Molecular variants of human papillomavirus types 16 and 18 preferentially associated with cervical neoplasia

Abstract

In order to determine geographically related intratypic variation in human papillomavirus (HPV) type 16 and 18 isolates that could be associated with lesion development, data were analysed from an ongoing cohort study of the natural course of infection of HPVs and cervical neoplasia. Testing for HPVs was carried out by PCR and molecular variants of these HPVs were characterized by sequence analysis of the long control region and by dot blot hybridization of the E6 and L1 genes. Tests for HPV were done in multiple first-year specimens from 1690 women enrolled in a cancer screening program from 1993 to 1997. Subjects were followed-up by cytology and cervicography for detection of cervical lesions. Seven variants of HPV-16 and four of HPV-18 were detected in one or more specimens from 65 subjects. The same variant was found in specimens taken on different visits from each case of persistent infection. Overall, non-European variants tended to persist more frequently [odds ratio (OR) l 4n5 ; 95 % confidence interval (CI), 1n6-12n4] than European (E) variants (OR l 2n5 ; 95 % CI, 1n3-4n9), relative to the risk of persistence for nononcogenic HPVs. In addition, non-E variants were more strongly associated with risk of both prevalent (age-and race-adjusted OR l 172n2 ; 95 % CI, 47n1-630n1) and incident [relative risk (RR) l 22n5 ; 95 % CI, 6n0-83n9] high-grade lesions than E variants (prevalent lesions OR l 46n3; 95 % CI, 15n5-138n0 and incident lesons RR l 6n1 ; 95 % CI, 1n3-27n4), relative to the risk for HPVnegative women. Although consistent, the latter differences were not statistically significant. If confirmed in other populations, measurement of intratypic variation of HPV-16 and -18 has the potential to serve as an ancillary tool in cervical cancer screening.

Variants of the long control region and the E6 oncogene in European human papillomavirus type 16 isolates: implications for cervical disease

“…A statistically significant association was observed between non-European LCR variants containing this polymorphism and disease status in a study of women from Costa Rica (Hildesheim et al, 2001). Similar results were obtained in a Brazilian and in a north American study (Xi et al, 1997;Villa et al, 2000). Moreover, we could show that in Italian women, the Asian-American variant had a nine-fold higher prevalence in cervical cancer than in low-grade precursor lesions (Zehbe et al, 2001b ) and in the Finnish group the one case infected with this variant progressed (Kurvinen et al, 2000).…”

Human Papillomavirus Type 16 Variant Analysis of E6, E7, and L1 Genes and Long Control Region in Identification of Cervical Carcinomas in Patients in Northeast China

“…HPV 16 variants, which vary by Յ2% from HPV 16 prototype nucleotide sequences, have been identified as the following six phylogenetic branches: European (E), Asian (As), Asian-American (AA), African-1 (Af-1), African-2 (Af-2), and northern American (NA) variants (18,52). Several researchers had reported correlations between specific HPV 16 variants and persistent viral infection, followed by the development of malignant lesions (3,4,16,37,43,49,50). Non-European variants were found to be associated with an excess risk of cervical cancer (37).…”

Association of human papillomavirus type 31 variants with risk of cervical intraepithelial neoplasia grades 2–3

“…Studies of the intratypic variation, i.e., the variant, a level below the taxon of type, have focused mainly on HPV16 and HPV18, showing that some variants were more aggressive than others. [6][7][8][9][10][11][12] HPV31 is one of the oncogenic types, most closely related to HPV16. Prevalence of some HPV types may vary geographically.…”