HPV Test Beats Pap In Detecting Cervical Cancer
Science Daily — A new study led by McGill University researchers shows that the human papillomavirus (HPV) screening test is far more accurate than the traditional Pap test in detecting cervical cancer. The first round of the Canadian Cervical Cancer Screening Trial (CCCaST), led by Dr. Eduardo Franco, Director of the Division of Cancer Epidemiology at McGill's Faculty of Medicine, concluded that the HPV test's ability to accurately detect pre-cancerous lesions without generating false negatives was 94.6%, as opposed to 55.4% for the Pap test.
The results of the study, first-authored by Dr. Franco's former McGill PhD student Dr. Marie-Hélène Mayrand of the Centre hospitalier de l'Université de Montréal (CHUM), with colleagues from McGill, Université de Montréal, the Newfoundland and Labrador Public Health Laboratory and McMaster University, are published in the October 18 issue of The New England Journal of Medicine.
CCCaST is the first randomized controlled trial in North America of HPV testing as a stand-alone screening test for cervical cancer. The first round followed 10,154 women aged 30 to 69 in Montreal, Quebec and St. John's, Newfoundland who were enrolled in the study from 2002 to 2005. The study was funded by a grant from the Canadian Institutes of Health Research (CIHR).
The study concluded that while the HPV test's sensitivity was nearly 40% greater than the Pap test's, the Pap did, however, slightly edge out HPV for accuracy on the specificity scale -- its ability to accurately detect pre-cancerous lesions without generating false positives -- at 96.8% versus 94.1%.
"We already knew before conducting this study that the sensitivity of Pap left a lot to be desired," said Dr. Franco, James McGill Professor in the Departments of Oncology and Epidemiology and Biostatistics, and Director of the Division of Cancer Epidemiology at McGill University's Faculty of Medicine. "However, 55.4% accuracy is only slightly above chance. Flipping a coin gives you 50%."
The Papanicolaou (or Pap) test was invented by Dr. Georgios N. Papanicolaou in the 1940s and requires technicians to look under a microscope for abnormalities in cell samples collected from the patient's cervix. It has been the standard screening procedure for cervical cancer for almost 50 years. The HPV test also requires the collection of cervical samples, but the analysis process is automated and detects the DNA of high-risk human papillomavirus (HPV) strains known to cause cervical cancer.
A screening test's sensitivity is usually considered a more premium parameter than specificity, according to Dr. Franco. "A false positive may be very disturbing and psychologically distressing for the patient, but in the end, she's free of disease. False negatives are very serious business, however. The patient will be assured that she's negative, all the while a pre-cancer has a chance to become a cancer or her existing cancer has a chance to grow."
Though the results of the CCCaST study might have a bearing on the ongoing debate about vaccinating young women against HPV, Dr. Franco stressed that the two issues should be considered separately. "Vaccination is primary prevention; this study is about secondary prevention, which refers to screening. Even women who take the vaccine will still need to be screened, because the vaccines that are available now only prevent about 70% of all cervical cancers, and they're primarily for young women. The HPV test may be ideal for vaccinated women once they reach screening age, because it gives us an opportunity to monitor the protection that the vaccine is supposed to give them."
Dr. Franco added that, while the HPV screening test is now more expensive than a Pap test, that will likely change over time. "Moreover, because of its higher sensitivity and only slightly lower specificity, patients would only require an HPV test once every three years instead of annually, as is necessary with the Pap test."
Note: This story has been adapted from material provided by McGill University.
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NEJM abstracts
Human Papillomavirus DNA versus Papanicolaou Screening Tests for Cervical Cancer
Marie-Hélène Mayrand, M.D., Eliane Duarte-Franco, M.D., Isabel Rodrigues, M.D., Stephen D. Walter, Ph.D., James Hanley, Ph.D., Alex Ferenczy, M.D., Sam Ratnam, Ph.D., François Coutlée, M.D., Eduardo L. Franco, Dr.P.H., for the Canadian Cervical Cancer Screening Trial Study Group
ABSTRACT
Background To determine whether testing for DNA of oncogenic human papillomaviruses (HPV) is superior to the Papanicolaou (Pap) test for cervical-cancer screening, we conducted a randomized trial comparing the two methods.
Methods We compared HPV testing, using an assay approved by the Food and Drug Administration, with conventional Pap testing as a screening method to identify high-grade cervical intraepithelial neoplasia in women ages 30 to 69 years in Montreal and St. John's, Canada. Women with abnormal Pap test results or a positive HPV test (at least 1 pg of high-risk HPV DNA per milliliter) underwent colposcopy and biopsy, as did a random sample of women with negative tests. Sensitivity and specificity estimates were corrected for verification bias.
Results A total of 10,154 women were randomly assigned to testing. Both tests were performed on all women in a randomly assigned sequence at the same session. The sensitivity of HPV testing for cervical intraepithelial neoplasia of grade 2 or 3 was 94.6% (95% confidence interval [CI], 84.2 to 100), whereas the sensitivity of Pap testing was 55.4% (95% CI, 33.6 to 77.2; P=0.01). The specificity was 94.1% (95% CI, 93.4 to 94.8) for HPV testing and 96.8% (95% CI, 96.3 to 97.3; P<0.001) for Pap testing. Performance was unaffected by the sequence of the tests. The sensitivity of both tests used together was 100%, and the specificity was 92.5%. Triage procedures for Pap or HPV testing resulted in fewer referrals for colposcopy than did either test alone but were less sensitive. No adverse events were reported.
Conclusions As compared with Pap testing, HPV testing has greater sensitivity for the detection of cervical intraepithelial neoplasia. (Current Controlled Trials number, ISRCTN57612064 [controlled-trials.com] .)
Source Information
From the Departments of Oncology and Epidemiology & Biostatistics (M.-H.M., J.H., F.C., E.L.F.), Family Medicine (E.D.-F.), and Pathology (A.F.), McGill University, Montreal; the Départements d'Obstétrique-Gynécologie (M.-H.M.) and de Médecine Familiale (I.R.), Université de Montréal, Montreal; the Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON (S.D.W.); the Sir Mortimer B. Davis–Jewish General Hospital, Montreal (A.F.); the Newfoundland Public Health Laboratory, St. John's (S.R.); and the Département de Microbiologie–Infectiologie, Hôpital Notre-Dame du Centre Hospitalier de l'Université de Montréal, Montreal (F.C.) — all in Canada.
Address reprint requests to Dr. Franco at the Division of Cancer Epidemiology, McGill University, 546 Pine Ave. W., Montreal, QC H2W 1S6, Canada, or at eduardo.franco@mcgill.ca.
content.nejm.org
Human Papillomavirus and Papanicolaou Tests to Screen for Cervical Cancer
Pontus Naucler, M.D., Ph.D., Walter Ryd, M.D., Sven Törnberg, M.D., Ph.D., Anders Strand, M.D., Ph.D., Göran Wadell, M.D., Ph.D., Kristina Elfgren, M.D., Ph.D., Thomas Rådberg, M.D., Björn Strander, M.D., Ola Forslund, Ph.D., Bengt-Göran Hansson, Ph.D., Eva Rylander, M.D., Ph.D., and Joakim Dillner, M.D., Ph.D.
ABSTRACT
Background Screening for cervical cancer based on testing for human papillomavirus (HPV) increases the sensitivity of detection of high-grade (grade 2 or 3) cervical intraepithelial neoplasia, but whether this gain represents overdiagnosis or protection against future high-grade cervical epithelial neoplasia or cervical cancer is unknown.
Methods In a population-based screening program in Sweden, 12,527 women 32 to 38 years of age were randomly assigned at a 1:1 ratio to have an HPV test plus a Papanicolaou (Pap) test (intervention group) or a Pap test alone (control group). Women with a positive HPV test and a normal Pap test result were offered a second HPV test at least 1 year later, and those who were found to be persistently infected with the same high-risk type of HPV were then offered colposcopy with cervical biopsy. A similar number of double-blinded Pap smears and colposcopies with biopsy were performed in randomly selected women in the control group. Comprehensive registry data were used to follow the women for a mean of 4.1 years. The relative rates of grade 2 or 3 cervical intraepithelial neoplasia or cancer detected at enrollment and at subsequent screening examinations were calculated.
Results At enrollment, the proportion of women in the intervention group who were found to have lesions of grade 2 or 3 cervical intraepithelial neoplasia or cancer was 51% greater (95% confidence interval [CI], 13 to 102) than the proportion of women in the control group who were found to have such lesions. At subsequent screening examinations, the proportion of women in the intervention group who were found to have grade 2 or 3 lesions or cancer was 42% less (95% CI, 4 to 64) and the proportion with grade 3 lesions or cancer was 47% less (95% CI, 2 to 71) than the proportions of control women who were found to have such lesions. Women with persistent HPV infection remained at high risk for grade 2 or 3 lesions or cancer after referral for colposcopy.
Conclusions The addition of an HPV test to the Pap test to screen women in their mid-30s for cervical cancer reduces the incidence of grade 2 or 3 cervical intraepithelial neoplasia or cancer detected by subsequent screening examinations. (ClinicalTrials.gov number, NCT00479375 [ClinicalTrials.gov] .)
Source Information
From the Department of Medical Microbiology, Malmö University Hospital, Lund University (P.N., O.F., B.-G.H., J.D.); the Department of Pathology and Clinical Cytology (W.R.), the Department of Obstetrics and Gynecology (T.R., B.S.), and the Oncology Center (B.S.), Sahlgrenska University Hospital, Gothenburg; the Cancer Screening Unit, Oncology Center (S.T.) and the Department of Obstetrics and Gynecology (K.E.), Karolinska University Hospital, and the Division of Gynecology, Danderyd Hospital (E.R.), Karolinska Institutet, Stockholm; the Department of Medicine, Dermatology, and Venereology, University Hospital, Uppsala (A.S.); and the Department of Virology, University of Northern Sweden, Umeå (G.W.) — all in Sweden.
Address reprint requests to Dr. Dillner at the Department of Medical Microbiology, Lund University, Malmö University Hospital, Malmö S-20502, Sweden.
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