Cervical cancer is the most frequent neoplasm of the women in Taiwan and in the world. It influences about 2,700 women and about 1,000 women dying of cervical cancer each year and in Taiwan. Human papilloma viruses (HPV) have been consistently implicated in causing cervical cancer especially those high-risk types have been strongly associated with cervical cancer. From recent years, there is compelling evidence that infection with human papillomavirus (HPV) is a major etiologic factor in the development of cervical intraepithelial neoplasia (CIN) and cervical carcinoma.

As in most virus induced diseases, an adequate immune response is likely to play a key role in clearance of HPV infections and HPV-related lesions. This assumption is born out by both epidemiological studies and animal models. Immune compromised patients such as HIV infected women, organ transplant recipients, and patients suffering other forms of malignancies, are at higher risk of developing CIN lesions and invasive cervical cancer. Moreover, several studies establish the existence of natural HPV E7-specific CTL immunity in humans. Only a minority of women infected with oncogenic HPV types develop CIN or cervical cancer. Indeed, the majority of CIN lesions do not progress or even regress to normal cytology, indicating that other factors such as an inadequate immune function are necessary for the development of progressive CIN lesions and cervical carcinoma.

Consequently, the HLA class I and II phenotype may be correlated with an effective immune response against HPV associated cervical lesions. Differences in the recognition of foreign antigen, such as those contributed by alleles at the HLA class I or II loci, might be proposed to affect the risk of developing cervical cancer.

In the present proposal, we would like to examine the HLA class I and II associations among Taiwanese women with cervical neoplasia. The purposes of this proposal are 1) to address the relationships between the HLA class I and II haplotype and HPV infection, and cervical cancer, 2) to elucidate the immunologic responses to HPV type 16 in different HLA class I and II haplotypes. It will help us to identify which population of HLA genotype are more susceptible to HPV infection and progress to invasive cervical cancer. These results of this research will be very useful for the prevention and screening of cervical cancer in the future.

1. To survey the incidence of HPV infection in CIN and cervical cancer patients Using epidemiologic data drawn from a wide range of countries and population groups, investigators have found evidence of HPV in 90% to 95% of cervical cancers (2). The incidence of HPV in cervical cancer was 79% in our own report (3). Besides, there was 91% of high-grade CIN cases and 50% of low-grade CIN cases could be attributed to HPV infection in Taiwanese women (4). Because thess reports for Taiwanese women were published around 10 years ago. It is important to survey and update the incidence of HPV in CIN and cervical cancer patients in Taiwanese women. We will survey the incidence of HPV infection in 500 cervical cancer patients, 100 patients of CIN and 100 normal population patients.
2. To survey the Human leukocyte antigen (1) haplotype in CIN and cervical cancer patients HLA class I and II alleles have been reported to associate with the nasopharyngeal carcinoma in Taiwan (5) Besides, human leukocyte antigen class I and II alleles might interplay in the response to interferon-alpha treatment in Taiwanese patients with chronic hepatitis C virus infection (6). We will detect the HLA class I and II haplotype first and then correlate them with the CIN and cervical cancer patients.
3. To identify the correlation between HLA class I and II haplotype and HPV infection and CIN and cervical cancer We will further survey the correlation between HLA class I and II and the genotypes of HPV in CIN and cervical cancer patients. We will identify which HLA class I and II haplotypes have positive or negative correlation with HPV infection, CIN and cervical cancer. Then we would determine that which specific HLA antigens are important in determining the risk of HPV infection, CIN and cervical cancer.
4. To elucidate the immunologic responses to HPV type 16 in HLA2 with different II haplotypes and the role of immunogenetics in the carcinogenesis of cervical cancer HPV type 16 has been identified to be the highest incidence of malignant HPV genotypes in cervical cancer. Our laboratory has set up immunologic assays for evaluating the immune responses to HPV type 16 ( please see the preliminary data). We will survey the immune response to HPV type 16 in those HLA class I and II haplotypes which have positive or negative correlation with the HPV infection and cervical cancer. We would identify which population of HLA genotype are more susceptible to HPV infection and invasive cervical cancer and elucidate the role of immunogenetics in the HPV infection and carcinogenesis of cervical cancer.

Accepts Healthy Volunteers

Inclusion Criteria:

- Using epidemiologic data drawn from a wide range of countries and population groups, investigators have found evidence of HPV in 90% to 95% of cervical cancers (2). The incidence of HPV in cervical cancer was 79% in our own report (3). Besides, there was 91% of high-grade CIN cases and 50% of low-grade CIN cases could be attributed to HPV infection in Taiwanese women (4). Because thess reports for Taiwanese women were published around 10 years ago. It is important to survey and update the incidence of HPV in CIN and cervical cancer patients in Taiwanese women. We will survey the incidence of HPV infection in 500 cervical cancer patients, 100 patients of CIN and 100 normal population patients.

Exclusion Criteria:

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