Complex Etiology Underlies Risk and Survival in Head and Neck Cancer Human Papillomavirus, Tobacco, and Alcohol: A Case for Multifactor Disease

Table 1

Association between HPV¹ E6 and/or E7 status with head and neck cancer risk factors.

Risk Factors	Oral cavity cases (𝑁=170)			Oropharynx cases (𝑁=74)			Controls (𝑁=428)
	HPV E6/E7+; N (%)	HPV E6/E7−; N (%)	Adjusted; 𝑃 value	HPV E6/E7+; N (%)	HPV E6/E7−; N (%)	Adjusted; 𝑃 value	HPV E6/E+; N (%)	HPV E6/E7−; N (%)	Adjusted 𝑃 value
HPV prevalence	16 (9.4)	154 (90.6)		47 (63.5)	27 (36.5)		31 (7.2)	397 (92.8)
Age^3	Oral cavity positive versus oropharyngeal positive: 𝑃 value = 0.01; oral cavity negative versus oropharyngeal negative: 𝑃 value = 0.33
Mean	64.7 (3.6)	61.2 (1.5)	0.35	54.5 (2.1)	58.2 (2.7)	0.28	56.8 (2.7)	58.1 (0.7)	0.63
Range	45–86	21–93		36–82	29–85		18–77	22–93
≤55	6 (37.5)	55 (35.7)	0.96	29 (61.7)	11 (40.7)	0.05	14 (45.2)	166 (41.8)	0.83
>55	10 (62.5)	99 (64.3)		18 (38.3)	16 (59.3)		17 (54.8)	231 (58.2)
Gender
Male	14 (87.5)	79 (51.3)	0.03	40 (85.1)	19 (70.4)	0.04	21 (67.7)	247 (62.2)	0.10
Female	2 (12.5)	75 (48.7)		7 (14.9)	8 (29.6)		10 (32.3)	150 (37.8)
Education^3
<12	5 (31.3)	34 (22.4)	0.58	5 (10.9)	11 (40.7)	0.07	2 (6.5)	52 (13.1)	0.87
12–15	9 (56.3)	87 (57.2)	0.50	32 (69.6)	10 (37.0)	0.51	18 (58.1)	226 (57.1)	0.61
≥16	2 (12.5)	31 (20.4)	Ref	9 (19.6)	6 (22.2)	Ref	11 (35.5)	118 (29.8)	Ref
Tobacco^4
Never	3 (18.8)	54 (35.3)	Ref	8 (17.4)	2 (7.4)	Ref	10 (34.5)	150 (37.9)	Ref
>0.0–30	3 (18.8)	41 (26.8)	0.59	19 (41.3)	6 (22.2)	0.85	15 (51.7)	127 (32.1)	0.24
>30	10 (62.5)	58 (37.9)	9.94	19 (41.3)	19 (70.4)	0.37	4 (13.8)	119 (30.1)	0.24
Alcohol^5
Never	3 (18.8)	57 (37.3)	Ref	6 (13.0)	2 (7.4)	Ref	14 (45.2)	170 (43.0)	Ref
1–21	5 (31.3)	54 (35.3)	0.92	27 (58.7)	10 (37.0)	0.67	15 (48.4)	166 (42.0)	0.95
>21	8 (50.0)	42 (27.5)	0.64	13 (28.3)	15 (55.6)	0.14	2 (6.5)	59 (14.9)	0.30
Number of Partners
0-1	6 (42.9)	60 (42.9)	Ref	3 (7.1)	4 (16.7)	Ref	10 (34.5)	122 (32.3)	Ref
2–10	5 (35.7)	59 (42.1)	0.56	23 (54.8)	13 (54.2)	0.55	16 (55.2)	186 (49.2)	0.64
≥11	3 (21.4)	21 (15.0)	0.66	16 (38.1)	7 (29.2)	0.70	3 (10.3)	70 (18.5)	0.21
Oral-genital sex
Yes	3 (37.5)	39 (49.4)	0.83	24 (92.3)	8 (50.0)	0.02	16 (51.6)	184 (53.8)	0.27
No	5 (62.5)	40 (50.6)		2 (7.7)	8 (50.0)		15 (48.4)	158 (46.2)
Stage
I/II	8 (50.0)	58 (39.5)	Ref	3 (6.8)	5 (19.2)	Ref
III/IV	8 (50.0)	89 (60.5)	0.30	41 (93.2)	21 (80.8)	0.19
Grade
Poor/undifferentiated	5 (33.3)	23 (16.2)	0.13	25 (55.6)	3 (12.5)	0.004
well/moderate	10 (66.7)	119 (83.8)	Ref	20 (44.4)	21 (87.5)	Ref
Nodal status
Yes	7 (43.7)	54 (36.0)	0.87	42 (89.4)	20 (74.1)	0.07
No	9 (56.3)	96 (64.0)	Ref	5 (10.6)	7 (25.9)	Ref

¹Positive versus negative for HPV-16 or HPV-18 or HPV-33 E6 and/or E7 status; ²adjusted for age, gender, tobacco, and alcohol; ³years; ⁴pack-years; ⁵drinks/week.