Association Of HPV Infection And The Risk And Prognosis Of Head And Neck Squamous Cell Carcinoma

Background:Molecular evidence suggests that human papillomavirus(HPV)has a role in the etiology of oropharyngeal squamous cell carcinoma.However,the role of HPV in laryngeal squamous cell carcinoma(LSCC)is unclear.Patients and methods:We conducted a case-control study using tumor tissue specimens from 300 LSCC patients and vocal cord polyp specimens from 300 cancer-free controls.HPV genotype,HPV 16 viral load and viral integration status,and p16 expression were determined.Results:The prevalence of HPV(all types)was higher in cases than controls[21(7.0%)versus 10(3.3%),adjusted odds ratio(aOR)2.37,95%CI 1.08-5.21].The prevalence of HPV 16 was higher in cases than controls[20(6.7%)versus 8(2.7%),aOR 2.84,95%CI 1.21-6.68].The risk of LSCC associated with HPV16 DNA positivity was even higher in patients aged 55 years or younger(aOR 3.52,95%CI 1.07-11.54),males(aOR 4.74,95%CI 1.33-16.90),never-smokers(aOR 5.57,95%CI 1.41-22.10),and never-drinkers(aOR 3.72,95%CI 1.09-12.72).HPV DNA was partly or fully integrated in all 20 HPV 16-positive cases but was episomal in all 8 HPV 16-positive controls;however,the HPV 16-positive cases and controls had similar viral loads(P=0.28).P16 immunostaining was positive in 31 of the 300 cases(10.3%)and negative in all 300 controls.All of the cases with HPV 16 infection except were positive for P16 immunostaining.Conclusion:These results suggest that prior infection with HPV 16 may play a role in the etiology of some LSCC.This larger case-control study will offer for the first time the possibility to address in depth the understanding of a tissue-specific role of HPV in laryngeal carcinogenesis.Further studies with larger samples are needed to confirm these findings.Objective:To investigate the association of PD-1 and PD-L1 expression and CD8+TILs infiltration,and HPV infection status and patient prognosis in oropharyngeal squamous cell carcinoma(OPSCC).Methods:The propensity score matching was used to include 50 cases of both HPV-positive and HPV-negative OPSCC.We assessed CD8+TILs infiltration,PD-1 and PD-L1 expression using immunofluorescence and the correlation with HPV infection and clinical prognosis wasanalyzed.Results:HPV-positive OPSCC had better prognosis compared to HPV-negative patients[overall survival(OS),p=0.002;disease specific survival(DSS),p=0.001].The 5-year OS rate were 66%and 40%,respectively.And the 5-year DSS rate were 73%and 44%,respectively.The infiltration of CD8+TILs and the expression of PD-1 and PD-L1 were significantly higher in the HPV-positive OPSCC than in the HPV-negative group(p=0.039;p=0.044;p=0.005).High CD8+TILs infiltration(aHR=0.38,95%CI 0.20-0.73,p=0.003)and PD-L1 positivity(aHR=0.43,95%CI 0.22-0.82,p=0.008)were independent prognostic factor for improved OS,similar results were obtained for the DSS.Further analysis showed HPV+/CD8+TILshigh patients had significantly better prognosis compared to HPV+/CD8+TILslow(DSS,P<0.001;OS,P<0.001),HPV-/CD8+TILshigh(DSS,P=0.009;OS,P=0.028)and HPV-/CD8+TILslow(DSS,P<0.001;OS,P<0.001).Similarly,HPV+/PD-L1+patients had significantly better prognosis compared to HPV+/PD-L1-(DSS,P<0.001;OS,P=0.004),HPV-/PD-L1+(DSS,P=0.009;OS,P=0.039)and HPV-/PD-L1-(DSS,P<0.001;OS,P<0.001).Conclusions:HPV-positive OPSCC had a significantly better prognosis.CD8+TILs infiltration and PD-L1 expression were elevated in HPV-positive OPSCC.High CD8+TILs infiltration and PD-L1 positivity may be related to the better prognosis of HPV-positive OPSCC.