Genotyping of 22 human papillomavirus types by DNA chip in Korean women: Comparison with cytologic diagnosis

Abstract

OBJECTIVE: More sensitive and reliable methods than individual testing (such as polymerase chain reaction, restriction fragment length polymorphism, and Southern blot) should be developed as screening tools for the detection of latent human papillomavirus. Today, the new Bethesda system recommends human papillomavirus testing as an adjuvant to the conventional Papanicolaou smear for more comprehensive identification of women at certain risk of cervical neoplasia. We performed human papillomavirus genotyping with the newly designed human papillomavirus DNA chip, which is based on polymerase chain reaction for high-throughput screening power, and compared the results with the results of a Papanicolaou smear according to the new Bethesda system.

STUDY DESIGN: Polymerase chain reaction amplifications of the human papillomavirus L1 region from biologic samples were hybridized to silanized glass slides by a microarrayer, which comprised 22 specific oligonucleotide probes to their genotypes, consisting of 15 high-risk and 7 low-risk types. Two cervical cancer cell lines and 20 plasmids that contained each type of the human papillomavirus whole genome were used for the evaluation of this method; in all cases, the cancer cell lines and plasmids showed clear positive signals on their corresponding positions. A comparative study that used 685 cervicovaginal swabs was performed by human papillomavirus DNA chip microarray together with Papanicolaou diagnosis.

RESULTS: Human papillomavirus was identified as positive in 31.9% of the 414 control samples and in 78.6% of the 271 neoplastic lesions. The major prevailing human papillomavirus genotypes were human papillomavirus types 16, 58, and 18, in descending order of incidence (average overall, 78.8%). Almost all of the remaining cases were comprised of human papillomavirus types 39, 52, 56, and 51. The frequency of multiple infection of human papillomavirus was highest in low-grade squamous intraepithelial lesion but was lowest in squamous cell carcinoma. All cases that exhibited infection of single human papillomavirus type 58 were squamous cell carcinoma.

CONCLUSION: Human papillomavirus types 16, 18, and 58 were confirmed to be major causative factors for cervical carcinogenesis. Low-grade squamous intraepithelial lesion is a heterogeneous entity that is composed of different human papillomavirus subtypes and prevails in younger women (<40 years old). The human papillomavirus chip has potential use as a high-throughput screening test.