Human papillomavirus in upper digestive tract tumors from three countries

Table 1 Sex and age distribution of oral carcinoma and esophageal cancer cases

	Cancer site
	Oral	Esophagus
Male/total (%)
Japan	11/17 (65)	66/75 (88)
Pakistan	30/48 (63)	25/42 (59)
Colombia	4/6 (67)	27/49 (55)
1P value	0.972	< 0.001
Mean age in yr (95% confidence interval )
Japan	68 (64, 73)	64 (62, 65)
Pakistan	49 (45, 53)	54 (50, 57)
Colombia	67 (61, 73)	64 (60, 67)
2P value	0.013	< 0.001

¹P values were obtained by χ² test.

²P values were obtained by one-way analysis of variance.

Table 2 Frequency of human papillomavirus DNA in tumors by cancer site and country n (%)

Cancer site country	Total	HPV-positive	HPV16-positive	Multiple HPV
Oral cavity	71	40 (56)	39 (55)	0
Japan	17	8 (47)	7 (41)	0
Pakistan	48	27 (56)	27 (56)	0
Colombia	6	5 (83)	5 (83)	0
1P value		0.305	0.193	-
Esophageal	166	31 (19)	24 (14)	13 (8)
Japan	75	11 (15)	9 (12)	5 (7)
Pakistan	42	11 (26)	9 (21)	5 (12)
Colombia	49	9 (18)	6 (12)	3 (6)
1P value		0.308	0.331	0.521

¹Comparison among the three countries by χ² test. HPV: Human papillomavirus.

Table 3 List of esophageal carcinomas with human papillomavirus genome other than human papillomavirus 16

Country	Sex	Age (yr)	HPV16	Other HPV type
Japan	Male	49	-	6
	Male	66	-	51/68
	Female	64	+	18
	Male	67	+	51
	Female	75	+	51
	Male	65	+	51
Pakistan	Female	39	-	18
	Male	43	-	45
	Male	48	+	6
	Male	34	+	6
	Male	54	+	35
	Male	55	+	45
	Male	58	+	45
Colombia	Male	59	-	18
	Male	65	-	18
	Female	68	-	18
	Female	74	+	6
	Female	72	+	18
	Male	67	+	18

HPV: Human papillomavirus.

Table 4 Physical status and E6 variants of human papillomavirus16 in Japan, Pakistan and Colombia

		n (%)
		All	Japan	Pakistan	Colombia	1P value
Oral cavity		39	7	27	5
Physical status	Episomal	2	0	2 (7)	0	0.147
	Mixed	3	0	1 (4)	2 (40)
	Integrated	34	7 (100)	24 (89)	3 (60)
HPV16 E6 variant	Prototype	6	3 (75)	3 (21)	0	0.048
	E-350G	13	1 (25)	9 (64)	3 (60)
	Asian	2	0	2 (14)	0
	Asian-American	2	0	0	2 (40)
Esophagus		24	9	9	6
Physical status	Episomal	2	0	0	2 (33)	0.017
	Mixed	5	0	4 (44)	1 (17)
	Integrated	17	9 (100)	5 (56)	3 (50)
HPV16 E6 variant	Prototype	2	2 (40)	0	0	< 0.001
	E-350G	8	3 (60)	5 (100)	0
	Asian	0	0	0	0
	Asian-American	6	0	0	6 (100)

¹P values were obtained by Fisher’s exact test. HPV: Human papillomavirus.

Table 5 Viral load of human papillomavirus 16 by country, physical status, and human papillomavirus 16 E6 variants

		n	Viral load/cell
			GM	95% CI	1P value
Oral cavity	All	39	0.064	0.022, 0.185
Country	Japan	7	0.047	0.028, 0.079	0.033
	Pakistan	27	0.037	0.010, 0.144
	Colombia	5	1.883	0.058, 61.21
Integrated form	Absent	2	0.001	-	0.048
	Present	37	0.081	0.028, 0.233
E6 variant	E-350G	13	1.081	0.249, 4.705	0.038
	Others	10	0.127	0.063, 0.256
Esophagus	All	24	0.121	0.053, 0.274
Country	Japan	9	0.072	0.023, 0.222	0.476
	Pakistan	9	0.124	0.019, 0.799
	Colombia	6	0.251	0.036, 1.737
Integrated form	Absent	2	0.161	-	0.601
	Present	22	0.118	0.049, 0.285
E6 variant	E-350G	8	0.444	0.101, 1.957	0.291
	Others	8	0.215	0.055, 0.847

¹P values were obtained by Kruskal-Wallis test or Mann-Whitney U test. CI: Confidence interval; GM: Geometric means.

Table 6 Clinicopathological features of oral and esophageal carcinomas n (%)

Cancer site	Pathological features	HPV-negative	HPV-positive	1P value
Oral cavity	2Histological grading
	Well-differentiated	17 (81)	20 (77)	0.899
	Moderate differentiation	3 (14)	5 (19)
	Poor differentiation	1 (5)	1 (4)
	3p53
	Positive	13 (45)	16 (48)	0.773
	Negative	16 (55)	17 (52)
	4p16INK4a
	Positive	11 (38)	10 (29)	0.427
	Negative	18 (62)	25 (71)
Esophagus	2Histological grading
	Well-differentiated	42 (31)	10 (32)	0.831
	Moderate differentiation	64 (48)	16 (52)
	Poor differentiation	28 (21)	5 (16)
	3p53
	Positive	59 (44)	11 (35)	0.368
	Negative	74 (56)	20 (65)
	4p16INK4a
	Positive	42 (33)	16 (53)	0.036
	Negative	86 (67)	14 (47)

¹P values were obtained by χ² test.

²Information of histological grading was missing for 10 human papillomavirus (HPV)-negative and 14 HPV-positive oral carcinomas (OCs), and two HPV-negative esophageal carcinomas (ECs). ³Tissue specimens were not enough to examine p53 expression in two HPV-negative and seven HPV-positive OCs, and two HPV-negative ECs. ⁴Tissue specimens were not enough to examine p16^INK4a expression in two HPV-negative and five HPV-positive OCs, and seven HPV-negative and one HPV-positive ECs.

Table 7 Detection of human papillomavirus genome in adjacent normal epithelium of human papillomavirus 16-positive Japanese esophageal carcinomas

Case ID/sex/age	ID # of block	Histology	HPV	HPV type
EC4/M/48	39	SCC	+	16
	132	SCC	-
	140	SCC	+	16
	14	Normal	-
	37	Normal	-
EC5/M/67	20	SCC	+	16, 51
	18	SCC	+	16
	114	SCC	+	6
	115	SCC	-
	41	Normal	+	6
EC7/F/75	35	SCC	+	16, 51
	15	SCC	-
	113	SCC	-
	24	Normal	+	6
EC10/M/66	12	SCC	+	16
	16	SCC	-
	20	Normal	-
	22	Normal	-
EC11/F/47	26	SCC	+	16
	118	SCC	-
	110	SCC	+	6
	41	Normal	-
EC16/M/65	55	SCC	+	16, 51
	55	Normal	+	6
EC28/M/61	12	SCC	+	16
	20	Normal	-
EC35/F/64	25	SCC	+	16, 18
	28	Normal	-
	33	Normal	-
EC61/M/64	12	SCC	+	16
	28	Normal	-
EC63/M/66	9	SCC	+	51, 68
	3	Dysplasia	-
	11	Normal	-
EC67/M/49	16	SCC	+	6
	15	SCC	-
	1	Normal	-

¹Additional esophageal carcinoma specimens analyzed for each patient. ID: Identification; SCC: Squamous cell carcinoma; EC: Esophageal carcinomal; HPV: Human papillomavirus.