Assessment of human papilloma virus-related disease

• US 7,879,546 B2
• Filed: 03/02/2007
• Issued: 02/01/2011
• Est. Priority Date: 12/12/1997
• Status: Expired due to Fees

• Current Assignee: QIAGEN Gaithersburg, Inc. (Qiagen NV)
• Original Assignee: QIAGEN Gaithersburg, Inc. (Qiagen NV)
• Inventors: Lazar, James G., Lorincz, Attila T.
• Primary Examiner(s): Johannsen; Diana B
• Application Number:
  US11/681,539
• Publication Number:
  US 20070154884A1
• Time in Patent Office: 1,432 Days
• Field of Search: None
• US Class Current: 435/5
• CPC Class Codes: A01N 1/021 Preservation or perfusion media, liquids, solids or gases used in the preservation of cells, tissue, organs or bodily fluids
• CPC Class Codes: C12Q 1/6806 Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 1/708 for papilloma
• CPC Class Codes: C12Q 2523/101 Crosslinking agents, e.g. psoralen
• CPC Class Codes: C12Q 2543/10 the purpose being "in situ" analysis
• CPC Class Codes: C12Q 2545/114 involving a quantitation step
• CPC Class Codes: C12Q 2600/112 Disease subtyping, staging or classification
• CPC Class Codes: C12Q 2600/118 Prognosis of disease development

Abstract

This invention provides methods for assessing HPV infection. Gene expression levels are used to assess the progression of HPV infection from benign to malignant growth. Also provided are kits for carrying out the methods of this invention.

Claims

1. A method of diagnosing risk of HPV 18-induced neoplasia comprising the steps of:

quantifying a first level of one or more HPV 18 mRNA from a sample collected from a patient infected with HPV, wherein the one or more HPV 18 mRNA is selected from the group consisting of E2 mRNA, E4 mRNA, E6 mRNA, and E7 mRNA;

quantifying a second level of one or more HPV 18 mRNA from a sample collected from said patient, wherein the one or more HPV 18 mRNA is selected from the group consisting of E2 mRNA, L1 mRNA, and L2 mRNA; and

determining a ratio of the quantified first and second levels of HPV 18 mRNA, wherein the ratio is selected from the group consisting of (E6+E7)/L1, (E6+E7)/(L1+L2), (E2+E4+E6+E7)/(L1+L2), and (E6+E7)/E2,

wherein a ratio of greater than 2 is indicative of HPV 18-induced cell transformation and risk of neoplasia.

2. The method of diagnosing risk of HPV 18-induced neoplasia of claim 1, wherein the determined ratio is (E6+E7)/L1.

3. The method of diagnosing risk of HPV 18-induced neoplasia of claim 1, wherein the determined ratio is (E6+E7)/(L1+L2).

4. The method of diagnosing risk of HPV 18-induced neoplasia of claim 1, wherein the determined ratio is (E2+E4+E6+E7)/(L1+L2).

5. The method of diagnosing risk of HPV 18-induced neoplasia of claim 1, wherein the determined ratio is (E6+E7)/E2.

6. A method of diagnosing the onset of HPV 18-induced neoplasia comprising the steps of:

quantifying a level of a group 1 HPV 18 mRNA from a sample collected from a patient infected with HPV 18;

quantifying a level of a group 2 HPV 18 mRNA from a sample collected from said patient; and

determining a ratio of the quantified levels of the group 1 mRNA to group 2 mRNA,

wherein a ratio of greater than 2 is indicative of HPV 18-induced neoplastic onset.

7. A method of diagnosing the risk or onset of HPV 18-induced neoplasia comprising the steps of:

quantifying a level of a group 1 HPV 18 mRNA from a sample collected from a patient infected with HPV 18;

quantifying a level of a group 3 HPV 18 mRNA from a sample collected from said patient; and

determining a ratio of the quantified levels of the group 1 mRNA to group 3 mRNA,

wherein a ratio of greater than 2 is indicative of high risk or onset of HPV 18-induced neoplastic onset.

8. A method of diagnosing the risk or onset of HPV 18-induced neoplasia comprising the steps of:

quantifying a level of a group 1 HPV 18 mRNA from a sample collected from a patient infected with HPV 18;

quantifying a level of a group 2 HPV 18 mRNA from a sample collected from said patient;

quantifying a level of a group 3 HPV 18 mRNA from a sample collected from said patient; and

determining a ratio of the quantified level of the group 1 mRNA to the sum of the quantified levels of the group 2 mRNA and the group 3 mRNA,

wherein a ratio of greater than 2 is indicative of high risk or onset of HPV 18-induced neoplastic onset.

9. A method of diagnosing a stage of HPV 18-induced disease comprising the steps of:

quantifying a first level of one or more HPV 18 mRNA from a sample collected from a patient infected with HPV 18, wherein the one or more HPV 18 mRNA is selected from the group consisting of E6 mRNA and E7 mRNA;

quantifying a second level of one or more HPV 18 mRNA from a sample collected from said patient, wherein the one or more HPV 18 mRNA is selected from the group consisting of L1 mRNA, L2 mRNA, and E2 mRNA; and

determining a ratio of the quantified first and second levels of HPV 18 mRNA, wherein the ratio is selected from the group consisting of E6/L1, E6/L2, E6/E2, E6/(L1+L2), E6/(L1+E2), E6/(L2+E2), E6/(L1+L2+E2), E7/L1, E7/L2, E7/E2, E7/(L1+L2), E7/(L1+E2), E7/(L2+E2), E7/(L1+L2+E2), (E6+E7)/L1, (E6+E7)/L2, (E6+E7)/E2, (E6+E7)/(L1+L2), (E6+E7)/(L1+E2), (E6+E7)/(L2+E2), and (E6+E7)/(L1+L2+E2),

wherein any ratio of greater than 2 is indicative of early stage HPV 18-induced disease, thereby diagnosing a stage of HPV 18-induced disease in a patient infected with HPV.

10. The method of diagnosing a stage of HPV 18-induced disease of claim 9, wherein the determined ratio is E6/L1.

11. The method of diagnosing a stage of HPV 18-induced disease of claim 9, wherein the determined ratio is E6/L2.

12. The method of diagnosing a stage of HPV 18-induced disease of claim 9, wherein the determined ratio is E6/E2.

13. The method of diagnosing a stage of HPV 18-induced disease of claim 9, wherein the determined ratio is E6/(L1+L2).

14. The method of diagnosing a stage of HPV 18-induced disease of claim 9, wherein the determined ratio is E6/(L1+E2).

15. The method of diagnosing a stage of HPV 18-induced disease of claim 9, wherein the determined ratio is E6/(L2+E2).

16. The method of diagnosing a stage of HPV 18-induced disease of claim 9, wherein the determined ratio is E6/(L1+L2+E2).

17. The method of diagnosing a stage of HPV 18-induced disease of claim 9, wherein the determined ratio is E7/L1.

18. The method of diagnosing a stage of HPV 18-induced disease of claim 9, wherein the determined ratio is E7/L2.

19. The method of diagnosing a stage of HPV 18-induced disease of claim 9, wherein the determined ratio is E7/E2.

20. The method of diagnosing a stage of HPV 18-induced disease of claim 9, wherein the determined ratio is E7/(L1+L2).

21. The method of diagnosing a stage of HPV 18-induced disease of claim 9, wherein the determined ratio is E7/(L1+E2).

22. The method of diagnosing a stage of HPV 18-induced disease of claim 9, wherein the determined ratio is E7/(L2+E2).

23. The method of diagnosing a stage of HPV 18-induced disease of claim 9, wherein the determined ratio is E7/(L1+L2+E2).

24. The method of diagnosing a stage of HPV 18-induced disease of claim 9, wherein the determined ratio is (E6+E7)/L1.

25. The method of diagnosing a stage of HPV 18-induced disease of claim 9, wherein the determined ratio is (E6+E7)/L2.

26. The method of diagnosing a stage of HPV 18-induced disease of claim 9, wherein the determined ratio is (E6+E7)/E2.

27. The method of diagnosing a stage of HPV 18-induced disease of claim 9, wherein the determined ratio is (E6+E7)/(L1+L2).

28. The method of diagnosing a stage of HPV 18-induced disease of claim 9, wherein the determined ratio is (E6+E7)/(L1+E2).

29. The method of diagnosing a stage of HPV 18-induced disease of claim 9, wherein the determined ratio is (E6+E7)/(L2+E2).

30. The method of diagnosing a stage of HPV 18-induced disease of claim 9, wherein the determined ratio is (E6+E7)/(L1+L2+E2).

31. A method of diagnosing HPV 18-induced cancer comprising the steps of:

quantifying a first level of one or more HPV 18 mRNA from a sample collected from a patient infected with HPV, wherein the one or more HPV 18 mRNA is selected from the group consisting of E6 mRNA and E7 mRNA;

quantifying a second level of one or more HPV 18 mRNA from said patient, wherein the one or more HPV 18 mRNA is selected from the group consisting of E2 mRNA, E4 mRNA, L1 mRNA and L2 mRNA; and

determining a ratio of the quantified first and second levels of HPV 18 mRNA, wherein the ratio is selected from the group consisting of (E6+E7)/L1, (E6+E7)/(L1+L2), and (E6+E7)/(E2+E4),

wherein a ratio of greater than 4 is indicative of HPV 18-induced cancer.

32. The method of diagnosing HPV 18-induced cancer of claim 31, wherein the determined ratio is (E6+E7)/L1.

33. The method of diagnosing HPV 18-induced cancer of claim 31, wherein the determined ratio is (E6+E7)/(L1+L2).

34. The method of diagnosing HPV 18-induced cancer of claim 31, wherein the determined ratio is (E6+E7)/(E2+E4).

35. A method of diagnosing the risk or onset of HPV 18-induced cancer comprising the steps of:

quantifying a group 1 HPV 18 mRNA from a sample collected from a patient infected with HPV;

quantifying a group 2 HPV 18 mRNA from a sample collected from a patient infected with HPV; and

determining a ratio of group 1 mRNA level to group 2 mRNA level;

wherein any ratio of greater than 4 is indicative of high risk or onset of HPV 18-induced cancer.

36. A method of diagnosing the risk or onset of HPV 18-induced cancer comprising the steps of:

quantifying a group 1 HPV 18 mRNA from a sample collected from a patient infected with HPV;

quantifying a group 3 HPV 18 mRNA from a sample collected from a patient infected with HPV; and

determining a ratio of group 1 mRNA level to group 3 mRNA level;

wherein any ratio of greater than 4 is indicative of high risk or onset of HPV 18-induced cancer.

37. A method of diagnosing risk of HPV 31-induced neoplasia comprising the steps of:

quantifying a first level of one or more HPV 31 mRNA from a sample collected from a patient infected with HPV, wherein the one or more HPV 31 mRNA is selected from the group consisting of E2 mRNA, E4 mRNA, E6 mRNA, and E7 mRNA;

quantifying a second level of one or more HPV 31 mRNA from a sample collected from said patient, wherein the one or more HPV 31 mRNA is selected from the group consisting of E2 mRNA, L1 mRNA, and L2 mRNA; and

determining a ratio of the quantified first and second levels of HPV 31 mRNA, wherein the ratio is selected from the group consisting of (E6+E7)/L1, (E6+E7)/(L1+L2), (E2+E4+E6+E7)/(L1+L2), and (E6+E7)/E2,

wherein a ratio of greater than 2 is indicative of HPV 31-induced cell transformation and risk of neoplasia.

38. The method of diagnosing risk of HPV 31-induced neoplasia of claim 37, wherein the determined ratio is (E6+E7)/L1.

39. The method of diagnosing risk of HPV 31-induced neoplasia of claim 37, wherein the determined ratio is (E6+E7)/(L1+L2).

40. The method of diagnosing risk of HPV 31-induced neoplasia of claim 37, wherein the determined ratio is (E2+E4+E6+E7)/(L1+L2).

41. The method of diagnosing risk of HPV 31-induced neoplasia of claim 37, wherein the determined ratio is (E6+E7)/E2.

42. A method of diagnosing the onset of HPV 31-induced neoplasia comprising the steps of:

quantifying a level of a group 1 HPV 31 mRNA from a sample collected from a patient infected with HPV31;

quantifying a level of a group 2 HPV 31 mRNA from a sample collected from said patient; and

determining a ratio of the quantified levels of the group 1 mRNA to group 2 mRNA,

wherein a ratio of greater than 2 is indicative of HPV 31-induced neoplastic onset.

43. A method of diagnosing the risk or onset of HPV 31-induced neoplasia comprising the steps of:

quantifying a level of a group 1 HPV 31 mRNA from a sample collected from a patient infected with HPV31;

quantifying a level of a group 3 HPV 31 mRNA from a sample collected from said patient; and

determining a ratio of the quantified levels of the group 1 mRNA to group 3 mRNA,

wherein a ratio of greater than 2 is indicative of high risk or onset of HPV 31-induced neoplastic onset.

44. A method of diagnosing the risk or onset of HPV 31-induced neoplasia comprising the steps of:

quantifying a level of a group 1 HPV 31 mRNA from a sample collected from a patient infected with HPV31;

quantifying a level of a group 2 HPV 31 mRNA from a sample collected from said patient;

quantifying a level of a group 3 HPV 31 mRNA from a sample collected from said patient; and

determining a ratio of the quantified level of the group 1 mRNA to the sum of the quantified levels of the group 2 mRNA and the group 3 mRNA,

wherein a ratio of greater than 2 is indicative of high risk or onset of HPV 31-induced neoplastic onset.

45. A method of diagnosing a stage of HPV 31-induced disease comprising the steps of:

quantifying a first level of one or more HPV 31 mRNA from a sample collected from a patient infected with HPV 31, wherein the one or more HPV 31 mRNA is selected from the group consisting of E6 mRNA and E7 mRNA;

quantifying a second level of one or more HPV 31 mRNA from a sample collected from said patient, wherein the one or more HPV 31 mRNA is selected from the group consisting of L1 mRNA, L2 mRNA, and E2 mRNA; and

determining a ratio of the quantified first and second levels of HPV 31 mRNA, wherein the ratio is selected from the group consisting of E6/L1, E6/L2, E6/E2, E6/(L1+L2), E6/(L1+E2), E6/(L2+E2), E6/(L1+L2+E2), E7/L1, E7/L2, E7/E2, E7/(L1+L2), E7/(L1+E2), E7/(L2+E2), E7/(L1+L2+E2), (E6+E7)/L1, (E6+E7)/L2, (E6+E7)/E2, (E6+E7)/(L1+L2), (E6+E7)/(L1+E2), (E6+E7)/(L2+E2), and (E6+E7)/(L1+L2+E2),

wherein any ratio of greater than 2 is indicative of early stage HPV 31-induced disease, thereby diagnosing a stage of HPV 31-induced disease in a patient infected with HPV.

46. The method of diagnosing a stage of HPV 31-induced disease of claim 45, wherein the determined ratio is E6/L1.

47. The method of diagnosing a stage of HPV 31-induced disease of claim 45, wherein the determined ratio is E6/L2.

48. The method of diagnosing a stage of HPV 31-induced disease of claim 45, wherein the determined ratio is E6/E2.

49. The method of diagnosing a stage of HPV 31-induced disease of claim 45, wherein the determined ratio is E6/(L1+L2).

50. The method of diagnosing a stage of HPV 31-induced disease of claim 45, wherein the determined ratio is E6/(L1+E2).

51. The method of diagnosing a stage of HPV 31-induced disease of claim 45, wherein the determined ratio is E6/(L2+E2).

52. The method of diagnosing a stage of HPV 31-induced disease of claim 45, wherein the determined ratio is E6/(L1+L2+E2).

53. The method of diagnosing a stage of HPV 31-induced disease of claim 45, wherein the determined ratio is E7/L1.

54. The method of diagnosing a stage of HPV 31-induced disease of claim 45, wherein the determined ratio is E7/L2.

55. The method of diagnosing a stage of HPV 31-induced disease of claim 45, wherein the determined ratio is E7/E2.

56. The method of diagnosing a stage of HPV 31-induced disease of claim 45, wherein the determined ratio is E7/(L1+L2).

57. The method of diagnosing a stage of HPV 31-induced disease of claim 45, wherein the determined ratio is E7/(L1+L2).

58. The method of diagnosing a stage of HPV 31-induced disease of claim 45, wherein the determined ratio is E7/(L2+E2).

59. The method of diagnosing a stage of HPV 31-induced disease of claim 45, wherein the determined ratio is E7/(L1+L2+E2).

60. The method of diagnosing a stage of HPV 31-induced disease of claim 45, wherein the determined ratio is (E6+E7)/L1.

61. The method of diagnosing a stage of HPV 31-induced disease of claim 45, wherein the determined ratio is (E6+E7)/L2.

62. The method of diagnosing a stage of HPV 31-induced disease of claim 45, wherein the determined ratio is (E6+E7)/E2.

63. The method of diagnosing a stage of HPV 31-induced disease of claim 45, wherein the determined ratio is (E6+E7)/(L1+L2).

64. The method of diagnosing a stage of HPV 31-induced disease of claim 45, wherein the determined ratio is (E6+E7)/(L1+E2).

65. The method of diagnosing a stage of HPV 31-induced disease of claim 45, wherein the determined ratio is (E6+E7)/(L2+E2).

66. The method of diagnosing a stage of HPV 31-induced disease of claim 45, wherein the determined ratio is (E6+E7)/(L1+L2+E2).

67. A method of diagnosing HPV 31-induced cancer comprising the steps of:

quantifying a first level of one or more HPV 31 mRNA from a sample collected from a patient infected with HPV, wherein the one or more HPV 31 mRNA is selected from the group consisting of E6 mRNA and E7 mRNA;

quantifying a second level of one or more HPV 31 mRNA from said patient, wherein the one or more HPV 31 mRNA is selected from the group consisting of E2 mRNA, E4 mRNA, L1 mRNA and L2 mRNA; and

determining a ratio of the quantified first and second levels of HPV 31 mRNA, wherein the ratio is selected from the group consisting of (E6+E7)/L1, (E6+E7)/(L1+L2), and (E6+E7)/(E2+E4),

wherein a ratio of greater than 4 is indicative of HPV 31-induced cancer.

68. The method of diagnosing HPV 31-induced cancer of claim 67, wherein the determined ratio is (E6+E7)/L1.

69. The method of diagnosing HPV 31-induced cancer of claim 67, wherein the determined ratio is (E6+E7)/(L1+L2).

70. The method of diagnosing HPV 31-induced cancer of claim 67, wherein the determined ratio is (E6+E7)/(E2+E4).

71. A method of diagnosing the risk or onset of HPV 31-induced cancer comprising the steps of:

quantifying a group 1 HPV 31 mRNA from a sample collected from a patient infected with HPV;

quantifying a group 2 HPV31 mRNA from a sample collected from a patient infected with HPV; and

determining a ratio of group 1 mRNA level to group 2 mRNA level;

wherein any ratio of greater than 4 is indicative of high risk or onset of HPV 31-induced cancer.

72. A method of diagnosing the risk or onset of HPV 31-induced cancer comprising the steps of:

quantifying a group 1 HPV 31 mRNA from a sample collected from a patient infected with HPV;

quantifying a group 3 HPV 31 mRNA from a sample collected from a patient infected with HPV; and

determining a ratio of group 1 mRNA level to group 3 mRNA level;

wherein any ratio of greater than 4 is indicative of high risk or onset of HPV 31-induced cancer.

73. A method of diagnosing risk of HPV 16-induced neoplasia comprising the steps of:

quantifying a first level of one or more HPV 16 mRNA from a sample collected from a patient infected with HPV, wherein the one or more HPV 16 mRNA is selected from the group consisting of E2 mRNA, E4 mRNA, E6 mRNA, and E7 mRNA;

quantifying a second level of one or more HPV 16 mRNA from a sample collected from said patient, wherein the one or more HPV 16 mRNA is selected from the group consisting of E2 mRNA, L1 mRNA, and L2 mRNA; and

determining a ratio of the quantified first and second levels of HPV 16 mRNA, wherein the ratio is selected from the group consisting of (E6+E7)/L1, (E6+E7)/(L1+L2), (E2+E4+E6+E7)/(L1+L2), (E6+E7)/E2,

wherein a ratio of greater than 2 is indicative of HPV 16-induced cell transformation and risk of neoplasia.

74. The method of diagnosing risk of HPV 16-induced neoplasia of claim 73, wherein the determined ratio is (E6+E7)/L1.

75. The method of diagnosing risk of HPV 16-induced neoplasia of claim 73, wherein the determined ratio is (E6+E7)/(L1+L2).

76. The method of diagnosing risk of HPV 16-induced neoplasia of claim 73, wherein the determined ratio is (E2+E4+E6+E7)/(L1+L2).

77. The method of diagnosing risk of HPV 16-induced neoplasia of claim 73, wherein the determined ratio is (E6+E7)/E2.

78. A method of diagnosing the onset of HPV 16-induced neoplasia comprising the steps of:

quantifying a level of a group 1 HPV 16 mRNA from a sample collected from a patient infected with HPV16;

quantifying a level of a group 2 HPV 16 mRNA from a sample collected from said patient; and

determining a ratio of the quantified levels of the group 1 mRNA to group 2 mRNA,

wherein a ratio of greater than 2 is indicative of HPV 16-induced neoplastic onset.

79. A method of diagnosing the risk or onset of HPV 16-induced neoplasia comprising the steps of:

quantifying a level of a group 1 HPV 16 mRNA from a sample collected from a patient infected with HPV16;

quantifying a level of a group 3 HPV 16 mRNA from a sample collected from said patient; and

determining a ratio of the quantified levels of the group 1 mRNA to group 3 mRNA,

wherein a ratio of greater than 2 is indicative of high risk or onset of HPV 16-induced neoplastic onset.

80. A method of diagnosing the risk or onset of HPV 16-induced neoplasia comprising the steps of:

quantifying a level of a group 1 HPV 16 mRNA from a sample collected from a patient infected with HPV16;

quantifying a level of a group 2 HPV 16 mRNA from a sample collected from said patient;

quantifying a level of a group 3 HPV 16 mRNA from a sample collected from said patient; and

determining a ratio of the quantified level of the group 1 mRNA to the sum of the quantified levels of the group 2 mRNA and the group 3 mRNA,

wherein a ratio of greater than 2 is indicative of high risk or onset of HPV 16-induced neoplastic onset.

81. A method of diagnosing a stage of HPV 16-induced disease comprising the steps of:

quantifying a first level of one or more HPV 16 mRNA from a sample collected from a patient infected with HPV 16, wherein the one or more HPV 16 mRNA is selected from the group consisting of E6 mRNA and E7 mRNA;

quantifying a second level of one or more HPV 16 mRNA from a sample collected from said patient, wherein the one or more mRNA is selected from the group consisting of L1 mRNA, L2 mRNA, and E2 mRNA; and

determining a ratio of the quantified first and second levels of HPV 16 mRNA, wherein the ratio is selected from the group consisting of E6/L1, E6/L2, E6/E2, E6/(L1+L2), E6/(L1+E2), E6/(L2+E2), E6/(L1+L2+E2), E7/L1, E7/L2, E7/E2, E7/(L1+L2), E7/(L1+E2), E7/(L2+E2), E7/(L1+L2+E2), (E6+E7)/L1, (E6+E7)/L2, (E6+E7)/E2, (E6+E7)/(L1+L2), (E6+E7)/(L1+E2), (E6+E7)/(L2+E2), and (E6+E7)/(L1+L2+E2),

wherein any ratio of greater than 2 is indicative of early stage HPV 16-induced disease, thereby diagnosing a stage of HPV 16-induced disease in a patient infected with HPV.

82. The method of diagnosing a stage of HPV 16-induced disease of claim 81, wherein the determined ratio is E6/L1.

83. The method of diagnosing a stage of HPV 16-induced disease of claim 81, wherein the determined ratio is E6/L2.

84. The method of diagnosing a stage of HPV 16-induced disease of claim 81, wherein the determined ratio is E6/E2.

85. The method of diagnosing a stage of HPV 16-induced disease of claim 81, wherein the determined ratio is E6/(L1+L2).

86. The method of diagnosing a stage of HPV 16-induced disease of claim 81, wherein the determined ratio is E6/(L1+E2).

87. The method of diagnosing a stage of HPV 16-induced disease of claim 81, wherein the determined ratio is E6/(L2+E2).

88. The method of diagnosing a stage of HPV 16-induced disease of claim 81, wherein the determined ratio is E6/(L1+L2+E2).

89. The method of diagnosing a stage of HPV 16-induced disease of claim 81, wherein the determined ratio is E7/L1.

90. The method of diagnosing a stage of HPV 16-induced disease of claim 81, wherein the determined ratio is E7/L2.

91. The method of diagnosing a stage of HPV 16-induced disease of claim 81, wherein the determined ratio is E7/E2.

92. The method of diagnosing a stage of HPV 16-induced disease of claim 81, wherein the determined ratio is E7/(L1+L2).

93. The method of diagnosing a stage of HPV 16-induced disease of claim 81, wherein the determined ratio is E7/(L1+E2).

94. The method of diagnosing a stage of HPV 16-induced disease of claim 81, wherein the determined ratio is E7/(L2+E2).

95. The method of diagnosing a stage of HPV 16-induced disease of claim 81, wherein the determined ratio is E7/(L1+L2+E2).

96. The method of diagnosing a stage of HPV 16-induced disease of claim 81, wherein the determined ratio is (E6+E7)/L1.

97. The method of diagnosing a stage of HPV 16-induced disease of claim 81, wherein the determined ratio is (E6+E7)/L2.

98. The method of diagnosing a stage of HPV 16-induced disease of claim 81, wherein the determined ratio is (E6+E7)/E2.

99. The method of diagnosing a stage of HPV 16-induced disease of claim 81, wherein the determined ratio is (E6+E7)/(L1+L2).

100. The method of diagnosing a stage of HPV 16-induced disease of claim 81, wherein the determined ratio is (E6+E7)/(L1+E2).

101. The method of diagnosing a stage of HPV 16-induced disease of claim 81, wherein the determined ratio is (E6+E7)/(L2+E2).

102. The method of diagnosing a stage of HPV 16-induced disease of claim 81, wherein the determined ratio is (E6+E7)/(L1+L2+E2).

103. A method of diagnosing HPV 16-induced cancer comprising the steps of:

quantifying a first level of one or more HPV 16 mRNAs from a sample collected from a patient infected with HPV, wherein the one or more HPV 16 mRNA is selected from the group consisting of E6 mRNA and E7 mRNA;

quantifying a second level of one or more HPV 16 mRNA from said patient, wherein the one or more mRNA is selected from the group consisting of E2 mRNA, E4 mRNA, L1 mRNA and L2 mRNA; and

determining a ratio of the quantified first and second levels of HPV 16 mRNA, wherein the ratio is selected from the group consisting of (E6+E7)/L1, (E6+E7)/(L1+L2), and (E6+E7)/(E2+E4),

wherein a ratio of greater than 4 is indicative of HPV 16-induced cancer.

104. The method of diagnosing HPV 16-induced cancer of claim 103, wherein the determined ratio is (E6+E7)/L1.

105. The method of diagnosing HPV 16-induced cancer of claim 103, wherein the determined ratio is (E6+E7)/(L1+L2).

106. The method of diagnosing HPV 16-induced cancer of claim 103, wherein the determined ratio is (E6+E7)/(E2+E4).

107. A method of diagnosing the risk or onset of HPV 16-induced cancer comprising the steps of:

quantifying a group 1 HPV 16 mRNA from a sample collected from a patient infected with HPV;

quantifying a group 2 HPV 16 mRNA from a sample collected from a patient infected with HPV; and

determining a ratio of group 1 mRNA level to group 2 mRNA level;

wherein any ratio of greater than 4 is indicative of high risk or onset of HPV 16-induced cancer.

108. A method of diagnosing the risk or onset of HPV 16-induced cancer comprising the steps of:

quantifying a group 1 HPV 16 mRNA from a sample collected from a patient infected with HPV;

quantifying a group 3 HPV 16 mRNA from a sample collected from a patient infected with HPV; and

determining a ratio of group 1 mRNA level to group 3 mRNA level;

wherein any ratio of greater than 4 is indicative of high risk or onset of HPV 16-induced cancer.