Tumor HPV Status, Level of Regulatory T Cells and Macrophage Infiltration Predict up to 20-Year Non-Disease-Specific Survival in Oropharynx Squamous Cell Carcinoma Patients
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients Included in the Study
2.2. Immunohistochemistry
2.3. Scoring of IHC
2.4. Histological Evaluation
2.5. DNA Isolation
2.6. HPV DNA Detection
2.7. Calculating Standard Mortality
2.8. Statistics
3. Results
3.1. Clinical Parameters Sorted by Tumor HPV Presence, Age of Patient at Diagnosis, Tumor Site and TNM Stage
3.2. Twenty-Year Survival Dependent on Tumor HPV Status
3.3. Twenty-Year Survival by Kaplan–Meier Analyses, Studying TIL CD3, FoxP3 or TIM CD68 Positivity
3.4. Twenty-Year Survival by Kaplan–Meier Analyses Studying Tumor Cell Fraction of Mature Cells (Nuclear Polymorphism), Pattern of Invasion, Tumor Stromal Desmoplasia and Tumor Host Inflammatory Response
3.5. Twenty-Year Survival by Cox Multivariate Regression Analyses by TIL FoxP3, TIL CD3 and TIM CD68, Whether HE-Histology Generated Levels of Tumor Desmoplasia, Inflammation, Nuclear Ploidity, Invasion, Age of the Patient and T Stage, and Whether HPV Tumor Positivity
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Tumor HPV(−) | Tumor HPV(+) | |||
---|---|---|---|---|
Sign. 20 Y OS | Sign. 20 Y OS | |||
Age | n.s. | <0.001 | ||
Years Mean ± SD | 62.1 ± 11.0 | 58.6 ± 10.5 | ||
Gender (N) | n.s. | n.s. | ||
Males | 63 | 65 | ||
Females | 13 | 27 | ||
T stage | 0.042 | n.s. | ||
1 | 12 | 14 | ||
2 | 20 | 31 | ||
3 | 24 | 31 | ||
4 | 18 | 16 | ||
N stage | 0.016 | n.s. | ||
0 | 29 | 18 | ||
1 | 14 | 4 | ||
2 | 25 | 65 | ||
3 | 5 | 5 | ||
M stage | 0.001 | n.a. | ||
0 | 68 | 92 | ||
1 | 3 | 0 | ||
Smoking | n.s. | 0.064 | ||
0 | 3 | 11 | ||
1 | 1 | 10 | ||
2 | 2 | 12 | ||
3 | 15 | 29 | ||
4 | 48 | 26 | ||
Total patients included | 76 | 92 |
Patients | Number of Patients | Number of Deaths | Expected Deaths | RR | Confidence Interval |
---|---|---|---|---|---|
From diagnosis | |||||
All | 168 | 133 | 21 | 6.2 | 5.2–7.4 |
HPV(+) | 91 | 56 | 14 | 4.1 | 3.2–5.3 |
HPV(−) | 75 | 75 | 8 | 9.8 | 7.8–12.3 |
Patients with survival more than 5 years following diagnosis | |||||
All | 84 | 49 | 19 | 2.6 | 2.0–3.5 |
HPV(+) | 59 | 24 | 12 | 1.9 | 1.3–2.9 |
HPV(−) | 23 | 23 | 6 | 3.8 | 2.5–5.7 |
HPV(+) Non-smokers | 7 | 2 | 1.3 | 1.5 | 0.4–6.2 |
20-Year OS | 20-Year DSS Only | |||||||
---|---|---|---|---|---|---|---|---|
Sign. | RR | 95% CI for RR | Sign. | RR | 95% CI for RR | |||
Lower | Upper | Lower | Upper | |||||
Block I | ||||||||
Gender | 0.531 | 0.843 | 0.494 | 1.438 | 0.651 | 0.857 | 0.441 | 1.668 |
Age of patient | 0.000 | 1.06 | 1.035 | 1.083 | 0.000 | 1.077 | 1.041 | 1.113 |
T-stage | 0.073 | 1.20 | 0.983 | 1.471 | 0.234 | 1.194 | 0.892 | 1.599 |
N-stage | 0.006 | 1.36 | 1.095 | 1.698 | 0.289 | 1.174 | 0.873 | 1.578 |
M-stage | 0.016 | 7.18 | 1.437 | 35.832 | ||||
HPV | 0.000 | 0.37 | 0.235 | 0.588 | 0.002 | 0.364 | 0.193 | 0.686 |
Tobacco history | 0.002 | 1.35 | 1.114 | 1.625 | 0.007 | 1.432 | 1.105 | 1.856 |
Block I plus levels of TIL CD3 | ||||||||
TIL CD3 | 0.039 | 0.651 | 0.433 | 0.978 | 0.028 | 0.420 | 0.194 | 0.912 |
Block I plus levels of TIM CD68 | ||||||||
TIM CD68 | 0.011 | 0.573 | 0.373 | 0.881 | 0.005 | 0.698 | 0.545 | 0.895 |
Block I plus levels of TIL Foxp3 | ||||||||
TIL Foxp3 | 0.008 | 0.556 | 0.360 | 0.857 | 0.017 | 0.694 | 0.514 | 0.936 |
Block I plus level of desmoplasia | ||||||||
Desmoplasia | 0.084 | 1.202 | 0.976 | 1.480 | 0.408 | 1.295 | 0.702 | 2.391 |
Block I plus inflammation | ||||||||
Inflammation | 0.060 | 1.268 | 0.990 | 1.624 | 0.856 | 1.060 | 0.565 | 1.991 |
Block I plus level of nuclear polymorphism | ||||||||
Nuclear polymorphism | 0.950 | 1.009 | 0.764 | 1.333 | 0.363 | 0.722 | 0.358 | 1.457 |
Block I plus level of inflammation | ||||||||
Invasion | 0.484 | 1.091 | 0.855 | 1.391 | 0.603 | 0.853 | 0.469 | 1.552 |
RR: Relative risk. | ||||||||
CI: Confidence interval. | ||||||||
Abbreviations otherwise as in Table 1 and Table 2. |
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Haave, H.; Ljokjel, B.; Lybak, H.; Moe, S.E.; Berge, J.E.; Vintermyr, O.K.; Helgeland, L.; Aarstad, H.J. Tumor HPV Status, Level of Regulatory T Cells and Macrophage Infiltration Predict up to 20-Year Non-Disease-Specific Survival in Oropharynx Squamous Cell Carcinoma Patients. Biomedicines 2022, 10, 2484. https://doi.org/10.3390/biomedicines10102484
Haave H, Ljokjel B, Lybak H, Moe SE, Berge JE, Vintermyr OK, Helgeland L, Aarstad HJ. Tumor HPV Status, Level of Regulatory T Cells and Macrophage Infiltration Predict up to 20-Year Non-Disease-Specific Survival in Oropharynx Squamous Cell Carcinoma Patients. Biomedicines. 2022; 10(10):2484. https://doi.org/10.3390/biomedicines10102484
Chicago/Turabian StyleHaave, Hilde, Borghild Ljokjel, Helene Lybak, Svein E. Moe, Jan E. Berge, Olav K. Vintermyr, Lars Helgeland, and Hans J. Aarstad. 2022. "Tumor HPV Status, Level of Regulatory T Cells and Macrophage Infiltration Predict up to 20-Year Non-Disease-Specific Survival in Oropharynx Squamous Cell Carcinoma Patients" Biomedicines 10, no. 10: 2484. https://doi.org/10.3390/biomedicines10102484