An article published Online First and in the July edition of The Lancet Oncology reports that the combination of human papillomavirus (HPV) testing with regular liquid-based cytology (LBC) screening does not improve the detection of cervical cancer compared with LBC screening alone.
In the UK, liquid-based cytology (which is a liquid form of the Pap smear test) has replaced the conventional Pap smear test. It has been shown to improve detection of precancerous cervical cells called cervical intraepithelial neoplasia (CIN). Also it has reduced the number of unsatisfactory samples that require retesting. According to earlier research, testing for HPV in the cervix is more sensitive than conventional Pap smears and can detect CIN that smears can miss. However, it also results in more false positives than conventional smears.
In the UK, the present programme of cervical smear testing with LBC prevents about seventy percent of cancers. However it is unknown if supplementing HPV testing to routine cervical screening could raise the effectiveness of the screening programme in the UK.
Henry Kitchener and team conducted the ARTISTIC trial in order to investigate. Their work was the first randomised trial to measure combined LBC plus HPV testing with LBC alone in primary cervical screening. It included in total 24,510 women aged 20 to 64 years. All the participants attended general practice or family-planning clinics for routine cervical screening in Greater Manchester, UK. As part of the national screening programme they were also tested for HPV. The women were randomly assigned in a ratio of 3-1 to either have their HPV result revealed and acted upon or concealed from both the woman and the researcher. Women who were HPV positive with a negative smear in the revealed group underwent repeat testing at twelve months and a colposcopy was offered if they still tested positive. There were 18,386 women in the revealed group and 6,124 women in the concealed group.
There was monitoring and screening at three years for all the women in order to evaluate if as a result of the HPV testing, the revealed group had less pre-cancers because of superior detection and earlier treatment of underlying lesions.
Generally, the combination of testing with LBC and HPV did not detect more high-grade lesions than LBC testing alone. The results indicated that in the earlier screening round HPV testing did detect cases of CIN grade 3 or worse (CIN3+). Those cases were missed by LBC alone. But in the second round, there were fewer cases detected in the combined group. In addition, after examination of both screening rounds there was no considerable distinction between the two groups.
In the first series of screening there were 233 women (1.27 percent) in the revealed group that had CIN3+, compared with 80 women (1.31 percent) in the concealed group. In the second series of screening the number of women with CIN3+ lowered to 29 women (0.25 percent) in the revealed group and 18 women (0.47 percent) in the concealed group. In the combination of both rounds, there was no major statistical difference in the proportion of women found to have CIN3+ which were 1.5 percent in the revealed group and 1.77 percent in the concealed group.
The researchers explain that: “Over two rounds this trial showed no evidence that LBC combined with HPV testing in primary cervical screening detected more CIN2 or CIN3+ than cytology alone. This summed effect over two rounds is relevant because screening relies on repeated rounds to achieve its sensitivity.”
There will be a third round of screening six years after enrolment, as the ARTISTIC trial continues. The authors say this will: “Determine whether HPV testing could extend screening intervals because of the longer duration of protection conferred by a negative HPV result than with a negative LBC finding.”
“HPV testing in combination with liquid-based cytology in primary cervical screening (ARTISTIC): a randomised controlled trial”
Henry C Kitchener, Maribel Almonte, Claire Thomson, Paula Wheeler, Alexandra Sargent, Boyka Stoykova, Clare Gilham, Helene Baysson, Christopher Roberts, Robin Dowie, Mina Desai, Jean Mather, Andrew Bailey, Andrew Turner, Sue Moss, Julian Peto
DOI: 10.1016/S1470-2045(09)70156-1
Written by Stephanie Brunner (B.A)