A better test for human papillomavirus

"This is important because reducing false positive results avoids unnecessary additional tests and follow-up, the associated health care costs, and distress to women," says first author Sam Ratnam, of the Faculty of Medicine, Memorial University, St. John's, Newfoundland and Labrador. HPV infection, he explains, is highly prevalent, but "only a small fraction of the infected are at risk of developing HPV-associated cancers."

The investigators report that the new test, called the Aptima HPV test, detected 96.3 percent of women with high-grade cervical intraepithelial neoplasia or worse (CIN 2+) compared to 94.3 percent for the old test, the Hybrid Capture 2 DNA test (HC2), among 1418 women studied. But Aptima has far fewer false positives than HC2. "This difference could be attributed to the fact that the Aptima test detects the expression of two oncogenes, E6 and E7, via their messenger RNAs," says Ratnam. "These proteins are involved in initiation and mediation of oncogenic process that leads to cervical cancer, and to other HPV-associated cancers. The HC2 test, on the other hand, detects the viral DNA which is not as discriminating. The Pap smear, the traditional common screening method for cervical cancer, has few false positives, but fails to detect nearly half of all CIN 2+ cases."

While HPV is the single most common sexually transmitted virus, its spread is increasing due to rising oral sex among young people, according the Oral Cancer Foundation. "We're seeing more and more cases of tonsilar cancers in Newfoundland," a cancer which is frequently caused by HPV, says coauthor Adrian Lear of the Dr. H. Bliss Murphy Cancer Centre, St. John's, Newfoundland. In people under the age of 50, HPV-associated oral cancers may even be replacing tobacco as the primary causative agent according to the Oral Cancer Foundation.

While the role of HPV is most recognized in cervical cancer, it is also associated with anal and penile cancers, and cancers of the vagina and vulva. The test could detect HPV infections that have begun to progress towards these other HPV-associated cancers, says Ratnam.

Currently, two vaccines are available against HPV: Gardasil, which is active against four types, 16, 18, 6 and 11, and Cerverix, which is active against two types, 16 and 18. Types 16 and 18 account for about 70% cervical cancer world-wide, and types 6 and 11 account for over 90% of genital warts. These vaccines are now approved in many countries around the world but offered only to females. "I'm convinced the day is coming when the vaccine will be offered for both males and females through publicly funded programs," says Lear. "In the meantime, the use of a more accurate test such as the Aptima test should improve the efficiency and cost-effectiveness of cervical cancer screening around the world, and should help prevent cervical cancer," says Ratnam.

(Samuel Ratnam, Francois Coutlee, Dan Fontaine, James Bentley, Nicholas Escott, Prafull Ghatage, Veeresh Gadag, Glen Holloway, Elias Bartellas, Nick Kum, Christopher Giede, and Adrian Lear. 2011. Aptima HPV E6/E7 mRNA Test Is as Sensitive as Hybrid Capture 2 Assay but More Specific at Detecting Cervical Precancer and Cancer. J. Clin. Microbiol. 49: 557-564.)