Presented by: Melanie Camacho

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 91:80-89.

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 • P<0.05: significant data

7. HPV detection • HPV-DNA :40/52(76.9%) HPV-16:28 patients HPV-33:1 patient HPV-18:12 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-axis=months 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 (P=0.0004)

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 carcinoma=HPV infection • HPV positive=wild type p53 • HPV negative=mutant type p53 • Correlation remains controversial

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

19. QUESTIONS?????????????