USPSTF: Evidence supports cytology as primary screen for cervical cancer

Whitlock EP. Ann Intern Med. 2011 [Published online ahead of print Oct. 17].

In an update to guidelines first issued in 2003, members of the US Preventive Services Task Force said liquid-based or conventional cytology appear to be equally effective as a screen for cervical cancer in women aged at least 30 years, but HPV screening was too likely to generate false-positive results to serve as a substitute for the other tests.

HPV screening, with or without cytology triage, appears to be more sensitive but less specific, and it is still unclear how much HPV screening improves early disease detection, according to a report published online.

“Although HPV-enhanced screening strategies offer a potential cancer prevention benefit compared with cytology alone, test performance studies alone are insufficient to justify substituting HPV testing for cytology,” Evelyn P. Whitlock, MD, MPH, of the Oregon Evidence-based Practice Center, and colleagues wrote. “Thus, experts agree that large, pragmatic, comparative randomized, controlled trials of repeated screening rounds are necessary, with increasing emphasis on the need to confirm the effect, not just on surrogates (such as cervical intraepithelial neoplasia) but also on cancer incidence and mortality.”

Whitlock and colleagues concluded that HPV screening is promising, but not yet ready for wide use. Maurie Markman, MD, senior vice president of clinical affairs and national director of medical oncology for Cancer Treatment Centers of America, and gynecologic cancer section editor for HemOnc Today, took a similar position.

Maurie Markman
Maurie
Markman

“Long-term follow-up is important,” Markman said. “We’ll learn more in the future about more detailed nomograms on how to use the test.”

Whitlock and colleagues reviewed 4,262 abstracts and 641 full-text articles published from September 2010 to August. They also added nine additional studies to the review. Researchers identified one fair-quality and one good-quality randomized controlled trial comprising 134,162 women aged 30 to 60 years. The review also included two fair-quality observational studies of 7,404 similarly aged women who reported absolute sensitivity and specificity of both tests in primary care applicable settings.

Based on these results, liquid-based cytology and conventional cytology were roughly equal for relative detection, absolute sensitivity and specificity for detection of cervical intraepithelial neoplasia (CIN) 2+/CIN3+ at any cytologic threshold.

Results from six diagnostic accuracy studies showed that one-time HPV testing was more sensitive but less specific than cytology. For CIN3+ outcomes, point estimates for sensitivity ranged from 86% to 97% for HPV testing compared with 46% to 50% for cytology. Sensitivity ranged from 63% to 98% for HPV testing vs. 38% to 65% for cytology of CIN2+ outcomes. However, the task force said specificity for CIN2+ and CIN3+ was consistently 3% to 5% lower for HPV testing. In one Italian study, more than twice as many women who underwent HPV screening were referred to colposcopy (5.8% vs. 2.5%).

Researchers conducting four large trials — ARTISTIC, NTCC phase 1, POBASCAM and Swedescreen — involving 82,390 participants compared cytology screening alone vs. cytology plus HPV screening. Cumulative CIN 3+ detection was the same between combination testing and cytology alone after two screening rounds in all four trials. Cumulative invasive cancer detection was similar or slightly higher for cytology alone than for the combination in all trials, except ARTISTIC.

NTCC phase 1 was the only trial to show a relative increase in any cumulative CIN measure after combination testing, but that trial used a lower threshold for immediate colposcopy than the other trials. In the other three trials, high-grade squamous intraepithelial lesion was the referral threshold for colposcopy, with colposcopy referral for HPV-positive results only after repeated testing revealed persistent HPV positivity or abnormal cytology, according to the report.

“Many doctors in the United States are doing cytology along with HPV. It’s not that expensive and if there’s an abnormal cytology but abnormal HPV, it’s considered a negative result,” Markman said. “The problem with cytology is that it can be very non-specific, and of course, the problem with HPV is that it can be non-specific as well. But the combination of an abnormal cytology and an abnormal potentially high-risk HPV is very powerful. One cannot make the argument today that it’s terribly cost-effective, but I think it’s a reasonable approach.” – by Jason Harris

Disclosure: Dr. Markman reports no relevant financial disclosures.

Follow HemOncToday.com on Twitter.