Background Evidence on salvage resection for localised ASCC after chemoradiotherapy (CRT) are often based on institutional case cohort studies with the biggest predictor of survival based on margin status. The impact of the biomarker p16 is unknown. The objective of this study is to examine prognostic factors associated with survival outcome after salvage surgery for relapsed ASCC. Methods Patients who underwent salvage surgery after radical CRT for ASCC were consecutively analysed at Peter MacCallum. Primary end points included OS, LRFS and DMFS. Survival analyses were estimated using the Kaplan Meir method. Cox Proportional Hazards Model was used to assess for independent prognostic factors. Results Overall, our study identified 73 patients who underwent curative salvage surgery for ASCC. The 5-year OS, LRFS and DMFS were 52%, 56% and 56% respectively, over a median follow up of 49 months. Median OS was 63 months. 39% of patients had local relapse after salvage surgery. Univariate analyses identified p16 negative status (HR 3.24, CI 1.04-10.11, p<0.05), positive margins (R+) (HR6.34, CI 2.99-13.63, p<0.001) and nodal positivity in the resection specimen (HR 4.75, CI 1.53-14.7, p<0.01) to be associated with worse OS. R+ was prognostic for inferior OS and LRFS on multivariate regression. p16 negative phenotype fared significantly worse in OS (Median OS: 13.7 months vs 76.7 months, HR 3.88, CI 0.63-24.04, p<0.01) and LRFS (Median LRFS: 8.5 months vs not reached, HR 3.48, CI 0.62- 19.65, p<0.05) utilising Log Rank comparison. Conclusion Our study has identified pathological risk features including p16 negative, nodal positivity and margin status in predicting outcomes of ASCC patients undergoing salvage surgery.