Whole-genome analysis of human papillomavirus 67 isolated from Japanese women with cervical lesions

Abstract

Background Human papillomavirus (HPV) type 67 is phylogenetically classified into Alphapapillomavirus species 9 (alpha-9) together with other carcinogenic types (HPV16, 31, 33, 35, 52 and 58), but is the only alpha-9 type defined as possibly carcinogenic. This study aimed to determine whole-genome sequences of HPV67 isolated from Japanese women with cervical cancer or cervical intraepithelial neoplasia (CIN) to better understand the genetic basis of the oncogenic potential of HPV67. Methods Total cellular DNA isolated from cervical exfoliated cells that were single positive for HPV67 (invasive cervical cancer, n = 2; CIN3, n = 6; CIN 2, n = 1; CIN1, n = 2; the normal cervix, n = 1) was subjected to PCR to amplify HPV67 DNA, followed by next generation sequencing to determine the complete viral genome sequences. Variant lineages/sublineages were assigned through viral whole-genome phylogenetic analysis. The transcriptional activity of the virus early promoter was assessed by luciferase reporter assays in cervical cancer cell lines. Results Phylogenetic analyses of HPV67 genomes from Japan (n = 12) revealed that 11 belonged to lineage A (sublineage A1, n = 9; sublineage A2, n = 2) and one belonged to lineage B. All cancer cases contained sublineage A1 variants, and one of these contained an in-frame deletion in the E2 gene. The long control region of the HPV67 genome did not induce transcription from the virus early promoter in HeLa cells, but showed weak transcriptional activity in CaSki cells. Conclusions The single detection of HPV67 in cervical cancer and precancer specimens strongly suggests the carcinogenic potential of this rare genotype. The phylogenetic analysis indicates a predominance of lineage A variants among HPV67 infections in Japan. Since only 23 complete genome sequences of HPV67 had been obtained until now, the newly determined genome sequences in this study are expected to contribute to further functional and evolutionary studies on the genetic diversity of HPV67.

Prevalence and Genotype Distribution of Potential High-Risk and High-Risk Human Papillomavirus among Women attending Selected Reproductive Health Clinics in Lake Victoria Basin-Kenya: A Cross-sectional Study

“…HPV 67, a potential HR HPV was noted as the most prevalent among HIV-positive patients. In a study done among Japanese women with cervical lesions, the genome analysis of HPV 67 suggested the carcinogenic potential of this rare genotype (25). The high prevalence of HPV among HIV-positive patients indicates the need for further clinical and epidemiological follow-up study on the role of other HR and potential HR HPV in cervical diseases especially among immune-compromised population.…”

Prevalence and human papillomavirus (HPV) genotype distribution in Suzhou, China

“… 5 International agency for research on cancer institutions classify HPV16, 18, 31, 33, 39, 45, 51, 52, 56, 58, and 59 as carcinogens (group 1), HPV68 may cause cancer (group 2A), and HPV26, 53, 66, 67, 70, 73, and 82 are classified as being possibly carcinogenic (group 2B). 6 …”