Table 4. Summary of studies assessing the prognostic value of p16 in OTSCC providing unadjusted or adjusted estimates of HR and their 95% CIs for one or more endpoints, the HRs contrasting negative to positive expression.
| (Authors, year) Country | Stage or tumour size (primary treatment) | Primary antibody | Cutoff point in percentage | No. of cases | No. of positive cases (%) | Endpoint | Unadjusted analysis | Adjusted analysis | Compliance to REMARK guidelines |
|---|---|---|---|---|---|---|---|---|---|
| (Bova et al, 1999) Australia | T1–T4 (S only in 96 patients. S with adjuvant RT in 52 patients) | p16INK4A, clone ZJ11 (1 : 60; Neomarkers, Fremont, CA) | 1 | 147 | 65 (45.5) | OS | HR 2.50 (95% CI 1.16–5.41), P=0.02 | HR 2.32 (95% CI 1.04–5.16), P=0.04 | Fulfilled items summarised in Table 1 |
| DFS | HR 2.73 (95% CI 1.32–5.67), P=0.007 | HR 3.23 (95% CI 1.49–6.99), P=0.003 | |||||||
| (Goto et al, 2005) Japan | I–IV (S) | p16INK4A, clone E6H4 (dilution 1 : 25, Dako, Glostrup, Denmark) | 10 | 123 | 42 (34.1) | OS | HR 1.41 (95% CI 0.48–4.093), P=0.52 | NA | Checklist no. 5 was not fulfilled |
| DSS | HR 1.30 (95% CI 0.37–4.47), P=0.67 | NA | |||||||
| DFS | HR 1.84 (95%CI 0.78–4.33), P=0.15 | NA | |||||||
| (Trivedi et al, 2011) India | T1–T4 (S followed by RT in 26 cases, CT in 1 case, RT with CT in 5 cases) | p16, Monoclonal, clone SC-166 (1 : 150; Santa Cruz Biotechnology, USA) | 10 | 61 | 28 (46) | OS | HR 1.59 (95% CI 0.59–4.24), P=0.354 | NA | Checklist no. 1 and 5 were not fulfilled |
| RFS | HR 1.47 (95% CI 0.62–3.49), P=0.372 | NA | |||||||
| (Harris et al, 2011) USA | 40% were T1 (S in 23 cases, Radio-chemotherapy in 2 cases) | p16INK4A, monoclonal, MAB4133 (Chemicon International Company, Temecula, CA) | High= diffuse and intense staining. Low=no, weak and moderate staining | 25 | 11 (44) | OS | HRa 3.57 (95% CI 1–12.5) | NA | Checklist no. 1 and 5 were not fulfilled |
| RFS | HRa 4.35, (95% CI 1.35–14.3) | NA | |||||||
| (Ramshankar et al, 2014) India | I–II (S or brachytherapy) | p16, monoclonal, clone—JC8-sc-56330 (1 : 150; Santa Cruz Biotechnology Santa Cruz, CA, USA) | 50 | 156 | 24 (15.4) | OS | HRa 0.32 (95% CI 0.11–0.98) | HRa 0.42 (95% CI 0.23–0.77) | Fulfilled items summarised in Table 1 |
| DFS | HRa 0.212 (95% CI 0.07–0.66) | HRa 0.387 (95% CI 0.22–0.69) | |||||||
| (Lim et al, 2014) Australia | I–IV (S, S with adjuvant RT, S with adjuvant CT, CT or RT alone) | p16, monoclonal, E6H4; (Cintec/Roche) | 70 | 116 | 6 (5) | OS | HR 1.81 (95% CI: 0.44–7.47), P=0.40 | NA | Checklist 5 was not fulfilled |
| PFS | HR 1.14 (95% CI: 0.45–2.87), P=0.78 | NA |
Abbreviations: CI=confidence interval; CT=chemotherapy; DFS=disease-free survival; DSS=disease-specific survival; HR=hazard ratio; NA=not available; OS=overall survival; PFS= progression free survival; RFS=relapse-free survival; RT=radiotherapy; S=surgery.
a
HR in Harris et al study and Ramshankar et al study has been calculated by contrasting positive p16 vs negative p16, and we have converted it (as 1 divided by the reported HR and 1 divided by the reported CI) to be similar to all other studies in which HR was calculated by contrasting negative p16 vs positive p16.