Quantitative human papillomavirus 16 and 18 levels in incident infections and cervical lesion development.
Human papillomavirus (HPV) RNA levels may be a more sensitive early indicator of predisposition to carcinogenesis than DNA levels. We evaluated whether levels of HPV-16 and HPV-18 DNA and messenger RNA (mRNA) in newly detected infections are associated with cervical lesion development. Female university students were recruited from 1990 to 2004. Cervical samples for HPV DNA, HPV mRNA, and Papanicolaou testing were collected tri-annually, and women were referred for colposcopically directed biopsy when indicated. Quantitative real-time polymerase chain reaction of L1 and E7 DNA and E7 mRNA was performed on samples from women with HPV-16 and HPV-18 infections that were incidently detected by consensus PCR. Adjusting for other HPV types, increasing E7 cervical HPV-16 mRNA levels at the time of incident HPV-16 DNA detection were associated with an increased risk of cervical intraepithelial neoplasia grade 2-3 (HR per 1 log(10) increase in mRNA = 6.36, 95% CI = 2.00-20.23). Increasing HPV-16 mRNA levels were also associated with an increased risk of cervical squamous intraepithelial lesions; the risk was highest at the incident positive visit and decreased over time. Neither HPV-16 E7 DNA levels nor HPV-18 E7 DNA nor mRNA levels were significantly associated with cervical lesion development. Report of >1 new partner in the past 8 months (relative to no new partners) was associated with increased HPV mRNA (viral level ratio [VLR] = 10.05, 95% CI = 1.09-92.56) and increased HPV DNA (VLR = 16.80, 95% CI = 1.46-193.01). In newly detected HPV-16 infections, increasing levels of E7 mRNA appear to be associated with an increased risk of developing cervical pre-cancer.
Winer
Rachel L
RL
Department of Epidemiology, University of Washington, Seattle, Washington, USA. rlw@u.washington.edu
Harris
Tiffany G
TG
Xi
Long Fu
LF
Jansen
Kathrin U
KU
Hughes
James P
JP
Feng
Qinghua
Q
Welebob
Carolee
C
Ho
Jesse
J
Lee
Shu-Kuang
SK
Carter
Joseph J
JJ
Galloway
Denise A
DA
Kiviat
Nancy B
NB
Koutsky
Laura A
LA
D000293:Adolescent; D000328:Adult; D002584:Cervix Uteri / Q000473:pathology / Q000821:virology; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D052161:Human papillomavirus 18 / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism; D065006:Papanicolaou Test; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000453:epidemiology* / Q000821:virology; D016133:Polymerase Chain Reaction / Q000379:methods; D011230:Precancerous Conditions / Q000453:epidemiology / Q000473:pathology / Q000821:virology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D014626:Vaginal Smears; D019562:Viral Load; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology / Q000473:pathology / Q000821:virology
D004279:DNA, Viral; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger; C059731:oncogene protein E7, Human papillomavirus type 16