HPV16 variant lineage, clinical stage, and survival in women with invasive cervical cancer
1 Department of Pathology, University of Oklahoma Health Sciences Center, 940 SL Young Blvd, Oklahoma City, Oklahoma, 73104-5042, USA
2 Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Oklahoma Health Sciences Center, 800 NE 10th St. Suite 2001-2, Oklahoma City, Oklahoma, 73104-5418, USA
3 Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd, Room 5024, Rockville, Maryland 20852-7234, USA
4 Department of Obstetrics and Gynecology, University of Missouri Health System, 115 Business Loop 70W, Columbia, Missouri 56203-3244, USA
5 Department of Pathology and Laboratory Medicine, Tulane University Health Sciences, 1430 Tulane Avenue SL-79, New Orleans, Louisiana 70112-2699, USA
6 Obstetrics and Gynecology Department, Vanderbilt University Medical Center, 1161 21st Ave S, Nashville, Tennessee 37232-0011, USA
7 Department of Cancer Etiology, City of Hope and the Beckman Institute, 1500 East Duarte Rd, Duarte, CA 91010-3012, USA
Infectious Agents and Cancer 2011, 6:19 doi:10.1186/1750-9378-6-19Published: 28 October 2011
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.
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.
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.
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.