Serum HPV16 E7 Oncoprotein Is a Recurrence Marker of Oropharyngeal Squamous Cell Carcinomas
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patient Samples
2.2. Nucleic Acid Extraction
2.3. HPV Analysis
2.4. Gene Expression Analysis
2.5. Detection of Serum HPV16 L1 Antibodies
2.6. Serum E7 Oncoprotein Level Detection
2.7. Statistical Analysis
3. Results
3.1. HPV DNA Analysis
3.2. p16 Gene Expression
3.3. HPV mRNA Expression
3.4. Serological Studies
3.4.1. HPV16 L1 Antibody Titer
3.4.2. HPV16 E7 Oncoproteins in Sera
3.5. Survival Analysis
3.5.1. RFS and OS in Correlation to HPV DNA, p16 Expression and HPV mRNA
3.5.2. RFS and OS in Relation to Serum HPV16 L1 Antibodies
3.5.3. RFS and OS in Relation to Serum HPV16 E7 Oncoprotein
3.6. TNM Stage in Correlation to OPSCC Patient Prognosis and E7 Oncoprotein in Serum
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Clinicopathological Variables | HPV-Negative | HPV-Positive | p-Value | Tumor Site (HPV-Positive) | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Oral | p-Value * | Oropharynx | p-Value | Hypopharynx | p-Value * | Larynx | p-Value * | ||||
Tumor Site | |||||||||||
Oral | 25/47 (53.20%) | 2/20 (10%) | |||||||||
Oropharynx | 13/47 (27.66%) | 15/20 (75%) | |||||||||
Hypopharynx | 1/47 (2.13%) | 2/20 (10%) | |||||||||
Larynx | 6/47 (12.77%) | 1/20 (5%) | |||||||||
Hidden 1 | 2/47 (4.25%) | - | |||||||||
Tumor Size | |||||||||||
T1 | 7/47 (14.89%) | 3/20 (15%) | 0.225 | - | NA | 2/15 (13.33%) | 0.031 | 1/2 (50%) | NA | - | NA |
T2 | 14/47 (29.79%) | 5/20 (25%) | - | 4/15 (26.67%) | 1/2 (50%) | - | |||||
T3 | 9/47 (19.15%) | 3/20 (15%) | - | 3/15 (20.00%) | - | - | |||||
T4 | 17/47 (36.17%) | 9/20 (45%) | 2/2 (100%) | 6/15 (40.00%) | - | 1/1 (100%) | |||||
Node Status | |||||||||||
N0 | 9/47 (19.15%) | 3/20 (15%) | 0.108 | - | NA | 2/15 (13.33%) | 0.096 | - | NA | 1/1 (100%) | NA |
N+ | 38/47 (80.85%) | 17/20 (85%) | 2/2 (100%) | 13/15 (86.67%) | 2/2 (100%) | - | |||||
Clinical Stage | |||||||||||
I | 1/47 (2.13%) | 1/20 (5%) | 0.467 | - | 1/15 (6.67%) | 0.336 | - | NA | - | NA | |
II | 7/47 (14.89%) | 5/20 (25%) | - | 5/15 (33.33%) | - | - | |||||
III | 7/47 (14.89%) | 5/20 (25%) | - | 4/15 (26.67%) | 1/2 (50%) | - | |||||
IVa | 25/47 (53.19%) | 9/20 (45%) | 2/2 (100%) | 5/15 (33.33%) | 1/2 (50%) | 1/1 (100%) | |||||
Ivb/c | 7/47 (14.89%) | - | - | - | - | - | |||||
Recurrence | 16/47 (42.55%) | 6/20 (30%) | 0.0001 | 1/2 (50%) | NA | 4/15 (26.66%) | 0.001 | 1/2 (50%) | NA | 0/1 (0%) | NA |
Persistance | 4/47 (8.51%) | 2/20 (10%) | 2/15 (13.33%) | ||||||||
N/A | 2/47 (4.25%) | 2/20 (10%) | - | 2/15 (13.33%) | - | - | |||||
Tobacco consumption | |||||||||||
No | 5/47 (10.64%) | 2/20 (10%) | 0.481 | - | NA | 2/15 (13.33%) | 0.582 | - | NA | - | NA |
Ex Smoker | 13/47 (27.66%) | 7/20 (35%) | - | 4/15 (26.67%) | 2/2 (100%) | 1/1 (100%) | |||||
Smoker | 25/47 (53.19%) | 7/20 (35%) | 2/2 (100%) | 5/15 (33.33%) | - | - | |||||
N/A | 4/47 (8.51%) | 4/20 (20%) | - | 4/15 (26.67%) | - | - | |||||
Alcohol consumption | |||||||||||
No | 10/47 (21.28%) | 5/20 (25%) | 0.962 | - | NA | 4/15 (26.67%) | 0.725 | - | NA | 1/1 (100%) | NA |
Ex consumer | 3/47 (6.38%) | 2/20 (10%) | 1/2 (50%) | 0/15 (0%) | 1/2 (50%) | - | |||||
Consumer | 27/47 (57.45%) | 9/20 (45%) | 1/2 (50%) | 7/15 (46.67%) | 1/2 (50%) | - | |||||
N/A | 7/47 (14.89%) | 4/20 (20%) | - | 4/15 (26.67%) | - | - | |||||
Age | 64.04 ± 11.55 | 67,05 ± 9,05 | 0.709 | 63 ± 1.41 | NA | 65.73 ± 9.15 | 0.409 | 73 ± 1.41 | NA | 83 ± NA | NA |
Gender | |||||||||||
Male | 32/47 (68.09%) | 17/20 (85%) | 0.244 | 2/2 (100%) | NA | 12/15 (80%) | 0.289 | 2/2 (100%) | NA | 1/1 (100%) | NA |
Female | 15/47 (31.91%) | 3/20 (15%) | - | 3/15 (20%) | - | - |
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Oton-Gonzalez, L.; Rotondo, J.C.; Lanzillotti, C.; Mazzoni, E.; Bononi, I.; Iaquinta, M.R.; Cerritelli, L.; Malagutti, N.; Ciorba, A.; Bianchini, C.; et al. Serum HPV16 E7 Oncoprotein Is a Recurrence Marker of Oropharyngeal Squamous Cell Carcinomas. Cancers 2021, 13, 3370. https://doi.org/10.3390/cancers13133370
Oton-Gonzalez L, Rotondo JC, Lanzillotti C, Mazzoni E, Bononi I, Iaquinta MR, Cerritelli L, Malagutti N, Ciorba A, Bianchini C, et al. Serum HPV16 E7 Oncoprotein Is a Recurrence Marker of Oropharyngeal Squamous Cell Carcinomas. Cancers. 2021; 13(13):3370. https://doi.org/10.3390/cancers13133370
Chicago/Turabian StyleOton-Gonzalez, Lucia, John Charles Rotondo, Carmen Lanzillotti, Elisa Mazzoni, Ilaria Bononi, Maria Rosa Iaquinta, Luca Cerritelli, Nicola Malagutti, Andrea Ciorba, Chiara Bianchini, and et al. 2021. "Serum HPV16 E7 Oncoprotein Is a Recurrence Marker of Oropharyngeal Squamous Cell Carcinomas" Cancers 13, no. 13: 3370. https://doi.org/10.3390/cancers13133370