from the ATHENA study.

The findings of the current analysis have implications for the development of strategies – including triage to colposcopy – for managing HPV-positive women, according to Philip E. Castle, Ph.D., of the American Society for Clinical Pathology Institute, Washington, and his colleagues.

The investigators analyzed data from 41,955 women aged 25 years and older who were part of the ATHENA (Addressing the Need for Advanced HPV Diagnostics) study, which was designed to assess the performance of HPV testing and HPV-16 and HPV-18 genotyping, compared with liquid-based cytology for cervical cancer screening. Of 40,901 women who had valid cobas HPV and liquid-based cytology test results available, 10% (4,275) tested HPV positive and 6% (2,617) had abnormal cytology; of these, 1.1 % (431) were diagnosed with cervical intraepithelial neoplasia grade 2 (CIN 2) or worse, and 0.7% (274) were diagnosed with CIN 3 or worse.

An analysis of the results of colposcopy, which was performed in 2,609 women found to have atypical squamous cells of undetermined significance (ASCUS) or worse cytology, 5,726 women with a positive HPV test by either of the first-generation HPV DNA assays used in the study (Amplicor HPV test and Linear Array HPG genotyping), and 1,041 women who were HPV negative and who had negative for intraepithelial or malignant (NILM) cervical cytology, showed that the cobas HPV test was significantly more sensitive for detecting CIN 3 or worse than was liquid-based cytology at a threshold of ASCUS or worse (92% vs. 53.3%), according to the investigators (Lancet Oncol. 2011; 12:880-90).

The addition of cytology to HPV testing increased the sensitivity for detection of CIN 3 or worse by less than 5% (from 92% to 96.7%), but increased the number of screen positives by more than 35%, Dr. Castle and his associates said.

When used as a triage test for identifying high-grade CIN (grade 3 or higher), the detection of HPV-16, HPV-18, or both alone was statistically equivalent to the detection of ASCUS or worse alone in terms of both sensitivity (59.5% and 52.8%, respectively) and positive predictive value (15.5% and 14.1%), they noted.

Sensitivity was further increased – and the positive predictive value (PPV) decreased – by use of HPV-16, HPV-18, or both as an additional or complementary triage strategy to ASCUS or worse, they said.

The authors added that “notably, testing positive for HPV-16, HPV-18, or both had a sensitivity of 53.8% … and [a] PPV of 10.2% … for CIN 3 or worse in women aged 25 years or older who were HPV positive and had NILM cytology.”

In addition, the use of a threshold of low-grade squamous intraepithelial lesion (LSIL) or worse with HPV-16, HPV-18, or both was more sensitive than detection of ASCUS or worse alone with similar PPV, and detection of high-grade squamous intraepithelial lesion (HSIL) or worse with HPV-16, HPV-18, or both had a higher sensitivity and PPV than ASCUS or worse alone.

The study findings suggest that that the use of HPV testing as the primary screening test to rule out cervical disease, along with a specific test such as liquid-based cytology to help determine which women should be sent for immediate colposcopy, is a rational approach.

The findings also support the premise that co-testing has little benefit over HPV testing alone, the investigators noted.

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