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Human Papillomavirus  and Oral Cancer   in Taiwan  Speaker: Ken-Liao Liu Instructors: Prof. Huei Lee, Ya-Wen Cheng Dec. 19, 2008.
 
Oral cancer in Taiwan (Epidemiologic data) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
In the past 20 years…  (Worldwide data) ,[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object]
In the past 20 years: ,[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],Johns Hopkins Kimmel Comprehensive Cancer Center   JNCI 2008 100(6):407-420
[object Object],[object Object],Johns Hopkins Bloomberg School NEJM 2007;356;1944-56
[object Object],[object Object],[object Object]
[object Object]
[object Object],[object Object]
[object Object],[object Object],[object Object]
[object Object],[object Object]
Clinical impact ,[object Object],[object Object]
Clinical impact: HPV effect on tumor staging & treatment ? ,[object Object]
HPV effect on tumor staging & treatment ? ,[object Object],[object Object]
Prevention & Screening? ,[object Object],[object Object]
Prevalence of HPV in Oral Cancer
 
HPV16: 68.2% 86.7% 69.2%
 
 
[object Object],[object Object]
HPV appears to play an etiologic role in many cancers of the oropharynx and possibly a small subgroup of cancers of the oral cavity.  The most common HPV type in genital cancers (HPV16) was also  the most common in these tumors.  The  mechanism  of  transmission of HPV to the oral cavity   warrants further investigation.
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In Taiwan… ,[object Object],[object Object],[object Object],[object Object],[object Object]
Clinical Question: ,[object Object],[object Object],[object Object]
In Taiwan… ,[object Object]
Am J Clin Pathol 2003; 120: 909-916
[object Object],[object Object]
The positive rates : 75%  (69/92) by  nested PCR-based genechips , 53%  (49/92) by  overexpression of p16INK4A  (ISH),   44%  (40/92) by  high-risk HPV  (ISH) Both  overexpression of P16INK4A  and  high-risk HPV  (ISH) positivity were associated with favorable prognoses and  also independent prognostic factors .
aDepartment of Otolaryngology, Chang Gung Memorial Hospital-Kaohsiung Medical Center,  Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan  Oral Oncology,2008, 44(2), 174-179
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
In Taiwan…. ,[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object]
29 OSCC cases 29 controls In situ  PCR ISH
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Our Data:
 
Comparison of HPV16/18 prevalence in tumor sites of cases & controls. 4 (9.1%) 35 (46.1%) Oral Cavity 12 (26.1%) 14 (22.6%) Pharynx Control 16/90 Case 49/138 HPV16 or 18+
 
 
HPV vs Areca-chewing in cases & controls
HPV vs Areca-chewing in cancer cases  Higher HPV16 + in Non-areca-chewing pharyngeal cancer
HPV v.s. P53 in oral cancers: Molecular Classification
p53  mutations in  25 /138
 
 
 
Joint assessment of  p53 /HPV status :  4 biomarker subgroups
Summary: HPV ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Summary: HPV/Areca ,[object Object],[object Object]
Summary: p53 ,[object Object],[object Object],[object Object],[object Object]
Summary ,[object Object],[object Object]
Ongoing/Future Work ,[object Object],[object Object],[object Object]
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Brief Summary ,[object Object],[object Object],[object Object],[object Object],[object Object]
In cancer cases ,[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object]
Clinical Implications of HPV vs HNSCC (OSCC) poorly differentiated Basaloid, advanced stage Histopathology ♂ ♂ =♀ Gender Less sensitive, poor prognosis Sensitive, better prognosis ( Less “field cancerization”) Treatment (R/T , C/T) older - 5 years younger Age ┼ ─ /┼ Tobacco/alcohol ─ ↑ p16 expression ─ ↓ Protein p53 & pRb Mutated Wild type TP53 & Rb1 genes Non-HPV  related HPV  related
Molecular Classification
 
 
 
 
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HPV & Oral Cancer in Taiwan by Dr. Ken Liao Liu 劉耿僚

  • 1. Human Papillomavirus and Oral Cancer in Taiwan Speaker: Ken-Liao Liu Instructors: Prof. Huei Lee, Ya-Wen Cheng Dec. 19, 2008.
  • 2.  
  • 3.
  • 4.
  • 5.
  • 6.
  • 7.
  • 8.
  • 9.
  • 10.
  • 11.
  • 12.
  • 13.
  • 14.
  • 15.
  • 16.
  • 17.
  • 18. Prevalence of HPV in Oral Cancer
  • 19.  
  • 21.  
  • 22.  
  • 23.
  • 24. HPV appears to play an etiologic role in many cancers of the oropharynx and possibly a small subgroup of cancers of the oral cavity. The most common HPV type in genital cancers (HPV16) was also the most common in these tumors. The mechanism of transmission of HPV to the oral cavity warrants further investigation.
  • 25.
  • 26.
  • 27.
  • 28.
  • 29. Am J Clin Pathol 2003; 120: 909-916
  • 30.
  • 31. The positive rates : 75% (69/92) by nested PCR-based genechips , 53% (49/92) by overexpression of p16INK4A (ISH), 44% (40/92) by high-risk HPV (ISH) Both overexpression of P16INK4A and high-risk HPV (ISH) positivity were associated with favorable prognoses and also independent prognostic factors .
  • 32. aDepartment of Otolaryngology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan Oral Oncology,2008, 44(2), 174-179
  • 33.
  • 34.
  • 35.
  • 36. 29 OSCC cases 29 controls In situ PCR ISH
  • 37.
  • 39.  
  • 40. Comparison of HPV16/18 prevalence in tumor sites of cases & controls. 4 (9.1%) 35 (46.1%) Oral Cavity 12 (26.1%) 14 (22.6%) Pharynx Control 16/90 Case 49/138 HPV16 or 18+
  • 41.  
  • 42.  
  • 43. HPV vs Areca-chewing in cases & controls
  • 44. HPV vs Areca-chewing in cancer cases Higher HPV16 + in Non-areca-chewing pharyngeal cancer
  • 45. HPV v.s. P53 in oral cancers: Molecular Classification
  • 46. p53 mutations in 25 /138
  • 47.  
  • 48.  
  • 49.  
  • 50. Joint assessment of p53 /HPV status : 4 biomarker subgroups
  • 51.
  • 52.
  • 53.
  • 54.
  • 55.
  • 56.
  • 57.
  • 58.  
  • 59.  
  • 60.  
  • 61.  
  • 62.  
  • 63.  
  • 64.  
  • 65.  
  • 66.  
  • 67.  
  • 68.
  • 69.
  • 70.
  • 71.
  • 72. Clinical Implications of HPV vs HNSCC (OSCC) poorly differentiated Basaloid, advanced stage Histopathology ♂ ♂ =♀ Gender Less sensitive, poor prognosis Sensitive, better prognosis ( Less “field cancerization”) Treatment (R/T , C/T) older - 5 years younger Age ┼ ─ /┼ Tobacco/alcohol ─ ↑ p16 expression ─ ↓ Protein p53 & pRb Mutated Wild type TP53 & Rb1 genes Non-HPV related HPV related
  • 74.  
  • 75.  
  • 76.  
  • 77.  
  • 78.
  • 79.
  • 80.