Quantification of intracellular HPV E6/E7 mRNA expression increases the specificity and positive predictive value of cervical cancer screening compared to HPV DNA.
OBJECTIVE
Current methods for HPV screening rely on the detection of L1 DNA from high risk genotypes (HRHPV). These assays have very high negative predictive values (~99%), however, the specificity and positive predictive value of HPV DNA tests for pre-cancerous and cancerous lesions (CIN 2+) is less than 50%. The purpose of this study was to compare HPV DNA with intracellular HPV E6, E7 mRNA quantification in an effort to improve the performance of cervical cancer screening.


METHODS
Liquid-based cervical cytology specimens collected in either PreservCyt or SurePath were processed for routing cytology, HPV HRDNA detection by Hybrid Capture 2 and HPV E6, E7 mRNA quantification in cells using the same sample. We analyzed a total of 2049 samples including 73 with CIN 2, CIN 3, or squamous cell carcinoma by biopsy and 1694 samples from women with normal cytology.


RESULTS
The positive predictive value of HPV E6, E7 mRNA quantification in cells for CIN2+ was 78% which was greater than HPV DNA alone (43%). The specificity of HPV E6, E7 mRNA quantification was 96% based on normal cytology compared to 82% for HC2 while the specificity of HPV E6, E7 mRNA quantification based on CIN 2- histology was 85% compared to 35% for HC2.


CONCLUSIONS
With similar sensitivity and greater specificity/positive predictive value, HPV E6, E7 mRNA quantification in cells is an improvement over HPV DNA for cervical cancer screening.
Department of Pathology and Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, CA 94304, USA.
Gerald
G
Coquillard
Bibiana
B
Palao
Bruce K
BK
Patterson
D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000235:genetics*; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000473:pathology / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis / Q000473:pathology / Q000821:virology*
D004279:DNA, Viral; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger