HPV16 variant lineage, clinical stage, and survival in women with invasive cervical cancer.
BACKGROUND
HPV16 variants are associated with different risks for development of CIN3 and invasive cancer, although all are carcinogenic. The relationship of HPV 16 variants to cancer survival has not been studied.


METHODS
155 HPV16-positive cervical cancers were categorized according to European and non-European variant patterns by DNA sequencing of the E6 open reading frame. Clinico-pathologic parameters and clinical outcome were collected by chart review and death registry data.


RESULTS
Of the 155 women (mean age 44.7 years; median follow-up 26.7 months), 85.2% harbored European variants while 14.8% had non-European sequences. HPV16 variants differed by histologic cell type (p = 0.03) and stage (1 vs. 2+; p = 0.03). Overall, 107 women (68.0%) were alive with no evidence of cancer, 42 (27.1%) died from cervical cancer, 2 (1.3%) were alive with cervical cancer, and 4 (2.6%) died of other causes. Death due to cervical cancer was associated with European variant status (p < 0.01). While 31% of women harboring tumors with European variants died from cervical cancer during follow-up, only 1 of 23 (4.4%) non-European cases died of cancer. The better survival for non-European cases was partly mediated by lower stage at diagnosis.


CONCLUSIONS
Overall, invasive cervical cancers with non-European variants showed a less aggressive behavior than those with European variants. These findings should be replicated in a population with more non-European cases.
Department of Pathology, University of Oklahoma Health Sciences Center, 940 SL Young Blvd, Oklahoma City, Oklahoma, 73104-5042, USA. rosemary-zuna@ouhsc.edu.
Rosemary E
RE
Zuna
Erin
E
Tuller
Nicolas
N
Wentzensen
Cara
C
Mathews
Richard A
RA
Allen
Rebecca
R
Shanesmith
S Terence
ST
Dunn
Michael A
MA
Gold
Sophia S
SS
Wang
Joan
J
Walker
Mark
M
Schiffman