Human papillomavirus type 16 variant analysis of E6, E7, and L1 [corrected] genes and long control region in [corrected] cervical carcinomas in patients in northeast China

Abstract

Human papillomavirus type 16 (HPV 16) plays a cardinal role in the pathogenesis of cervical cancer. HPV 16 has intratypic variants which show different geographical distributions and different oncogenic potentials. To analyze the presence of sequence variations of HPV 16 variants in northeast China, 71 cervical carcinomas were identified by HPV typing. HPV 16-positive specimens were analyzed by PCR-directed sequencing in the E6, E7, and L1 genes and the LCR (long control region). The variation data were compared with those of neighboring districts. In this hospital-based study, HPV 16 was the most common type (73.24%). In HPV 16-positive specimens, 67.31% belonged to the European (E) lineage, while 32.69% were Asian (As) variants. The Asian-American (AA), African-1 (Af-1), African-2 (Af-2), and northern American (NA) lineages were not detected. The most frequently observed variation sites were T178G (32.69%) in E6; A647G (34.62%), G666A (38.46%), and T846C (32.69%) in E7; C6826T (36.17%) and G7060A (61.70%) in L1; and G7521A (98.08%) in the LCR. The most prevalent amino acid variations were D25E in E6 and N29S in E7. In addition, 28 novel variations of HPV 16 were reported. Some covariations between different genes were obtained. In this study, HPV 16 variants belonged to the European lineage and the Asian lineage. Compared with neighboring districts, the distribution of HPV 16 variants in northeast China had a typical pattern. As the first report on HPV 16 variants in northeast China, it should be helpful for designing a HPV vaccine and HPV vaccination program in China.

Fig. 1

A sequencing electropherogram showed frequently detected nucleotide variations in different genomic segments of HPV 16. (a) E6 T178A; (b) E7 G666A; (c) L1 G7060A; (d) LCR G7521A. (Top) Prototype sequences indicated by arrows; (bottom) variant sequences indicated by arrows.

Fig. 2

Nucleotide sequence variations among the HPV 16 isolates. The E6, E7, L1, and LCR variants were identified in 52 samples from northeast China. The nucleotide positions of detected mutations are written vertically across the top and are indicated by the corresponding nucleotide letter. The absence of variations relative to the prototype is represented by dashes. The identification codes of the samples are indicated on the left. 16R, HPV 16 reference; Ep, European prototype; As, Asian.