Efficacy of HPV DNA testing with cytology triage and/or repeat HPV DNA testing in primary cervical cancer screening.
BACKGROUND
Primary cervical screening with both human papillomavirus (HPV) DNA testing and cytological examination of cervical cells with a Pap test (cytology) has been evaluated in randomized clinical trials. Because the vast majority of women with positive cytology are also HPV DNA positive, screening strategies that use HPV DNA testing as the primary screening test may be more effective.


METHODS
We used the database from the intervention arm (n = 6,257 women) of a population-based randomized trial of double screening with cytology and HPV DNA testing to evaluate the efficacy of 11 possible cervical screening strategies that are based on HPV DNA testing alone, cytology alone, and HPV DNA testing combined with cytology among women aged 32-38 years. The main outcome measures were sensitivity for detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) within 6 months of enrollment or at colposcopy for women with a persistent type-specific HPV infection and the number of screening tests and positive predictive value (PPV) for each screening strategy. All statistical tests were two-sided.


RESULTS
Compared with screening by cytology alone, double testing with cytology and for type-specific HPV persistence resulted in a 35% (95% confidence interval [CI] = 15% to 60%) increase in sensitivity to detect CIN3+, without a statistically significant reduction in the PPV (relative PPV = 0.76, 95% CI = 0.52 to 1.10), but with more than twice as many screening tests needed. Several strategies that incorporated screening for high-risk HPV subtypes were explored, but they resulted in reduced PPV compared with cytology. Compared with cytology, primary screening with HPV DNA testing followed by cytological triage and repeat HPV DNA testing of HPV DNA-positive women with normal cytology increased the CIN3+ sensitivity by 30% (95% CI = 9% to 54%), maintained a high PPV (relative PPV = 0.87, 95% CI = 0.60 to 1.26), and resulted in a mere 12% increase in the number of screening tests (from 6,257 to 7,019 tests).


CONCLUSIONS
Primary HPV DNA-based screening with cytology triage and repeat HPV DNA testing of cytology-negative women appears to be the most feasible cervical screening strategy.
Naucler
Pontus
P
Department of Medical Microbiology, Lund University, Malmö University Hospital, Malmö, Sweden.
Ryd
Walter
W
Törnberg
Sven
S
Strand
Anders
A
Wadell
Göran
G
Elfgren
Kristina
K
Rådberg
Thomas
T
Strander
Björn
B
Forslund
Ola
O
Hansson
Bengt-Göran
BG
Hagmar
Björn
B
Johansson
Bo
B
Rylander
Eva
E
Dillner
Joakim
J
D000328:Adult; D000465:Algorithms; D001706:Biopsy; D003127:Colposcopy; D004279:DNA, Viral / Q000032:analysis*; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D008403:Mass Screening / Q000379:methods*; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000150:complications / Q000175:diagnosis*; D011237:Predictive Value of Tests; D016032:Randomized Controlled Trials as Topic; D012680:Sensitivity and Specificity; D013548:Sweden; D014218:Triage; D014412:Tumor Virus Infections / Q000150:complications / Q000175:diagnosis*; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000517:prevention & control* / Q000821:virology; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis / Q000517:prevention & control* / Q000821:virology
D004279:DNA, Viral