The Effects of p53 Status and Human Papillomavirus Infection on the Clinical Outcome of Patients with Stage IIIB Cervical Carcinoma Treated with Radiation Therapy Alone - PowerPoint PPT Presentation

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The Effects of p53 Status and Human Papillomavirus Infection on the Clinical Outcome of Patients with Stage IIIB Cervical Carcinoma Treated with Radiation Therapy Alone

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Title: The Effects of p53 Status and Human Papillomavirus Infection on the Clinical Outcome of Patients with Stage IIIB Cervical Carcinoma Treated with Radiation Therapy Alone


1
The Effects of p53 Status and Human
Papillomavirus Infection on the Clinical Outcome
of Patients with Stage IIIB Cervical Carcinoma
Treated with Radiation Therapy Alone
  • Presented by Melanie Camacho
  • Ishikawa,H., N. Mitsuhashi, H. Sakurai, K.
    Maebayashi, and H. Niibe. 2001.The Effects of p53
    Status and Human Papillomavirus Infection on the
    Clinical Outcome of Patients with Stage IIIB
    Cervical Carcinoma Treated with Radiation Therapy
    Alone. American Cancer Society 9180-89.

2
Introduction
  • What is p53?
  • Tumor suppressor, present on chromosome 17,
    suggested to regulate the radiosensitivity in
    human malignancies after irradiation
  • Human Papillomavirus Infection-agent of
    carcinogenesis for patients with squamous cell
    carcinoma of the uterine cervix
  • Stage IIIB Cervical Carcinoma-malignant cancer
    growth in the cervical region of the female
    reproductive system

3
Investigation of effects!
  • Cervical Carcinoma (Stage IIIB)

Human Papillomavirus Infection
p53
4
Study group
  • 52 patients
  • Histologically confirmed squamous cell carcinoma
    of the uterine cervix
  • Stage IIIB cervical carcinoma
  • Receiving radiation therapy only!
  • Time frame 1980-1997

5
Pre-Analysis
  • 52 biopsy specimens
  • 70 of tumor cells used
  • DNA extracted and examined for HPV-16, HPV-18,
    HPV-33 by PCR (polymerase chain reaction)
  • p53 examined using nonradioisotope SSCP
    (single-strand conformation polymorphism) analysis

6
Statistical Analysis
  • Utilized t-test or chi-square test
  • Survival time from irradiation initiation to
    death or to last follow-up according to
    Kaplan-Meier method
  • Log rank test used for survival curves
  • Plt0.05 significant data

7
HPV detection
  • HPV-DNA 40/52(76.9)

HPV-1628 patients
HPV-331 patient
HPV-1812 patients
  • HPV did not have an apparent influence on any
    recurrence

8
p53 gene
  • 14 tumors with mutation of gene
  • Common site of mutation was exon 8

9
Survival Rate data
  • Correlation of survival and disease recurrence
    between wild type p53 and mutant type p53 based
    on significant statistics(x-axismonths after
    therapy, y of survivors)
  • Cause-Specific survival
  • Recurrence free survival
  • Local Recurrence Free survival

10
Survival Curves according to p53 status
Cause-specific survival
11
Recurrence Free Survival/ Local Recurrence Free
Survival
12
Connection between HPV infection and p53
  • 34 of 40 HPV positive patients possessed p53 wild
    type
  • 4 of 12 HPV negative patients possessed p53 wild
    type
  • Significant correlation between HPV infection and
    p53 mutant (P0.0004)

13
Correlation of HPV infection and p53 status
  • Division of 4 groups
  • Group A p53 wild type/HPV negative
  • Group B p53 wild type/HPV positive
  • Group C p53 mutant type/HPV negative
  • Group D p53 mutant type/HPV positive

14
Cause-Specific Survival
  • Survival Rates Group A 75.0,Group B
    78.2,Group C 62.5,
  • Group D 44.4
  • No significant difference between groups

15
Recurrence Free Survival/Local Recurrence Free
Survival
5-year recurrence free survival Rates Group A
75.0, Group B 61.8, Group C 50.0, Group D
33.3 Local recurrence free survival Rates
Group A 75.0, Group B 84.0, Group C 62.5,
Group D 50.0
16
Findings
  • Insufficient patients in Group A
  • No significant difference between the groups with
    the cause specific survival
  • Statistical difference between Group B (wild
    type/HPV positive) and Group D (mutant type/HPV
    positive) in free survival rate and local
    recurrence free survival rate.

17
Discussion
  • p53 common in human malignancies
  • Agent of carcinogenesis of cervical carcinomaHPV
    infection
  • HPV positivewild type p53
  • HPV negativemutant type p53
  • Correlation remains controversial

18
Cont.
  • Results indicate relation of HPV with p53 status
  • P53 plays predictive factor in radiation therapy

19
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