Table 2. Summary of the 12 polymorphisms found to have significantly changed in time during the last twenty years.

Residue position	p-value for trend		Position states		Sequence of known eptiopes	In our study			State that increases in time
	Subtype B	Subtype F	Consensus	Polimorphims		OR	Power	p-value
Inside known epitopes
P030	0.038	0.106	R	K	KW9-A24: KYKLKHIVW	0.23	0.83	0.0055	R
					GK9-B08: GGKKKYKLK	NC	0.42
P076	0.029	0.030	R	K	RY11-A30: RSLYNTVAVLY	1.70	0.08		K
					EV9-B08: EL R SLYNTV	1.25	0.05
P083	0.904	0.031	A	V	SL9-A02: SLYNTVATL	0.10	0.94	0.0008	A
					RY11-A30: RSLYNTVATLY	NC	<0.01
P084	0.012	0.730			SL9-A02: SLYNTVATL	0.34	0.77	0.0716	V
			V	T	RY11-A30: RSLYNTVATLY	1.79	0.13
					TI9-A11: TLYCVHQRI	2.83	0.30
P095	0.088	0.040	K	R	IL10-B40: IEIKDTKEAL	0.82	0.15		K
P215	0.031	0.930	L	V	EL9-B40: EEAAEWDR L	0.42	0.15		L
P218	0.047	0.770	V	A	AV9-B40: AEWDRLHP V	2.84	0.29		A
					HA9-B07: HPVHAGPIA	NPC	0.03
P223	0.123	0.009	I	V	HA9-B07: HPVHAGPIA	1.55	0.13		V
P280	0.601	0.020	V	T	RI8-B52: RMYSPTSI (1)	2.61	0.11		T
					VI9-Cw18: VRMYSPVSI (1)	NPC	NPC
Inside predicted epitopes
P090	0.614	0.028	Q	K R	AK9-A11: AVLYCVHQK				(2)
					CK9-A03: CVHKKIEVK
P054	0.555	0.009	S	A P T	EI9-B68: ETAEGCRQI (1)				(2)
P138	0.628	0.040	L	A F H I M P V	NL8-A24: NYPIVQN L				(2)

Detailed are the p-values obtained by Chi-squared test for trend. Note that except for position P76, the other positions have significantly changed only in one of either the B or F subtype. Aminoacidic sequences of known epitopes surrounding these mutations are shown, and highlighted in black-cursive the residue that changed. Enlarged are the anchor residues for binding to the HLA molecule. Statistical results for the pair position-HLAallele in our study are detailed. Note that we only have enough statistical power to detect association at positions P30, P83 and P84. (1) In these cases no information was available of anchor residues. (2) In these cases was observed a significant increase in time of all the residues alternatives to the consensus residue as a group. NPC: not possible to calculate.