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
1The 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.
2Introduction
- 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
3Investigation of effects!
- Cervical Carcinoma (Stage IIIB)
Human Papillomavirus Infection
p53
4Study group
- 52 patients
- Histologically confirmed squamous cell carcinoma
of the uterine cervix - Stage IIIB cervical carcinoma
- Receiving radiation therapy only!
- Time frame 1980-1997
5Pre-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
6Statistical 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
7HPV detection
HPV-1628 patients
HPV-331 patient
HPV-1812 patients
- HPV did not have an apparent influence on any
recurrence
8p53 gene
- 14 tumors with mutation of gene
- Common site of mutation was exon 8
9Survival 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
10Survival Curves according to p53 status
Cause-specific survival
11Recurrence Free Survival/ Local Recurrence Free
Survival
12Connection 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)
13Correlation 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
14Cause-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
15Recurrence 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
16Findings
- 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.
17Discussion
- p53 common in human malignancies
- Agent of carcinogenesis of cervical carcinomaHPV
infection - HPV positivewild type p53
- HPV negativemutant type p53
- Correlation remains controversial
18Cont.
- Results indicate relation of HPV with p53 status
- P53 plays predictive factor in radiation therapy
19QUESTIONS?????????????