Table 1. A summary of reported associations between p16 (immunohistochemistry) and HPV status (using PCR), and outcome from anal squamous cell carcinoma treated with chemoradiotherapy.

					Correlation with outcomec
	Patients; n (% M:F)a	Median follow-up (months)	Marker	% High riskb	Survival	Recurrence	Locoregional failure	Systemic failure
Yhim et al (2011)	47 (47 : 53)	51.7	HPV16	66.0 (31/47)	4 year OS rate: P=0.008. 84.6% vs 39.8%	4-year PFS rate: P<0.001. 63.1% vs 15.6%	4-year TTLF rate: P=0.006. 76.3% vs 36.8%	4-year TTSF rate: NS
			p16	83.0 (39/47)	NS	4-year PFS: P=0.014. 52.5% vs 25.0%	4-year TTLF: P=0.018. 69.3% vs 42.9%	4-year TTSF rate: NS
dGilbert et al (2013)	153 (39 : 61)	27.9	p16	89.5 (137/153)	N/A	Relapse rate: P = 0.0076. 27.0% vs 62.5%	N/A	N/A
Ravenda et al (2014)	50 (26 : 74)	48.0	HPV	84.0 (42/50)	5 year OS: NS	5-year PFS: P < 0.01. 92.5 vs 50.0%	N/A	N/A
Koerber et al (2014)	90 (14 : 86)	48.6	HPV	83.3 (75/90)	OS rate: P=0.007. 75.8% vs 48.0%	PFS: P < 0.001. 63.5% vs 26.7%	3-year local control rate: NS	Risk of distant recurrence: P=0.005
			p16	83.3 (75/90)	OS rate: NS	PFS: P<0.0017. 62.3% vs 33.3%	N/A	N/A
			HPV p16	77.8 (70/90)	OS rate: P=0.005. 77.1% vs 51.4%	PFS: P < 0.001. 64.0% vs 35.0%	3-year local control rate: P=0.023; 81.0% vs 55.9%	N/A
eRoldán Urgoiti et al (2014)	53 (25 : 75)	59.0	p16	80 (28/35)	5-year OS: P=0.01. HR 4.5 (95% CI 1.4–15)	5-year PFS: P = 0.006. HR 8.4 [95% CI 1.8–38.6]	Very high AQUA score (>244) associated with higher incidence of local or distant recurrence (P = 0.004)
Serup-Hansen et al (2014)	143 (26 : 74)	51.2	HPV	87.6 (120/137)	5-year OS: P = 0.036. 74% vs 52%	N/A	N/A	N/A
			p16	92.9 (131/141)	5-year OS: P < 0.001. 76% vs 30%	N/A	N/A	N/A
Rodel et al (2015)	95 (43 : 57)	40.0	HPV16	95.8 (91/95)	10-year OS: P = 0.020. HR 2.86 (95% CI 1.1–7.1)	N/A	Local failure rate: P = 0.023.	NS
			p16	65.2 (62/95)	NS	N/A	Local failure rate: P = 0.021.	NS
			HPV16 p16	U	10-year OS: P = 0.031.	N/A	Local failure rate: P = 0.019.	N/A
Meulendijks et al (2015)	107 (47 : 53)	30.0	HPV	87.0 (93/107)	3-year OS: P <0.001. 87% vs 35%	N/A	3-year TTLF rate: P < 0.001. 82% vs 15%	NS
			p16	91.0 (97/107)	NS	N/A	3-year TTLF rate: P<0.078. 75% vs 15%	NS
dBaricevic et al (2015)	110 (43 : 57)	28.0	HPV16	85.0 (93/110)	5-year OS: P = 0.019. 59% vs 38%	5-year RFS: P=0.027. 62% vs 40%	N/A	N/A
			p16	89.0 (98/110)	5-year OS: P < 0.001. 63% vs 13%	5-year RFS: P<0.001. 65% vs 16%	N/A	N/A
Mai et al (2015)	106 (41 : 59)	48.0 (LC) 54.0 (OS)	HPV p16	59.0 (63/106)	5-year OS: P = 0.011. 81.1% vs 68.8%	N/A	5-year LC: P = 0.002. 88.1% vs 55.8%	N/A

Abbreviations: HR, hazard ratio; HPV, human papilloma viruses; NA, not available/reported; NS, not significant; OS, overall survival; PFS, progression free survival; TTLF, time to locoregional failure; TTSF, time to systemic failure

Outcomes from univariate analyses are shown. Key: OS – time from the date of diagnosis to the date of death from any cause; PFS – time from the date of diagnosis/first day of treatment to the first documented date of progression; TTLF – time from the first day of treatment to the first documented date of disease progression; TTSF – time from the first day of treatment to the first documented distant metastasis. HR, provided here when univariate comparisons not available from text.

^aStatistically significant comparisons shown. All positive vs negative unless otherwise stated.

^bSubjects for whom biomarker positivity could be assessed.

^c‘High risk' deemed as high p16 expression and either the detection, or high levels of, HPV DNA.

^dOverlapping cohort of patients.

^eData relate to patients with a pre-treatment haemoglobin of 120 g l⁻¹. Lower pre-treatment haemoglobin was identified as an independent prognostic factor for poorer OS and PFS.