5-type HPV mRNA versus 14-type HPV DNA test: test performance, over-diagnosis and overtreatment in triage of women with minor cervical lesions.
BACKGROUND
Repeat cytology and HPV testing is used in triage of women with minor cytological lesions. The objective of this study was to evaluate 14-type HPV DNA and 5-type HPV mRNA testing in delayed triage of women with ASC-US/LSIL.


METHODS
We compared a DNA test (Roche Cobas 4800) and an 5-type mRNA test (PreTect HPV-Proofer). In total 564 women were included in the study.


RESULTS
The sensitivity among solved cases for CIN3+ were 100 % (15/15) for both tests. The sensitivity for CIN2+ of the HPV DNA test was 100 % (38/38) relative to 79 % (30/38) for the 5-type HPV mRNA test. The corresponding estimates of specificity for CIN2+ among solved cases were 84 % (393/466; 95 % CI: 81-88) and 91 % (451/498; 95 % CI: 88-93). The positive predictive values for CIN3+ were 13.5 % (15/111) for DNA+ and 19.5 % (15/77) for 5-type mRNA+. Significantly more women screened with 5-type mRNA than DNA returned to screening (81 % vs 71 %, p < 0.01). Subsequently, significantly fewer women were referred for colposcopy/biopsies/treatment (19 % (105/564) vs 29 % (165/564), p < 0.01).


CONCLUSIONS
5-type HPV mRNA is more specific than 14-type HPV DNA in delayed triage of women with ASC-US/LSIL. The referral rate for colposcopy was 57 % higher for DNA+ relative to mRNA+ cases (165 vs 105), with the same detection rate of CIN3+, but the 5-type mRNA test had lower sensitivity for CIN2+. It is important to consider the trade-off between sensitivity and specificity of the diagnostic test when designing screening algorithms.
Department of Pathology, Ålesund Hospital, Møre and Romsdal Health Trust, Ålesund, Norway.
Bjørn
B
Westre
Department of Pathology, Ålesund Hospital, Møre and Romsdal Health Trust, Ålesund, Norway.
Anita
A
Giske
Department of Pathology, Ålesund Hospital, Møre and Romsdal Health Trust, Ålesund, Norway.
Hilde
H
Guttormsen
Department of Clinical Pathology, University Hospital of North Norway, 9038 Tromsø, Norway.
Sveinung Wergeland
SW
Sørbye
Research Group Epidemiology of Chronic Diseases, Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
Finn Egil
FE
Skjeldestad
CIN; CIN2; CIN3; Cervical cancer; DNA; HPV; Screening; Triage; mRNA