Should the HPV Test Be Used as a First-Line Primary Cervical Cancer Screen?

The benefits and validity of high-risk HPV (HR-HPV) testing alone or in combination with cytology have been studied and debated over the past several years.

In the past, several randomized clinical trials (RCTs) have been performed to assess screening with hrHPV testing alone and in combination with cytology. Many of these RCTs have lent support to the use of the HPV test as the primary screening test for cervical cancer. However, some scientific experts were not convinced that the HPV test should be used for that purpose. In addition, most professional organizations prior to 2018 did not issue recommendations for using the HPV test alone for cervical cancer screening. The following is a summary of the RCTs used to assess the HPV test:

Several RCTs have been performed to assess screening with HR-HPV testing alone vs. cytology alone. These trials studied the accuracy of the Cobas HPV test performed on prospectively collected cervical/endocervical samples in ThinPrep media and tested using the Digene Hybrid Capture 2 High-Risk HPV DNA test and the Roche Cobas HPV test. The overall average agreement between the two tests was 91%. In addition, the test was compared to the colposcopy results and demonstrated a sensitivity of 91% and specificity of 31%. Compared to the results of a tissue biopsy diagnosis, the Cobas HPV test was found to have a sensitivity of 52% and specificity of 87%.

Two independent studies have been conducted in recent years that evaluated cytology, co-testing, and primary HPV screening. The Kaiser Permanente Northern California (KPNC) study was published in 2011, and the Addressing THE Need for Advanced HPV Diagnostics (ATHENA) trial, which evaluated the performance of the Cobas HPV test, was conducted several years later. If you would like further details regarding the KPNC study and the ATHENA trial, please review the PDF documents included on this page.

While the ATHENA and Kaiser Studies, as well as the FDA approval for the Cobas HPV test, lend support to the use of the HPV test as the primary screening test for cervical cancer, some scientific experts were not yet convinced that the HPV test should be used for that purpose. Some think co-testing with the PAP test may be better since a clinician may discover more disease than if the HPV test is employed as the sole test. In the June 2014 CAP TODAY lead article entitled “Data spark new directions in cervical cancer," Dr. William Check presented an extensive review of the clinical data supporting the use of the HPV test as a primary screen for cervical cancers. In addition, the article pointed out the reservations from other experts about the use of the HPV test as a primary algorithm for cervical cancer screening, citing still unanswered issues and questions about the test as well as a need for professional groups to evaluate the data.³

Overall, these RCTs found that hrHPV testing alone led to an increase in the rate of CIN 3 detection compared with cytology alone. The primary conclusions in the RCTs were that the total number of follow-up tests, number of colposcopies, and false positive rates were increased. Although follow-up tests and colposcopies are essential for detecting cervical cancer, they also represent a risk and burden to patients and may produce downstream harm. Some experts have concluded that screening strategies for cervical cancer should serve to avert or at least minimize the number of tests and colposcopies per cancer case.