Final results of the POBASCAM trial reveal that for women aged 30+, the human papillomavirus (HPV) DNA test is the optimum cervical cancer screening option. The HPV DNA test prevents more cervical cancers than cytology alone, and detects lesions which cause cervical cancer earlier. Study results provide the strongest evidence to date in favor of using this test in national screening programs. The trial is published Online First in The Lancet Oncology.

In an associated comment, Hormuzd Katki and Nicolas Wentzensen from the National Cancer Institute, Bethesda, USA, explain:

“POBASCAM reinforces findings from cohort studies, clinical trials, and routine clinical practice by providing overwhelming evidence of the benefits of inclusion of HPV testing in screening programs.”

Although HPV testing is more precise than cytology at identifying precancerous high-grade cervical lesion, whether it provides greater protection in two screening round over 5 years has not been studied.

The trial, led by Chris Meijer and his team from the VU University Medical Center, Amsterdam, the Netherlands, examined almost 45,000 Dutch women aged between 29 to 56 years attending routine cervical screening.

The team examined the best age for starting HPV testing, and determined whether the test resulted in fewer high-grade cervical lesions and cervical cancer in the subsequent screening as a result of earlier detection and treatment of lesions.

Study participants were randomly assigned at the beginning of the investigation to receive either cytology alone, or HPV DNA testing as well as cytology. Five years later at the second screening, all women received HPV and cytology testing.

The researchers found that HPV testing in the first screen identified considerably more cancer precursors (cervical intraepithelial neoplasia grade 2 or worse [CIN2+]) compared with cytology alone.

At the second screening 5 years later, considerably fewer women in the HPV group had CIN grade 3 or worse (CIN3+) lesions and cervical cancer than women who received cytology alone at their first screening.

The researchers explain:

“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.”

In the HPV group, the enhanced protection against CIN3+ was primarily due to high-grade cervical lesions caused by HPV16 (one of the principal cancer-causing HPV types), being detected earlier. These results suggest that the test could eventually lower cancer-related morbidity and mortality.

The team discovered that the cumulative detection of CIN2+ and CIN3+ when both screenings were combined did not vary between women aged 29 to 33 years and those aged over 33, suggesting that the test did not result in over-diagnosis of regressive CIN2+ lesions in younger women.

The researchers say:

“Our results lend support to the implementation of HPV DNA testing in programmed cervical screening starting at age 30 years.”

Katki and Wentzensen add:

“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”

Written by Grace Rattue