Tests of Low-Risk HPV Types Fail to Detect Later Cancer Risk

Diedtra Henderson

January 02, 2014

Testing for low-risk human papillomavirus (HPV) types should be excluded from cervical cancer screening because such tests fail to predict risk of developing cervical intraepithelial neoplasia (CIN) grade 3 or worse, as well as expose women to potential harm; in addition, they have no proven benefit for patients, according to 2 large studies.

Both reports were published in the January 2014 issue of Obstetrics & Gynecology.

In the first report, a prospective cohort study led by Louise T. Thomsen, MSc, from the Unit of Virus, Lifestyle, and Genes, Danish Cancer Society Research Center, Copenhagen, the researchers tested liquid-based cervical cytology samples provided by 35,539 women screened for cervical cancer in Copenhagen from 2002 to 2005 for 13 high-risk and 5 low-risk HPV types.

Cervical cancer screening has been credited with paring the incidence rate of cancer in developed countries, but the ubiquitous testing comes with a downside: Up to 31% of US providers routinely conduct low-risk screening, contrary to guidelines that discourage such testing. Thomsen and colleagues sought to tease out the ability of low-risk HPV screening to predict cervical cancer risk.

Of the participants, 1218 women (3.4%) had low-risk HPV alone; their median age was 32 years. Another 6105 women (17.2%) had just high-risk HPV; their median age was 38 years. The majority of the patients, 26,981 (75.9%), were negative for both high- and low-risk HPV types.

Among women younger than 30 years, the absolute risk for CIN 3 or worse was lower for those who were high-risk HPV-negative than for those with normal baseline cytology at 3, 5, and 8 years of follow-up. In addition, for women aged 30 years or older, a negative high-risk HPV test "gave greater reassurance against CIN 3 or worse than a normal cytology result" at 3, 5, and 8 years of follow-up, according to the researchers.

"Our results support current recommendations that screening for cervical cancer should not include testing for low-risk HPV types. Screening for HPV types unrelated to cervical cancer may cause improper follow-up procedures, waste of resources, and unnecessary psychological distress for patients," Thomsen and colleagues write.

In the second study, led by Philip E. Castle, PhD, MPH, from the Albert Einstein College of Medicine, New York City, researchers conducted HPV genotyping on 59,644 residual cervical cytology specimens contained in the New Mexico Human Papillomavirus Pap Registry. Detecting HPV 6, 11, 42, or some combination of the 3 low-risk types did not identify women with heightened 3-year risk for cervical precancer.

Dr. Castle and colleagues argue for removing tests for HPV types 6, 11, 42, or combinations from cervical cancer prevention programs and discontinuing commercial tests that target these genotypes.

"HPV prevalence is greatest in young reproductive-aged women, those who might experience the greatest harms of low-risk HPV testing," Dr. Castle and coauthors note. "Therefore, testing for low-risk HPV 6, 11, 42, or combinations of these types (or related types such as HPV 43 and 44) should be strongly discouraged to reduce the potential harms resulting from unnecessary testing and to conserve health care resources needed for other services that do benefit to patients."

Obstetrics & Gynecology Editor-in-Chief Nancy C. Chescheir, MD, said in a podcast that clinicians could pressure vendors to remove the low-risk HPV types from the testing bundle and added that clinicians could work with cytology partners to use high-risk HPV programs only.

Both studies, conducted in separate populations, show that "we need to stop doing the low-risk HPV testing because it does drive problems for patients and doctors. If we come up with these results, we have to do something with them," Dr. Chescheir said. "Clearly having to explain to women that 'Yes, they have this virus in their systems or evidence of it in their systems, but it's not significant' becomes very difficult to convince women that low-risk means low-risk and it's really nothing to worry about."

Financial support for the first study was provided by the Danish Cancer Society, the MERMAID 2 project, and Sanofi Pasteur MSD. Four coauthors disclosed receiving funding or speakers' fees from Sanofi Pasteur MSD and receiving funding from or serving as a paid consultant for Merck. One author also disclosed serving as a paid consultant for BD, Cepheid, GE Healthcare, GenProbe/Hologic, and Roche and receiving HPV tests and reagents at reduced or no cost from mtm, Norchip, Qiagen, and Roche. Another author disclosed receiving pass-through funding from Hologic GmbH and Roche Diagnostics GmBH. One author has disclosed no relevant financial relationships. Financial support for the second study was provided by the National Institutes of Health. One author disclosed receiving HPV tests and testing at a reduced or no cost from Qiagen and Roche, funding from Merck, and serving as a paid consultant for BD, Cepheid, Gen-Probe, and Roche. A second author disclosed receiving pass-through funding from the National Institutes of Health, funding from GlaxoSmithKline, and travel reimbursement from Roche Molecular Systems. The other authors have disclosed no relevant financial relationships.

Obstet Gynecol. 2014;123:49-64. Thomsen full text, Castle abstract


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