Human papillomavirus testing for the detection of high-grade cervical intraepithelial neoplasia and cancer: final results of the POBASCAM randomised controlled trial
Mené auprès de 44 938 femmes (22 420 cas et 22 518 témoins) âgées de 29 à 56 ans et participant à un programme néerlandais de dépistage du cancer du col de l'utérus, cet essai randomisé évalue l'intérêt d'un test de recherche de l'ADN du papillomavirus humain pour la détection précoce de néoplasies intraépithéliales ou de cancers du col de l'utérus
Human papillomavirus (HPV) testing is more sensitive for the detection of high-grade cervical lesions than is cytology, but detection of HPV by DNA screening in two screening rounds 5 years apart has not been assessed. The aim of this study was to assess whether HPV DNA testing in the first screen decreases detection of cervical intraepithelial neoplasia (CIN) grade 3 or worse, CIN grade 2 or worse, and cervical cancer in the second screening. In this randomised trial, women aged 29?56 years participating in the cervical screening programme in the Netherlands were randomly assigned to receive HPV DNA (GP5+/6+-PCR method) and cytology co-testing or cytology testing alone, from January, 1999, to September, 2002. Randomisation (in a 1:1 ratio) was done with computer-generated random numbers after the cervical specimen had been taken. At the second screening 5 years later, HPV DNA and cytology co-testing was done in both groups; researchers were masked to the patient's assignment. The primary endpoint was the number of CIN grade 3 or worse detected. Analysis was done by intention to screen. The trial is now finished and is registered, number ISRCTN20781131. 22?420 women were randomly assigned to the intervention group and 22?518 to the control group; 19?999 in the intervention group and 20?106 in the control group were eligible for analysis at the first screen. At the second screen, 19?579 women in the intervention group and 19?731 in the control group were eligible, of whom 16?750 and 16?743, respectively, attended the second screen. In the second round, CIN grade 3 or worse was less common in the intervention group than in the control group (88 of 19?579 in the intervention groupvs122 of 19?731 in the control group; relative risk 0·73, 95% CI 0·55?0·96; p=0·023). Cervical cancer was also less common in the intervention group than in the control group (four of 19?579 in the intervention groupvs14 of 19?731; 0·29, 0·10?0·87; p=0·031). In the baseline round, detection of CIN grade 3 or worse did not differ significantly between groups (171 of 19?999vs150 of 20?106; 1·15, 0·92?1·43; p=0·239) but was significantly more common in women with normal cytology (34 of 19?286vs12 of 19?373; 2·85, 1·47?5·49; p=0·001). Furthermore, significantly more cases of CIN grade 2 or worse were detected in the intervention group than in the control group (267 of 19?999vs215 of 20?106; 1·25, 1·05?1·50; p=0·015). In the second screen, fewer HPV16-positive CIN grade 3 or worse were detected in the intervention group than in the control group (17 of 9481vs35 of 9354; 0·48, 0·27?0·85; p=0·012); detection of non-HPV16-positive CIN grade 3 or worse did not differ between groups (25 of 9481vs25 of 9354; 0·99, 0·57?1·72; p=1·00). The cumulative detection of CIN grade 3 or worse and CIN grade 2 or worse did not differ significantly between study arms, neither for the whole study group (CIN grade 3 or worse: 259 of 19?999vs272 of 20?106; 0·96, 0·81?1·14, p=0·631; CIN grade 2 or worse: 427 of 19?999vs399 of 20?106; 1·08, 0·94?1·24; p=0·292), nor for subgroups of women invited for the first time (CIN grade 3 or worse in women aged 29?33 years: 102 of 3139vs105 of 3128; 0·97, 0·74?1·27; CIN grade 2 or worse in women aged 29?33 years: 153 of 3139vs151 of 3128; 1·01, 0·81?1·26; CIN grade 3 or worse in women aged 34?56 years: 157 of 16?860vs167 of 16?978; 0·95, 0·76?1·18; CIN grade 2 or worse in women aged 34?56 years: 274 of 16?860vs248 of 16?978; 1·11, 0·94?1·32). 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. Early detection of high-grade cervical legions caused by HPV16 was a major component of this benefit. Our results lend support to the use of HPV DNA testing for all women aged 29 years and older. Zorg Onderzoek Nederland (Netherlands Organisation for Health Research and Development).
The Lancet Oncology , résumé, 2010