Multiple HPV infection in cervical cancer screened by HPVDNAChip™
Introduction
Cervical cancer is the second most common cancer only to breast cancer in terms of both incidence and mortality worldwide. In Korea, cervical cancer is the third most common female cancer, which accounts for 13.0% of female malignancies [1].
More than 70 types of human papillomavirus have been identified to date and are closely associated with benign and malignant lesions of mucocutaneous epithelia [2]. They have several interesting biological properties, such as host species specificity, preferential site tropism of infection (mucosal or cutaneous), and different pathologies according to genomic diversity [3]. More than 20 genotypes of HPV have been found to infect genitalia and are classified as high or low-risk genotypes based on their oncogenic potentials [4]. Epidemiologic and experimental evidence shows that human papillomaviruses play a major causal role in the development of cervical cancer [5], [6]. By using the polymerase chain reaction, about 90% of cervical cancers have been found to contain DNAs of high-risk HPV-16 or -18, usually the former [2].
Previous studies have shown that HPV-6 and -11 are associated with benign anogenital lesions, whereas HPV-16 and -18 are associated with cervical cancer [7]. Therefore, the association between HPV infections and anogenital lesions is more complicated than expected. HPV types such as HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, and -68 are thought to be high-risk types because they have been identified in high grade intraepithelial lesions or in invasive cervical cancer, whereas HPV-6, -11, -40, -42, -43, -44, and -55 are considered as low-risk types [7], [10]. Geographical differences in HPV types have been reported to exist between countries, and even within the countries such as United States [9], [10]. Therefore, the HPV types prevalent in Japan may differ from those in Western countries [8], [11].
Although a number of studies on the etiologic factors of cervical cancer carried out in Western Europe and North America have suggested that reproductive factors and sexual behavior play important roles in the occurrence cervical cancer, there are few studies to determine the etiological factors of cervical cancer in Korea [12], [13]. As a result of a hospital-based case-control study, Yoo et al. [14] found that the risk factors of cervical cancer in Korea are similar with those found in other countries such as Western Europe and North America.
The HPVDNAChip™ (version 2.0, Biomedlab Co., Seoul, Korea) was recently developed. It is an oligonucleotide chip that enables the rapid and easy detection and genotyping of 15 high-risk and seven low-risk HPV types simultaneously. Using this oligonucleotide chip, we conducted this case-control study in Korea to elucidate the distribution of high-risk HPV type infection in cervical cancer and to examine the prevalence of infection of a single HPV type or of multiple HPV types to clarify the association between HPV infection pattern and cervical cancer. The associations between HPV infection and various risk factors of cervical cancer were also examined.
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Study subjects
Of first-visit outpatients for the detection or the diagnosis of uterine cervical cancer at the Department of Obstetrics and Gynecology in Seoul National University Hospital between September 1992 and May 1995, women under the age of 60, with an intact uterus, and who had received both the Pap smear test and a direct interview were eligible (n=826). Histological confirmation was carried out for those who had ASCUS or more by the Pap smear test. Eighty cases were eligible and were enrolled in
Results
The risk of cervical cancer was increased for women with a family history of cervical cancer (adjusted OR=2.3, 95% CI: 0.92–6.17) and for smokers (adjusted OR=3.2, 95% CI: 1.45–7.06). We also found a trend of increased risk with the number of full term pregnancies Body mass index was not significantly associated with the risk of cervical cancer (Table 1).
High-risk type HPV infections were found in only 7.2% (54 of 746) of the control, while 54.5% (six of 11), and 76.5% (52 of
Discussion
This study was conducted to determine the distribution of high-risk HPV type infection in cervical cancer and to examine the prevalence of infection with in a single HPV type or with multiple HPV types, as a means of clarifying the association between the HPV infection pattern and cervical cancer using newly developed oligonucleotide chips (HPVDNAChips™).
The HPVDNAChip method identifies 15 high-risk groups (16/18/31/33/35/39/45/51/52/56/58/59/66/68/69) and seven low-risk groups
Acknowledgements
This study was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (Grant No.: 02-PJ1-PG1-21400-0001).
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