Molecular Epidemiology of Human Papillomavirus Infection and Cervical Neoplasia: Roles of HPV Genotype, Viral Load, Integration and Persistence in the Development of Cervical Neoplasia
Date Issued
2008
Date
2008
Author(s)
Chen, Hui-Chi
Abstract
Cervical cancer is the second common cancer in the world and has been the leading female cancer in Taiwan over than a decade. Human papillomavirus (HPV) is well documented as the necessary cause of cervical cancer. But most previous studies were based on the cross-sectional case-control design, which can neither differentiate transient and persistent infection nor clarify the causal temporality of risk factor exposure and health outcome. The best way to examine the causation between HPV infection and various cancers should be based on a long-term follow-up study with repeated measurement of HPV infection.n this study, 11,923 women were recruited as cohort members from a community-based cancer screening project (CBCSP) since 1991. Participants received health examinations in two bi-annual cycles in 1991-1993 and 1993-1995. After giving their informed consent, cohort members were personally interviewed according to a structured questionnaire to obtain information on socio-demographical characteristics and history of exposures to various cancer risk factors. Virapaps were used to collect cervical cells. Pap smear and health examination were performed. All women with suspected squamous intraepithelial lesions were further examined by colposcopy-guided biopsy to confirm the diagnosis. They were referred to intensive follow-up examinations every four months. The cervical cell samples and Pap smear were collected at baseline and follow-up were tested for HPV DNA by polymerase chain reaction and genotyping by EasyChip. For cohort members infected with HPV types 16, 18, 52 and 58 further tests on viral load and integration into host genome will be carried out. During follow-up, cases of newly-diagnosed cervical cancers and cervical neoplasia will be ascertained through data linkage with profiles of National Cancer Registry and National Death Certification Registry. hrough this long-term follow-up study in CBCSP woman cohort with repeated measurements of HPV infection, we found HPV prevalence was 24.5% and HPV16, 18, 52, 58 and 11 were common types. Among normal women with a mean follow-up duration of 1.4 years, the summarized acquisition rate was 8.4% for any type and the mean of type-specific persistence rate was 27.7%. Women had HPV infection, earlier age at initial coitus, douching use after sexual intercourse, or not currently married had higher risk to acquire newly infection. The determinants for HPV persistence were higher age, high frequency of vaginal delivery, IUD user or post-menopause. With 15-year follow-up, the incidence of cervical cancer for HPV infection and persistence were 171 and 265 per 100000 person-year, the corresponding hazard ratio were 12.8 and 19.6, respectively. HPV16, 18, 52, 58 were the major high-risk types associated with cervical cancer in Taiwan. Around 63% of cervical cancer could be attributed with these 4 types and 51% for HPV16 and/or 18, which vaccine against. In our study, HPV persistence was confirmed the pivotal role in the natural history of cervical cancer with a 44.3-fold risk, once the virus was cleared, the risk was non-significant (HR=2.4, 0.6-9.0). The viral load of HPV16, 18, 52 or 58 associated with persistence in a dose-response relationship and higher viral load (>10^4 copies/ 50ng DNA) was more likely to develop cervical cancer during follow-up; lowering viral load had a protective effect (HR=0.1, 0.03-0.3) with cancer incidence. The integration was associated with cervical neoplasia in the cross-sectional study, however, it couldn’t predict the risks of HPV persistence and cervical cancer in the longitudinal study. he findings will be useful for the primary prevention, early detection and intervention for cervical cancer.
Subjects
HPV
prevalence
acquisition
persistence
viral load
integration
cervical cancer
SDGs
Type
thesis
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