Age-specific evaluation of primary human papillomavirus screening vs conventional cytology in a randomized setting.
BACKGROUND
Human papillomavirus (HPV) DNA testing has shown higher sensitivity than cytology for detecting cervical lesions, but it is uncertain whether the higher sensitivity is dependent on the age of the woman being screened. We compared the age-specific performance of primary HPV DNA screening with that of conventional cytology screening in the setting of an organized population-based cervical cancer screening program in Finland.


METHODS
From January 1, 2003, to December 31, 2005, randomized invitations were sent to women aged 25-65 years for routine cervical cancer screening by primary high-risk HPV DNA testing (n = 54 207) with a Hybrid Capture 2 assay followed by cytology triage for women who were HPV DNA positive or by conventional cytology screening (n = 54 218). In both screening arms, cytology results of low-grade squamous intraepithelial lesion or worse triggered a referral for colposcopy. Relative rates (RRs) of detection to assess test sensitivity, specificity, and positive predictive values (PPVs) with 95% confidence intervals (CIs) were calculated for the histological endpoints of cervical intraepithelial neoplasia (CIN) grade 1 or higher (CIN 1+), CIN grade 2 or higher (CIN 2+), and CIN grade 3 or higher (CIN 3+). All statistical tests were two-sided.


RESULTS
The overall frequency of colposcopy referrals was 1.2% in both screening arms. Women younger than 35 years were referred more often in the HPV DNA screening vs the conventional screening arm (RR = 1.27, 95% CI = 1.01 to 1.60). The prevalence of histologically confirmed CIN or cancer was 0.59% in the HPV DNA screening arm vs 0.43% in the conventional screening arm. The relative rates of detection for CIN 1, CIN 2, and CIN 3+ for HPV DNA screening with cytology triage vs conventional screening were 1.44 (95% CI = 0.99 to 2.10), 1.39 (95% CI = 1.03 to 1.88), and 1.22 (95% CI = 0.78 to 1.92), respectively. The specificity of the HPV DNA test with cytology triage was equal to that of conventional screening for all age groups (99.2% vs 99.1% for CIN 2+, P = .13). Among women aged 35 years or older, the HPV DNA test with cytology triage tended to have higher specificity than conventional screening. The PPVs for HPV DNA screening with cytology triage were consistently higher than those for conventional screening. In both screening arms, the test specificities increased with increasing age of the women being screening, whereas the highest PPVs were observed among the youngest women being screened. Overall, 7.2% of women in the HPV DNA screening arm vs 6.6% of women in the conventional screening arm were recommended for intensified follow-up, and the percentages were highest among 25- to 29-year-olds (21.9% vs 10.0%, respectively).


CONCLUSIONS
Primary HPV DNA screening with cytology triage is more sensitive than conventional screening. Among women aged 35 years or older, primary HPV DNA screening with cytology triage is also more specific than conventional screening and decreases colposcopy referrals and follow-up tests.
Leinonen
Maarit
M
Mass Screening Registry, Finnish Cancer Registry, Pieni Roobertinkatu 9, FI-00130 Helsinki, Finland. maarit.leinonen@cancer.fi
Nieminen
Pekka
P
Kotaniemi-Talonen
Laura
L
Malila
Nea
N
Tarkkanen
Jussi
J
Laurila
Pekka
P
Anttila
Ahti
A
D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging; D052685:Alphapapillomavirus / Q000235:genetics / Q000302:isolation & purification*; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D003127:Colposcopy; D015986:Confounding Factors, Epidemiologic; D004279:DNA, Viral / Q000302:isolation & purification*; D055088:Early Detection of Cancer; D005260:Female; D005387:Finland; D006801:Humans; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D016017:Odds Ratio; D030361:Papillomavirus Infections / Q000150:complications / Q000175:diagnosis* / Q000821:virology; D011159:Population Surveillance; D011237:Predictive Value of Tests; D012017:Referral and Consultation; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D012680:Sensitivity and Specificity; D014218:Triage; D014412:Tumor Virus Infections / Q000150:complications / Q000175:diagnosis* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000517:prevention & control / Q000821:virology; D014626:Vaginal Smears / Q000379:methods; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000517:prevention & control / Q000821:virology
D004279:DNA, Viral