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Trial Title:
The Correlations Between HPV L1-Specific Immunologic Responses in Cervical Cancer and Cervical Intraepithelial Neoplasia (CIN) Patients and Their Prognosis
NCT ID:
NCT00728871
Condition:
Cervical Cancer
Cervical Intraepithelial Neoplasia
Conditions: Official terms:
Uterine Cervical Neoplasms
Neoplasms
Carcinoma in Situ
Uterine Cervical Dysplasia
Conditions: Keywords:
cervical cancer, HPV, immunity
Study type:
Interventional
Study phase:
N/A
Overall status:
Unknown status
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Basic Science
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
peripheral blood isolation
Description:
To isolate serum from patient peripheral blood to test the titer of HPV infection and
cytokine expression
Summary:
A. To investigate the relationship between serum titer of anti-HPV16 antibody and
clinicopathological factors of cervical cancer patients.
B. To investigate that if the serum titer of anti-HPV16 antibody could be a prognostic
factor in the cervical cancer patients.
C. To investigate the serum titer of anti-HPV16 antibody in HPV16-infected populations
with various disease status such as infection only, precancerous lesion, and early and
advanced cervical cancer.
Detailed description:
Cervical cancer is the most frequent neoplasm of the women in Taiwan and in the world.
Cervical cancer affects half a million women each year and results in about 200,000
worldwide and it also influences about 2,700 women and about 1,000 women dying of
cervical cancer each year and in Taiwan. There is strong evidence suggesting that this
cancer is 100% attributable to infection with certain types of human papillomavirus
(HPV); in fact, the World Health Organization (WHO) has very recently recognized that
this cancer is caused by HPV. There are around 100 different HPV-types, of which around
40 types infecting the anogenital tract and causing cervical lesions and cervical cancer
have been called High Risk HPV (i.e., HR-HPV-16, -18, -31, -33, and -58). 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-specific immunity in
humans. Immune responses of the host are indeed critical in the virus-related infectious
diseases. The immune response against HPV antigens is Human leukocyte antigen restricted.
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. Studies by different
groups on associations between certain HLA alleles and susceptibility to, or protection
against CIN lesions and cervical carcinoma, reveal varying conclusions and warrant
further research.
Most potentially oncogenic, persistent, long-term HPV infections induce an antibody
response against virus proteins which can be detected by ELISA test and can be a good
indicator of past as well as current infections and chronic active infection, associated
with the presence of cervical lesions and the high risk of acquiring cervical cancer. In
fact, it has been reported that women who are seropositive for HPV-16 present a higher
risk of developing cervical carcinoma than seronegative women. L1-viral capsid proteins
are one of the targets for antibodies induced by persistent HPV genital infection.
The L1 protein represents more than 90% of the total protein on the surface of the virus.
This protein is able to assemble itself, forming virus-like particles (VLPs). VLPs,
mainly type 16, have been broadly used for studying the antibody response induced by
genital HPVinfection. The VLP-antibody presence is stable in time, correlated with the
number of sexual partners, and associated with persistent infection, viral load, and
development of neoplasic lesions; this is rarely found in patients suffering from
transitory infections. Seropositivity occurs more frequently in patients who have
progressed to CIN III and invasive cancer than in those suffering from CIN I or CIN II
and the antibody response is significantly higher in women having a higher viral load
than those with lower viral load. Prospective studies have shown that 70-90% of HPV-16
infected women are seroconverted between 6 and 18 months after HPV DNA has been detected
and that this rarely occurs in patients detected as having transient HPV DNA.
However, other serological studies have shown that 20-50% of women suffering from
HPV-associated lesions, with HPV DNA presence, do not present detectable levels of
anti-VLP antibodies; this is in part due to the lack of an optimized test and the fact
that these antibodies reactivity is type-specific for the virus. An optimized VLP-based
ELISA test has been recently reported showing 93% sensitivity and 98.5% specificity for
discriminating between positive and negative control sera. However, there was no report
to evaluate the antibody response in patients with HPV-infected cervical lesions and with
the prognosis of these patients.
So in the present proposal, we would like to examine the anti-L1 antibodies of various
HPV types among Taiwanese women with HPV-related CIN or cervical cancer. The purposes of
this proposal are 1) to address the immunologic responses to HPV between CIN and cervical
cancer patients. , 2) to elucidate the correlation between immunologic responses to HPV
and disease severity of cervical cancer., 3) to evaluate the correlation between
immunologic responses to HPV and the prognosis of cervical cancer patients.
The samples of patients' sera were collected on the day of surgery. 2. The sera samples
were freezedon -200C until analyzed. 3. The sera samples will be shipped to the Lab. of
Merck company in US. 4. HPV Serologic Assay A competitive radioimmunoassay developed by
Merck Research Laboratories will be was used and perform to quantitate serum HPV- 6, 11,
16, 18, 31, 33, 45, 51, 52, 58, 59, or 68 antibodies in Merck Research Laboratories (12).
Results will be read from a standard curve, corrected for dilution, and reported in
arbitrary units (milli-Merck Units, or mMU per milliliter). A fixed cutoff of 5.9 mMU per
milliliter (derived by repeatedly testing a panel of positive and negative samples
against the standard curve) will be used to determine the HPV-6, 11, 16, 18, 31, 33, 45,
51, 52, 58, 59, or 68 serologic status of the women.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. cervical intrapeithelial neoplasm
2. Cervical cancer
Exclusion Criteria:
Gender:
Female
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Natioanal Taiwan Univ. Hospital
Address:
City:
Taipei
Zip:
100
Country:
China
Status:
Recruiting
Contact:
Last name:
Chi-An Chen, MD
Phone:
886-2-2312-3456
Phone ext:
5166
Email:
cachen@ha.mc.ntu.edu.tw
Start date:
December 2005
Completion date:
December 2011
Lead sponsor:
Agency:
National Taiwan University Hospital
Agency class:
Other
Source:
National Taiwan University Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT00728871