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Serum antibodies to the HPV16 proteome as biomarkers for head and neck cancer.

Anderson KS, Wong J, D'Souza G, Riemer AB, Lorch J, Haddad R, Pai SI, Longtine J, McClean M, LaBaer J, Kelsey KT, Posner M - Br. J. Cancer (2011)

Bottom Line: The ratios of specific median fluorescence intensity to p21-GST compared with controls were E1: 50.7 vs 2.1; E4: 14.6 vs 1.3; E6: 11.3 vs 2.4; E7: 43.1 vs 2.6; and L1: 10.3 vs 2.6 (each P≤0.01).In a validation cohort, HPV16 E1, E2, and E7 antibody levels were significantly elevated compared with healthy control samples (P≤0.02) and partners of OPC patients (P≤0.01).Patients with HPV16+ OPC have detectable Abs to E1, E2, and E7 proteins, which are potential biomarkers for HPV-associated OPC.

View Article: PubMed Central - PubMed

Affiliation: Cancer Vaccine Center, Dana-Farber Cancer Institute, Boston, MA 02115, USA. kanderson@partners.org

ABSTRACT

Background: Human papillomavirus (HPV) type 16 is associated with oropharyngeal carcinomas (OPC). Antibodies (Abs) to HPV16 E6 and E7 oncoproteins have been detected in patient sera; however, Abs to other early HPV-derived proteins have not been well explored.

Methods: Antibodies to the HPV16 proteome were quantified using a novel multiplexed bead assay, using C-terminal GST-fusion proteins captured onto Luminex beads. Sera were obtained from untreated patients with OPC (N=40), partners of patients with HPV16+ OPC (N=11), and healthy controls (N=50).

Results: Oropharyngeal carcinomas patients with known virus-like capsid particle+ Abs had elevated serum Abs to HPV16 E1, E2, E4, E6, and E7, and L1 antibody levels, but not E5. The ratios of specific median fluorescence intensity to p21-GST compared with controls were E1: 50.7 vs 2.1; E4: 14.6 vs 1.3; E6: 11.3 vs 2.4; E7: 43.1 vs 2.6; and L1: 10.3 vs 2.6 (each P≤0.01). In a validation cohort, HPV16 E1, E2, and E7 antibody levels were significantly elevated compared with healthy control samples (P≤0.02) and partners of OPC patients (P≤0.01).

Conclusion: Patients with HPV16+ OPC have detectable Abs to E1, E2, and E7 proteins, which are potential biomarkers for HPV-associated OPC.

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Related in: MedlinePlus

Specific detection of multiple early gene Abs in untreated OPC patients, but not partners. The MFI ratio of HPV16 proteins to p21 protein detected in sera is shown. The validation set serum IgG responses were measured in an independent set of healthy controls (‘Controls', N=30), OPC patients (‘Cases', N=30), and partners of OPC patients (N=11). HPV16-specific Abs to E1, E2, E4, E6, and E7, and L1 proteins are specifically detected in patients compared with controls.
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fig3: Specific detection of multiple early gene Abs in untreated OPC patients, but not partners. The MFI ratio of HPV16 proteins to p21 protein detected in sera is shown. The validation set serum IgG responses were measured in an independent set of healthy controls (‘Controls', N=30), OPC patients (‘Cases', N=30), and partners of OPC patients (N=11). HPV16-specific Abs to E1, E2, E4, E6, and E7, and L1 proteins are specifically detected in patients compared with controls.

Mentions: As the training set sera were specifically selected for head and neck cancer patients with L1-specific Abs, we evaluated OPC patients at DFCI and JHU with unknown serum HPV L1 status, compared with controls. The clinical characteristics of the OPC patients are shown in Table 3. Human papillomavirus type 16 E1, NE2, CE2, E4, E6, E7, and L1-specific Abs were significantly more common among OPC patient sera compared with healthy controls (E1, NE2, CE2, E4, E6, E7, and L1, each P<0.007) (Figure 3; Table 4). There was no specific detection of E5 or L2 Abs in cases. In this unselected cohort, the detection of L1-specific Abs was only 23% (7 out of 30) compared with healthy controls (1 out of 30, 3%).


Serum antibodies to the HPV16 proteome as biomarkers for head and neck cancer.

Anderson KS, Wong J, D'Souza G, Riemer AB, Lorch J, Haddad R, Pai SI, Longtine J, McClean M, LaBaer J, Kelsey KT, Posner M - Br. J. Cancer (2011)

Specific detection of multiple early gene Abs in untreated OPC patients, but not partners. The MFI ratio of HPV16 proteins to p21 protein detected in sera is shown. The validation set serum IgG responses were measured in an independent set of healthy controls (‘Controls', N=30), OPC patients (‘Cases', N=30), and partners of OPC patients (N=11). HPV16-specific Abs to E1, E2, E4, E6, and E7, and L1 proteins are specifically detected in patients compared with controls.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3111202&req=5

fig3: Specific detection of multiple early gene Abs in untreated OPC patients, but not partners. The MFI ratio of HPV16 proteins to p21 protein detected in sera is shown. The validation set serum IgG responses were measured in an independent set of healthy controls (‘Controls', N=30), OPC patients (‘Cases', N=30), and partners of OPC patients (N=11). HPV16-specific Abs to E1, E2, E4, E6, and E7, and L1 proteins are specifically detected in patients compared with controls.
Mentions: As the training set sera were specifically selected for head and neck cancer patients with L1-specific Abs, we evaluated OPC patients at DFCI and JHU with unknown serum HPV L1 status, compared with controls. The clinical characteristics of the OPC patients are shown in Table 3. Human papillomavirus type 16 E1, NE2, CE2, E4, E6, E7, and L1-specific Abs were significantly more common among OPC patient sera compared with healthy controls (E1, NE2, CE2, E4, E6, E7, and L1, each P<0.007) (Figure 3; Table 4). There was no specific detection of E5 or L2 Abs in cases. In this unselected cohort, the detection of L1-specific Abs was only 23% (7 out of 30) compared with healthy controls (1 out of 30, 3%).

Bottom Line: The ratios of specific median fluorescence intensity to p21-GST compared with controls were E1: 50.7 vs 2.1; E4: 14.6 vs 1.3; E6: 11.3 vs 2.4; E7: 43.1 vs 2.6; and L1: 10.3 vs 2.6 (each P≤0.01).In a validation cohort, HPV16 E1, E2, and E7 antibody levels were significantly elevated compared with healthy control samples (P≤0.02) and partners of OPC patients (P≤0.01).Patients with HPV16+ OPC have detectable Abs to E1, E2, and E7 proteins, which are potential biomarkers for HPV-associated OPC.

View Article: PubMed Central - PubMed

Affiliation: Cancer Vaccine Center, Dana-Farber Cancer Institute, Boston, MA 02115, USA. kanderson@partners.org

ABSTRACT

Background: Human papillomavirus (HPV) type 16 is associated with oropharyngeal carcinomas (OPC). Antibodies (Abs) to HPV16 E6 and E7 oncoproteins have been detected in patient sera; however, Abs to other early HPV-derived proteins have not been well explored.

Methods: Antibodies to the HPV16 proteome were quantified using a novel multiplexed bead assay, using C-terminal GST-fusion proteins captured onto Luminex beads. Sera were obtained from untreated patients with OPC (N=40), partners of patients with HPV16+ OPC (N=11), and healthy controls (N=50).

Results: Oropharyngeal carcinomas patients with known virus-like capsid particle+ Abs had elevated serum Abs to HPV16 E1, E2, E4, E6, and E7, and L1 antibody levels, but not E5. The ratios of specific median fluorescence intensity to p21-GST compared with controls were E1: 50.7 vs 2.1; E4: 14.6 vs 1.3; E6: 11.3 vs 2.4; E7: 43.1 vs 2.6; and L1: 10.3 vs 2.6 (each P≤0.01). In a validation cohort, HPV16 E1, E2, and E7 antibody levels were significantly elevated compared with healthy control samples (P≤0.02) and partners of OPC patients (P≤0.01).

Conclusion: Patients with HPV16+ OPC have detectable Abs to E1, E2, and E7 proteins, which are potential biomarkers for HPV-associated OPC.

Show MeSH
Related in: MedlinePlus