- Does HPV testing outperform the Pap test as a screen for cervical cancer?
Andrew M. Kaunitz, MD (Examining the Evidence; December 2007)
The final results of the Population-Based Screening Study Amsterdam (POBASCAM), published online in The Lancet Oncology, provide the strongest evidence to date in support of HPV testing as a cervical cancer screening strategy, according to Rijkaart and colleagues, authors of the study.1
The POBASCAM trial involved nearly 45,000 women 29 to 56 years old who attended routine cervical screening in the Netherlands. Investigators examined whether HPV testing was associated with fewer high-grade cervical lesions and cervical cancer in the second round of screening because of earlier detection and treatment of lesions. They also sought to determine the most appropriate age to initiate HPV testing.
At the start of the study, women were randomly assigned to cotesting with HPV DNA and Pap testing or to cytology alone. At the second screening round 5 years later, HPV and cytology testing were performed on all women.
In the first screen, the arm that included HPV testing identified significantly more cancer precursors (cervical intraepithelial neoplasia [CIN] grade 2 or worse) than cytology alone. Five years later, significantly fewer women had CIN 3 or worse and cervical cancer in the HPV group than in the group that underwent cytology alone (88 of 19,579 women in the HPV group vs 122 of 19,731 women in the control group [relative risk, 0.73; 95% confidence interval (CI), 0.55–0.96; P=.023]). Cervical cancer was also less common in the HPV group than in the control group (4 of 19,579 women in the HPV group vs 14 of 19,731 women in the control group [relative risk, 0.29; 95% CI, 0.10–0.87; P=.031]).
“Implementation of HPV DNA testing in cervical screening leads to earlier detection of clinically relevant CIN grade 2 or worse, which, when adequately treated, improves protection against CIN grade 3 or worse and cervical cancer,” the investigators concluded.
Improved protection against CIN 3 and worse in the HPV group was largely due to early detection of high-grade cervical lesions caused by HPV 16, which, along with HPV 18, is responsible for more than 70% of cervical cancers. This finding indicates that HPV testing could, eventually, lead to a reduction in the rate of cancer-related illness and death.
When data from both screening rounds were combined, the cumulative detection of CIN 2+ and CIN 3+ did not differ between women 29 to 33 years old and women older than 33 years, indicating that HPV testing did not lead to overdiagnosis of regressive CIN 2+ lesions in younger women.
“Our results…lend support to the implementation of HPV DNA testing in programmed cervical screening starting at age 30 years,” the investigators write.
The authors of an accompanying commentary observe that the “POBASCAM trial shows that 5-year screening intervals are safe, and that conservative management of HPV-positive women can control excess CIN grade 2 or 3 while preventing cervical cancer. However, how the POBASCAM protocol would perform in other populations that have different baseline cancer rates, compliance, and management infrastructure, is unclear.”2