Front-line HPV DNA testing more sensitive than cytology in finding severe lesions for routine cervical cancer screening
Study in British Medical Journal first to demonstrate benefits of HPV DNA testing with Pap triage in a well-established organized screening program
Hilden, Germany - April 28, 2010 - Findings from a pilot demonstration in the Finnish population-based cervical cancer screening program demonstrate a higher sensitivity of Human Papillomavirus (HPV) DNA testing, followed by cytology (Pap test) triage, in detecting cervical disease and cancers compared to cytology alone. The 58,076 patient study, published in the British Medical Journal (BMJ) today, is the first to show the positive effects of incorporating HPV DNA frontline screening into a routine, formal registry-based cytology screening program that has been operating effectively for more than 50 years.
"This study demonstrated that implementing primary HPV DNA screening with cytology triage as the first choice can be considered", concluded lead study author Dr. Ahti Anttila, of the Finnish Cancer Registry. Results justify considering "gradual implementation of HPV screening also in other regions than involved in this trial," stated the study authors, who recommended that for women 35 years and older "primary HPV screening can be piloted in an organized program and that rollout towards a national implementation can be considered if the pilot will be favorable." The HPV screenings in the study were performed with QIAGEN's digene® HPV Test (also known as the digene® HC2 HPV DNA Test), which detects the high-risk types of HPV that can cause cervical cancer.
Many previous trials have consistently shown that HPV DNA testing with the digene® HPV Test is more sensitive than cytology for early detection and cervical cancer prevention, but no longitudinal studies had been undertaken to evaluate the value of primary HPV screening followed by cytology in a routine screening program. The Finnish data are the first results reported from a setting where the front-line HPV DNA test, followed by Pap triage, was integrated within a routine population-based screening programme. Finland has one of the oldest established cytology-based screening programs in Europe, low incidence and mortality rates for cervical cancer, and is considered a benchmark for a successful organized national program.
"This study clearly shows that even within a well organized cervical cancer screening program such as the one in Finland, the addition of the digene HPV Test results in earlier detection of cervical disease and fewer missed cases", said Peer Schatz, CEO of QIAGEN. "We hope the benefits realized in Finland will support the increased adoption and national rollout of HPV screening for women. QIAGEN has the most clinically-validated HPV DNA test portfolio for high-volume primary screening needs and is well prepared to meet the needs of governments and health ministries who are establishing or enhancing cervical cancer prevention programs."
Study design and results
In Finland women between 30 and 60 years are invited every five years to participate in the national cervical cancer screening program. This study tracked 58,076 women from Southern Finland who were invited for screening from January 2003 to December 2005. Women were randomized to receive either conventional cytology (Pap) screening alone, or to receive the digene HPV DNA Test, followed by cytology ("Pap triage") for those women with a positive HPV result. In the HPV testing arm, HPV negative results led to scheduling the next invitation after five years.
Outcomes of the study were obtained by linking the screening database to the population register and the cancer register. The collected data amounts to 191,218 woman-years at risk.
For both "invitees" (all women invited to the screening program) and "attendees" (women following the invitation and attending screening) more pre-cancerous and cancerous lesions (CIN 3, AIS or cervical cancers) were found in the HPV arm (invitees: 76 in the HPV group vs. 53 in the cytology group; attendees: 59 vs. 33). Although a higher number of cancer cases would have allowed a better evaluation of the performance, the study results clearly demonstrate a higher sensitivity of HPV testing in detecting CIN 3+: the relative risk of an HPV positive woman for developing CIN 3+ was two times higher than with positive cytology (RR 2.17; 95% CI: 1.38 to 3.51). Also high grade squamous intraepithelial lesions (HSIL), cervical cancers and adenocarcinoma in situ (AIS) were detected earlier in the HPV arm than in the cytology arm. Finally in women with negative cytology more cases of CIN 3+ were diagnosed compared to women being HPV negative (7 versus 2), so the risk of developing cervical cancer following a negative HPV test is lower (RR 0.28; 95% CI: 0.04 to 1.17).
About the digene HPV Test:
Worldwide, cervical cancer affects approximately 500,000 women annually and is the second-most-common malignancy found in women. HPV testing identifies women with high-risk HPV infections that can cause cervical cancer, enabling diagnosis and treatment to be put in place before cervical cancer develops. The digene HPV Test is approved in the U.S. for use together with a Pap test ("co-testing") in women 30 years and older, and as follow-up to inconclusive Pap test results ("ASCUS triage"). It is regarded as the "gold standard" in testing for high-risk types of HPV and is recommended in guidelines from leading U.S. medical organizations. In Europe, it is approved as an initial general population screening test either alone ("primary" or "frontline" screening) or together with a Pap test, as well as for ASCUS triage. The performance of the digene HPV Test has been published in more than 300 peer-reviewed journal articles and studied in clinical trials involving more than a million women worldwide. More than 40 million tests for carcinogenic HPV have been performed with the digene HPV Test. For more information, visit http://www.thehpvtest.com/.
QIAGEN N.V., a Netherlands holding company, is the leading global provider of sample and assay technologies. Sample technologies are used to isolate and process DNA, RNA and proteins from biological samples such as blood or tissue. Assay technologies are used to make such isolated bio-molecules visible. QIAGEN has developed and markets more than 500 sample and assay products as well as automated solutions for such consumables. The Company provides its products to molecular diagnostics laboratories, academic researchers, pharmaceutical and biotechnology companies, and applied testing customers for purposes such as forensics, animal or food testing and pharmaceutical process control. QIAGEN's assay technologies include one of the broadest panels of molecular diagnostic tests available worldwide. This panel includes the digene HPV Test, which is regarded as a "gold standard" in testing for high-risk types of human papillomavirus (HPV), the primary cause of cervical cancer, as well as a broad suite of solutions for infectious disease testing and companion diagnostics. QIAGEN employs more than 3,500 people in over 30 locations worldwide. Further information about QIAGEN can be found at http://www.qiagen.com/.