HPV Testing May Detect More Precancerous Cells Than Conventional Cytology

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As part of a well-established organized screening program, primary human papillomavirus (HPV) screening with cytology triage is more sensitive than conventional cytology in the detection of cervical intraepithelial neoplasia (CIN) grade III, according to the results of a randomized trial reported online April 28 in the BMJ.

"The incidence of invasive cancer is the most informative standard in the evaluation of cervical cancer screening programmes and screening methods," write Ahti Anttila, PhD, research director, Mass Screening Registry of the Finnish Cancer Registry in Helsinki, Finland, and colleagues. "We evaluated the impact of primary HPV DNA screening with cytology triage on cervical cancer, severe ...CIN, or adenocarcinoma in situ (as a composite outcome referred to as CIN III+)."

In southern Finland from 2003 to 2005, a total of 58,076 women (aged 30 - 60 years) were invited to take part in the routine population-based screening program for cervical cancer. Participants were randomly selected to undergo a primary HPV DNA test (hybrid capture II) with cytology triage if the result was positive, or to conventional cytologic screening. The primary study endpoint was CIN III+ occurring from 2003 to 2007, as determined from record linkage between files from the screening registry and the national cancer registry.

Total follow-up was 95,600 woman-years in the HPV group and 95,700 woman-years of follow-up in the conventional group. During follow-up, there were 76 and 53 cases of CIN III+, respectively, including 6 and 8 cervical cancers, respectively. For the HPV group vs the conventional group, the relative rate (RR) of CIN III+ was 1.44 (95% confidence interval [CI], 1.01 - 2.05) for all women invited for screening and 1.77 (95% CI, 1.16 - 2.74) for women who participated in the screening.

The RR of subsequent CIN III+ was 0.28 (95% CI, 0.04 - 1.17) among women with a normal or negative test result, and the rate of cervical cancer between groups was 0.75 (95% CI, 0.25 - 2.16) among women invited for screening and 1.98 (95% CI, 0.52 - 9.38) among those who took part in the screening.

"When incorporated into a well established organised screening programme, primary HPV screening with cytology triage was more sensitive than conventional cytology in detecting CIN III+ lesions," the study authors write. "The number of cases of cervical cancer was small, but considering the high probability of progression of CIN III the findings are of importance regarding cancer prevention."

Limitations of this study include relatively low screening attendance rate, potential fluctuations in diagnostic criteria during the study period, and limited statistical power to analyze any impact on invasive cervical cancer.

"Primary HPV screening should be piloted in an organised programme, and extension towards a national implementation should be considered if the outcome is favourable," the study authors conclude. "As characteristics and organisational details between cervical cancer screening programmes are highly variable in different countries, each programme needs to evaluate the new methods in their own context.... We think that gradual implementation of HPV screening in regions other than those in this trial is justified."

The European Commission, Europe Against Cancer action programme through European Cervical Cancer Screening Network; the Academy of Finland; and the Cancer Organisation of Finland supported this study. The study authors have disclosed no relevant financial relationships.

BMJ. Published online April 28, 2010.


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