HPV16 E6 oncogene variants in women with cervical intraepithelial neoplasia

Human papillomaviruses (HPVs) are strongly associated with the development of high grade cervical intraepithelial neoplasia (CIN) and cervical carcino ma, with between 40-80% of patients with cervical carcinoma being attribute d to a single HPV type, HPV16 depending on the methods used and geographica l location of the particular study [van den Brule et al., 1996]. An HPV16 E 6 variant has been described which is strongly associated with high grade C IN [Ellis et al., 1997] and with the human leukocyte antigen (HLA)-B7 genot ype in women with cervical carcinoma where HLA-B7 positive patients were de monstrated to have a significantly poorer clinical outcome [Ellis et at., 1 995]. To determine whether this HPV16 E6 variant might play a significant r ole in the pathogenesis of cervical disease, 174 HPV16 positive women were selected from those attending the colposcopy clinics of Guy's and St Thomas ' Hospital Trust following polymerase chain reaction (PCR) amplification of HPV16 L1 or E5 DNAs from cervical brush swabs or fixed biopsy tissue. HPV1 6 E6 DNA was amplified by PCR and the variant sequence was identified by Ms p 1 restriction enzyme digestion, as the nucleotide substitution creates an additional unique Msp 1 site. The study group comprised 29 normal controls , 7 women with borderline cytology, 123 women with cervical dysplasia and 1 2 women with cervical cancer. 101/174 (58%) of these women had amplifiable E6 DNA and restriction enzyme digestion was performed on 95 of these. The v ariant E6 sequence was identified in 3/95 (3%) individuals, two of whom had normal histology and one had a CIN II lesion. Wild type E6 sequence was id entified in the remaining 92/95 (97%) individuals. These data suggest that this particular E6 variant does not play a major role in the pathogenesis o f HPV16 related cervical disease in women living in the South London area. J. Med. Virol. 60:337-341, 2000. (C) 2000 Wiley-Liss, Inc.