HUMAN PAPILLOMA VIRUS AS PREDICTOR OF CANCER PROGNOSIS

1 .- 29 . (canceled)

30 . A method of treating a subject with a cyclin dependent kinase (CDK) inhibitor, wherein the subject has a squamous cell carcinoma of the head and neck (HNSCC), and wherein the CDK inhibitor inhibits one or both of cyclin dependent kinase 4 (CDK4) or cyclin dependent kinase 6 (CDK6), the method comprising the steps of:

determining whether the subject has a mutation in a cell-cycle gene by:

obtaining a biological sample from the subject; and

performing an assay on the biological sample to determine if the subject has a mutation in a cell-cycle gene; and

if the subject has a mutation in a cell-cycle gene, then administering the CDK inhibitor to the subject.

31 . The method of claim 30 , wherein the cell-cycle gene is chosen from a cyclin dependent kinase inhibitor 2A (CDKN2A) gene, a cyclin dependent kinase inhibitor 2B (CDKN2B) gene, a Cyclin E1 (CCNE1) gene, a Cyclin D1 (CCND1) gene, a Cyclin D2 (CCND2) gene, a Cyclin D3 (CCND3) gene, a CDK4 gene, a CDK6 gene, or a gene described in Table 1 or Table 4.

32 . The method of claim 30 , wherein the subject has one or more of:

(i) a loss-of-function mutation in a CDKN2A gene;

(ii) a gain-of-function mutation in a CCND1 gene;

(iii) a mutation or a mutant polypeptide described in Table 1 or 4; or

(iv) a mutant CDKN2A, CDKN2B, or CCND1 polypeptide.

33 . The method of claim 30 , wherein the mutation in the cell-cycle gene is detected in a nucleic acid molecule by one or more of: sequencing, a nucleic acid hybridization assay, an amplification-based assay, a PCR-RFLP assay, real-time PCR, screening analysis, FISH, spectral karyotyping, MFISH, comparative genomic hybridization, in situ hybridization, SSP, HPLC, or mass-spectrometric genotyping.

34 . The method of claim 30 , wherein the CDK inhibitor is chosen from LEE011, LY-2835219, PD 0332991, Indisulam, AZD5438, SNS-032, SCH 727965, JNJ-7706621, indirubin, or Seliciclib.

35 . The method of claim 30 , further comprising administering a radiation therapy to the subject, performing a surgery on the subject, or both.

36 . The method of claim 30 , further comprising generating a personalized cancer treatment report to memorialize the presence or absence of a mutation in a cell-cycle gene in the subject.

37 . The method of claim 30 , wherein the biological sample is a blood sample, a serum sample, a urine sample, a tissue sample, or a buccal swab, or wherein the biological sample comprises a cell from a tumor biopsy or a circulating tumor cell.

38 . A method of treating a subject with a cyclin dependent kinase (CDK) inhibitor, wherein the subject has a squamous cell carcinoma of the head and neck (HNSCC), the method comprising the steps of:

determining whether the subject is negative for the human papillomavirus (HPV−) or positive for the human papillomavirus (HPV+) by:

obtaining a biological sample from the subject; and

performing an assay on the biological sample to determine if the subject is HPV− or HPV+; and

if the subject is HPV−, then administering the CDK inhibitor to the subject, and

if the subject is HPV+, then administering an anti-cancer agent other than a CDK inhibitor to the subject.

39 . The method of claim 38 , wherein the CDK inhibitor inhibits one or both of cyclin dependent kinase 4 (CDK4) or cyclin dependent kinase 6 (CDK6).

40 . The method of claim 38 , wherein the CDK inhibitor is chosen from LEE011, LY-2835219, PD 0332991, Indisulam, AZD5438, SNS-032, SCH 727965, JNJ-7706621, indirubin, or Seliciclib.

41 . The method of claim 38 , wherein the anti-cancer agent is chosen from 4-hydroxyperoxycyclophosphoramide, 5-fluorouracil (5-FU), 5-fluorodeoxyuridine (5-FUdR), 5-azacytidine, 6-mercaptopurine, 6-thioguanine, actinomycin D, amsacrine, bis-chloroethylnitrosurea, bleomycin, bryostatin-1, busulfan, carboplatin, chlorambucil, cisplatin, cetuximab, colchicine, cyclophosphamide, cytarabine, cytosine arabinoside, dacarbazine, daunorubicin, daunomycin, dactinomycin, deoxycoformycin, diethylstilbestrol (DES), doxorubicin, etoposide (VP-16), epirubicin, esorubicin, gemcitabine, hexamethylmelamine, hydroxyprogesterone, hydroxyurea, idarubicin, ifosfamide, irinotecan, mafosfamide, melphalan, methotrexate (MTX), methylcyclohexylnitrosurea, mithramycin, mitomycin C, mitoxantrone, nitrogen mustards, paclitaxel, pentamethylmelamine, prednisone, procarbazine, tamoxifen, taxol, teniposide, testosterone, trimetrexate, topotecan, vincristine, or vinblastine.

42 . The method of claim 38 , further comprising administering an mTOR inhibitor, a PI3K inhibitor, a PI3K/mTOR inhibitor, or a PI3K/Akt/mTOR inhibitor.

43 . The method of claim 42 , wherein the mTOR inhibitor is rapamycin, a rapamycin derivative, resveratrol, or everolimus.

44 . The method of claim 42 , wherein the PI3K/mTOR inhibitor is BEZ235, BGT226, BKM120, LY294002 or wortmannin.

45 . The method of claim 38 , further comprising administering a radiation therapy to the subject, performing a surgery on the subject, or both.

46 . The method of claim 38 , wherein the subject has one or more of:

(i) a loss-of-function mutation in a CDKN2A gene;

(ii) a gain-of-function mutation in a CCND1 gene;

(iii) a mutation or a mutant polypeptide described in Table 1 or 4; or

(iv) a mutant CDKN2A, CDKN2B, or CCND1 polypeptide.

47 . The method of claim 38 , wherein the subject has a mutation in a phosphoinositide-3-kinase, catalytic, alpha polypeptide (PIK3CA) gene; a phosphatase and tensin homolog (PTEN) gene; or a serine/threonine kinase 11 (STK11) gene.

48 . The method of claim 38 , wherein the biological sample is a blood sample, a serum sample, a urine sample, a tissue sample, or a buccal swab, or comprises a cell from a tumor biopsy or a circulating tumor cell.

49 . A method of treating a subject with a cyclin dependent kinase (CDK) inhibitor, wherein the subject has a squamous cell carcinoma of the head and neck (HNSCC), the method comprising the steps of:

determining whether the subject is positive for the human papillomavirus (HPV+) by:

obtaining a biological sample from the subject; and

performing an assay on the biological sample to determine if the subject is HPV+; and

if the subject is HPV+, then administering an mTOR inhibitor, a PI3K inhibitor, a PI3K/mTOR inhibitor, or a PI3K/Akt/mTOR inhibitor to the subject.

50 . The method of claim 49 , wherein the subject has a mutation in a phosphoinositide-3-kinase, catalytic, alpha polypeptide (PIK3CA) gene; a phosphatase and tensin homolog (PTEN) gene; or a serine/threonine kinase 11 (STK11) gene.

51 . The method of claim 49 , wherein the mTOR inhibitor is rapamycin, a rapamycin derivative, resveratrol, or everolimus.

52 . The method of claim 49 , wherein the PI3K/mTOR inhibitor is BEZ235, BGT226, BKM120, LY294002 or wortmannin.

53 . The method of claim 49 , further comprising administering a radiation therapy to the subject, performing a surgery on the subject, or both.

54 . The method of claim 49 , wherein the biological sample is a blood sample, a serum sample, a urine sample, a tissue sample, or a buccal swab, or comprises a cell from a tumor biopsy or a circulating tumor cell.