HPV16 variant lineage, clinical stage, and survival in women with invasive cervical cancer

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.While the association of HPV genotypes and cervical carcinoma is well established, the reasons that only a subset of lesions associated with high-risk genotypes progress to invasive cancer remain elusive. Influential variables likely include individual host factors, viral differences or combinations of both.One variable that could contribute to differences in biological behavior of HPV- associated lesions is that of HPV DNA sequence variation. HPV16, which is the most prevalent HPV genotype and is associated with approximately half of cervical cancers worldwide [1], has well-documented DNA sequence variants. HPV variants are defined as isolates with primary DNA sequence differences that total no more than 2% of the L1 open reading frame (ORF) of the prototype sequen