Human papillomavirus mRNA and p16 detection as biomarkers for the improved diagnosis of cervical neoplasia.
Human papillomavirus (HPV) infection of the genital tract is very common and normally follows a benign clinical course; however, in an unfortunate minority of infected individuals, it can cause disease that sometimes leads to cancer. It is accepted that HPV DNA testing has a role in the management of cervical disease both in a prevaccination and postvaccination era; however, to improve the specificity of this approach, there is a requirement to develop and validate tools/assays that can identify women at risk for progressive disease. There is evidence to suggest that detection of viral gene expression both directly and indirectly may constitute a more specific approach for delineating clinically significant infection compared with HPV DNA-based assays. HPV oncogene expression and evidence of its deregulation can be monitored through direct detection of viral mRNA transcripts or through detection of the cellular protein p16. For both approaches, commercial assays have been introduced and numerous studies have been conducted. The present article describes the scientific theory underpinning these approaches, their amenability to routine-diagnostic specimens/settings, and the clinical data that has been garnered through their application thus far. Currently, there is promising data indicating that HPV mRNA and p16 might play an important role in future cervical cancer screening scenarios. Still, large randomized studies are necessary to confirm the preliminary data.


METHODS
PubMed and OVID were interrogated with search terms "HPV RNA;" "HPV mRNA;" "HPV transcript-detection, testing, and methods;" "p16" AND "cervical cancer;" "p16" AND "CIN;" "p16" AND "histology"; "p16" AND "cytology;" "p16;" and "screening."
Cuschieri
Kate
K
Specialist Virology Centre, Royal Infirmary of Edinburgh, United Kingdom. Kate.Cuschieri@luht.scot.nhs.uk
Wentzensen
Nicolas
N
D014408:Biomarkers, Tumor / Q000032:analysis*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005260:Female; D006801:Humans; D008403:Mass Screening / Q000379:methods; D009363:Neoplasm Proteins / Q000235:genetics*; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000235:genetics; D011230:Precancerous Conditions / Q000175:diagnosis / Q000235:genetics / Q000821:virology; D012333:RNA, Messenger / Q000032:analysis*; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000821:virology
D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D012333:RNA, Messenger