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Human papillomavirus (HPV) messenger RNA (mRNA) assays may be less sensitive at detecting latent HPV infections, as women who previously tested positive for HPV via a DNA test then tested negative with mRNA testing, a quality-improvement study found.

There was an almost 70% difference in HPV mRNA testing compared with previous HPV DNA testing, including a potential change in follow-up for over 70% of patients, reported Sarah Cotton, of McGovern Medical School at the University of Texas Health Science Center at Houston, and colleagues.

Writing in , the authors noted that HPV DNA testing can tell if HPV infection is present or absent, but cannot detect the difference between an active and latent infection. "Compared with the DNA assay, the mRNA assay is more specific in predicting the presence of dysplasia, but less sensitive in detecting the presence of latent HPV infection," the researchers explained.

"Based on these data and the potential change in follow-up care, the HPV mRNA screening assay should not be used for a primary screening tool for cervical cancer. Many pathology laboratories have shifted to using the HPV mRNA assay without clear discussion with gynecologists about the effects on patient follow-up."

Cotton et al noted that they observed this distinction firsthand when they were enrolling patients for an HPV research study and found that "multiple patients" with over 10 years of history of high-risk HPV positivity now had a negative test. Upon further investigation, the team found that the collaborating pathology laboratory had recently switched from an HPV DNA assay to an HPV mRNA assay.

Commenting on the study, the journal's editor, Nancy Chescheir, MD, said on an accompanying podcast that the point of the study was not to examine both tests from a virology perspective, but rather that clinicians "have to know what their lab is doing, what test they're doing, what the limits of those tests are, and that you'll be able to use the correct test for the question you're asking."

The researchers examined data from November 2014 to June 2016 for women ages 30 and older with more than one HPV-positive result, which included one or more HPV mRNA assay result and one or more HPV DNA assay result, from a pathology laboratory software database. That particular age range was used intentionally, the team explained, because older age is associated with a greater likelihood of a persistent HPV infection.

Overall, the investigators looked at 425 patient pathology charts. A total of 289 patients (68%) had a negative mRNA test following a positive DNA test for HPV. Notably, 69.6% of patients with discordant results would potentially have a change in follow-up, as recommended by the American College of Obstetricians and Gynecologists (ACOG) 2016 Follow-up was potentially altered in 71.7% of patients with one prior HPV DNA-positive screening, and in 59.6% of patients with at least two prior HPV DNA test results.

Of the 231 available colposcopy reports, about a quarter had abnormal results, including 45 low-grade squamous intraepithelial lesion diagnoses, 15 high-grade squamous intraepithelial lesion diagnoses, and two cancer diagnoses. The authors noted that about 40% of these abnormal colposcopy findings were in patients with a history of at least two prior HPV DNA-positive results and a report of being HPV negative with an mRNA assay.

The main limitation of the study, Cotton et al wrote, was that the samples were not tested simultaneously using both the HPV mRNA and HPV DNA assays.

Chescheir said there was some concern that the authors may have "overstretched their data in the results" about the two tests, but that the point of the research was not the accuracy of the two tests, but how clinical care could change based on the test used, which clinicians may not even be aware of.

"This could change clinical practice, if 'practice' is 'I'm a doc, I'm going to find out what the test is' -- that is the point of this paper," she said.