HPV Testing: Greater Protection Against Cervical Cancer
The future of cervical abnormality detection, and thus the prevention of invasive cancers, lies in testing for human papillomavirus (HPV), rather than the more established cytology screening, according to the largest study to date. In fact, HPV screening appears to offer 60% to 70% greater protection against invasive cervical cancer than cytology.
The study results were published online November 2 in the Lancet.
A pooled analysis of 4 trials that involved more than 175,000 women 20 to 64 years of age found that the rate of detection of invasive cancers was similar with the 2 screening methods for the first 2.5 years of follow-up (rate ratio for HPV vs cytology, 0.79). However, detection was significantly lower in the HPV screening group thereafter (rate ratio, 0.45).
HPV screening was more effective in women 30 to 34 years of age than in older women. For all women, HPV screening done every 5 years offers better protection than cytology done every 3 years.
"Until now, there have been no direct estimates of the relative efficacy of HPV-based versus cytology-based screening for prevention of invasive cancer in women who undergo regular screening, of how variables like age affect this efficacy, and of the duration of protection," said lead author Guglielmo Ronco, MD, from the Centre for Cancer Prevention in Turin, Italy, in a statement. "Our analysis shows that HPV-based screening appears to prevent more invasive cervical cancers than does cytology, and on this basis, we recommend implementation of HPV-based cervical screening with triage from age 30 years at intervals of at least 5 years."
In an accompanying comment, Sandra D. Isidean, PhD, and Eduardo L. Franco, DrPH, both from McGill University in Montreal, point out that even though there are differences in the 4 randomized controlled trials, particularly with respect to management protocols triggered by test results, there was very little heterogeneity in terms of results; there was consistently lower overall detection of invasive cervical cancer in the groups screened for HPV.
"This finding seems to indicate that the effect of HPV-based screening on invasive cervical cancer incidence is much larger than any potential effect of differing management protocols from the trials," write Drs. Isidean and Franco.
"The future of cervical cancer screening in high-resource settings will most probably incorporate primary HPV testing, a science-driven change in strategy that particularly befits the post-HPV vaccination era," they note.
Over time, HPV screening might end up being less expensive while providing greater safety than conventional cervical cytology, they suggest. But to reap these benefits, "nations will need to consider important logistical challenges, including settling on the type of HPV screening test to be used, ascertaining appropriate screening ages and intervals, defining triage and management policies for HPV positive women, and ensuring quality of and adherence to revised policies," they conclude.
Studies Point to Efficacy
A number of studies have evaluated the effectiveness of HPV screening in various populations.
One study found HPV screening to be more effective in detecting high-grade lesions and preventing invasive cervical cancer than cytology in women 35 years and older (Lancet Oncol. 2010;11:249-257), as previously reported by Medscape Medical News.
HPV testing was also shown to be more effective than cytology or visual inspection of the cervix with acetic acid. It significantly reduced the incidence of advanced disease and related mortality in a study conducted in a low-resource setting (N Engl J Med. 2009;360:1385-1394).
The US Preventive Services Task Force recommends HPV screening in combination with Pap testing for women 30 to 65 years of age. This recommendation is in line with guidelines released by the by the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology.
Cumulative Incidence Lower
In their study, Dr. Ronco and colleagues conducted a follow-up that was a median of 6.5 years for 176,464 women 20 to 64 years of age. Women were randomly assigned to HPV-based screening or cytology-based screening (control group) in 4 studies: Swedescreen conducted in Sweden, POBASCAM conducted in the Netherlands, ARTISTIC conducted in England, and NTCC conducted in Italy.
Women in the control groups underwent either liquid-based (ARTISTIC) or conventional (all other studies) cytologic testing. At total of 107 invasive cervical carcinomas were identified.
For women with a negative cytology test on study entry, the cumulative incidence of invasive cervical cancer was 15.4 × 10⁵ after 3.5 years, and 36.0 × 10⁵ at 5.5 years. For those with a negative HPV test on study entry, the cumulative incidence was 4.6 × 10⁵ after 3.5 years and 8.7 × 10⁵ after 5.5 years.
The authors note that the cumulative incidence of cervical cancer was lower 5.5 years after a negative HPV result than 3.5 years after a negative cytology result, indicating that 5-year screening intervals for HPV testing are safer than 3-year intervals for cytology.
The proportion of adenocarcinomas decreased with age. In women younger than 30 years. It was 40% in women younger than 30 years, 35% in those 30 to 34 years, 30% in those 35 to 49 years, and 23% in those 50 years and older.
"Prevention of cancer in young women is a priority; our findings support HPV-based screening with triage at prolonged intervals, starting at age 30 years," conclude Dr. Ronco and colleagues.
The results of the study will be presented at EUROGIN 2013, which begins November 3 in Florence, Italy.
The study was supported by European Union, Belgian Foundation Against Cancer, KCE-Centre d'Expertise, IARC, the Netherlands Organisation for Health Research and Development, and the Italian Ministry of Health. Several of the study authors report financial relationships, as detailed in the paper. Dr. Isidean has have disclosed no relevant financial relationships. Dr. Franco reports serving as a consultant or advisory board member for companies involved in HPV vaccination (Merck, GlaxoSmithKline), HPV diagnostics (Roche, Qiagen, Gen-Probe), and cytology (Cytyc, Ikonisys). McGill University has received grants from Merck to support investigator-initiated research by Dr. Franco.