Untypable human papillomavirus infection and risk of cervical intraepithelial neoplasia among women with abnormal cervical cytology

The risk of cervical intraepithelial neoplasia and/or invasive cervical cancer associated with untypable human papillomavirus (HPV) infections has been not investigated fully. HPV infection caused by 18 high-risk and 7 low-risk genotypes as detected by the INNO-LIPA genotyping system, was investigated in 4,258 women with abnormal Pap smear referred to a colposcopic service. The prevalence of HPV infection was 76.1%. Rates of cervical intraepithelial neoplasia grade 3+ were 0.88% (9/1,017) in HPV-negative subjects, 1.8% (7/380) in subjects with untypable HPV infection, 3.2% (11/343) in subjects with single/multiple low-risk types, 28.3% (201/709) in subjects with multiple low and high-risk types, 15.2% (162/1,069) in subjects with single high-risk types, and 31.2% (229/733) in those with multiple high-risk types. Compared to women without any HPV infection, the odds ratios of cervical intraepithelial neoplasia grade 2+ or grade 3+ in subjects with untypable or low-risk HPV genotypes were 5.73 (95% CI = 2.79-11.78) and 12.4 (95% CI = 6.31-24.5, P = 0.014 compared to untypable) and 3.1 (95% CI = 1.11-8.16) and 7.1 (95% CI = 2.9-17.2, P = 0.07 compared to untypable), respectively. In the subgroup of subjects with cervical intraepithelial neoplasia grade 1 or negative colposcopy/biopsy, the progression to cervical intraepithelial neoplasia grade 2+ at follow-up (median 25 months, range 6-70) was 2% (14/684), 3.4% (7/205), and 5.6% (11/195, P = 0.04 compared to negative) among negative, untypable, and low-risk HPV infection, respectively. The risk of cervical intraepithelial neoplasia associated with untypable HPV infection was higher than that recorded among uninfected women, but lower than the risk associated with low- or high-risk HPV genotypes.