Background
Methods
General female population
Women with CIN3 and ICC
HPV testing and genotyping
Statistical analyses
Ethical approval
Results
General female population
HPV type | Normal (n = 2272) | Abnormal (n = 196) | Total (n = 2505)a
| |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Single | Multiple | Total | (%) | Single | Multiple | Total | (%) | Single | Multiple | Total | (%) | |
HPV-
| - | - | 1750 | (77) | - | - | 76 | (39) | - | - | 1850 | (74) |
HPV+
| 358 | 164 | 522 | (23) | 70 | 50 | 120 | (61) | 437 | 218 | 655 | (26) |
High-risk
| ||||||||||||
16
| 48 | 30 | 78 | (3.4) | 15 | 13 | 28 | (14) | 65 | 44 | 109 | (4.4) |
18
| 26 | 27 | 53 | (2.3) | 2 | 9 | 11 | (5.6) | 29 | 37 | 66 | (2.6) |
31
| 14 | 7 | 21 | (0.9) | 4 | 3 | 7 | (3.6) | 19 | 10 | 29 | (1.2) |
33
| 9 | 12 | 21 | (0.9) | 6 | 4 | 10 | (5.1) | 16 | 17 | 33 | (1.3) |
35
| 3 | 6 | 9 | (0.4) | 3 | 2 | 5 | (2.6) | 6 | 8 | 14 | (0.6) |
39
| 11 | 5 | 16 | (0.7) | 0 | 6 | 6 | (3.1) | 11 | 11 | 22 | (0.9) |
45
| 9 | 19 | 28 | (1.2) | 1 | 8 | 9 | (4.6) | 10 | 27 | 37 | (1.5) |
51
| 15 | 14 | 29 | (1.3) | 6 | 8 | 14 | (7.1) | 21 | 22 | 43 | (1.7) |
52
| 16 | 12 | 28 | (1.2) | 3 | 3 | 6 | (3.1) | 19 | 15 | 34 | (1.4) |
56
| 17 | 14 | 31 | (1.4) | 4 | 8 | 12 | (6.1) | 21 | 23 | 44 | (1.8) |
58
| 14 | 13 | 27 | (1.2) | 11 | 6 | 17 | (8.7) | 25 | 19 | 44 | (1.8) |
59
| 21 | 19 | 40 | (1.8) | 4 | 2 | 6 | (3.1) | 26 | 21 | 47 | (1.9) |
68
| 4 | 5 | 9 | (0.4) | 3 | 1 | 4 | (2.0) | 7 | 6 | 13 | (0.5) |
Any
| 214b
| 125 | 339b
| (15) | 62 | 42 | 104 | (53) | 282b
| 169 | 451b
| (18) |
Possibly high-risk
| ||||||||||||
26
| 1 | 1 | 2 | (0.1) | 0 | 0 | 0 | (0.0) | 1 | 1 | 2 | (0.1) |
30
| 3 | 7 | 10 | (0.4) | 1 | 1 | 2 | (1.0) | 4 | 8 | 12 | (0.5) |
34
| 0 | 1 | 1 | (0.0) | 0 | 0 | 0 | (0.0) | 0 | 1 | 1 | (0.0) |
53
| 2 | 4 | 6 | (0.3) | 1 | 2 | 3 | (1.5) | 3 | 6 | 9 | (0.4) |
66
| 4 | 13 | 17 | (0.7) | 0 | 3 | 3 | (1.5) | 4 | 16 | 20 | (0.8) |
67
| 15 | 24 | 39 | (1.7) | 1 | 9 | 10 | (5.1) | 17 | 33 | 50 | (2.0) |
69
| 0 | 3 | 3 | (0.1) | 0 | 1 | 1 | (0.5) | 0 | 4 | 4 | (0.2) |
70
| 8 | 13 | 21 | (0.9) | 0 | 2 | 2 | (1.0) | 8 | 15 | 23 | (0.9) |
73
| 1 | 5 | 6 | (0.3) | 0 | 2 | 2 | (1.0) | 1 | 7 | 8 | (0.3) |
82
| 2 | 2 | 4 | (0.2) | 1 | 1 | 2 | (1.0) | 3 | 3 | 6 | (0.2) |
85
| 0 | 1 | 1 | (0.0) | 0 | 1 | 1 | (0.5) | 0 | 2 | 2 | (0.1) |
Any
| 36 | 62 | 98 | (4.3) | 4 | 19 | 23 | (11.7) | 41 | 81 | 122 | (4.9) |
Low-risk
| ||||||||||||
6
| 8 | 5 | 13 | (0.6) | 1 | 0 | 1 | (0.5) | 9 | 5 | 14 | (0.6) |
11
| 6 | 4 | 10 | (0.4) | 1 | 1 | 2 | (1.0) | 7 | 5 | 12 | (0.5) |
Other
| 94 | 99 | 193 | (9.4) | 2 | 24 | 26 | (13) | 98 | 125 | 223 | (8.9) |
Any
| 108 | 106 | 214 | (9.4) | 4 | 25 | 29 | (17) | 114 | 133 | 247 | (10) |
Characteristic | N womena
| HPV-positive (%) | AdjustedbPR | 95% CI | AdjustedcPR | 95% CI |
---|---|---|---|---|---|---|
Age-group (years)
| ||||||
≤24 | 885 | 289 (32.7) | 1 | - | 1 | - |
25-34 | 852 | 223 (26.2) | 0.82 | 0.71-0.95 | 0.81 | 0.70-0.94 |
35-44 | 435 | 85 (19.5) | 0.61 | 0.49-0.75 | 0.57 | 0.46-0.71 |
≥45 | 333 | 58 (17.4) | 0.53 | 0.42-0.69 | 0.51 | 0.39-0.65 |
χ
2
1
for trend
|
p < 0.001
|
p < 0.001
| ||||
Hospital where examined
| ||||||
Thimphu | 1638 | 460 (28.1) | 1 | - | 1 | - |
Lungthenphu | 867 | 195 (22.5) | 0.81 | 0.70-0.94 | 0.82 | 0.71-0.95 |
Type of invitation
| ||||||
Clinic | 1835 | 483 (26.3) | 1 | - | 1 | - |
Door to door | 670 | 172 (25.7) | 1.06 | 0.91-1.24 | 1.08 | 0.92-1.26 |
Ethnic group
| ||||||
Scharchop | 949 | 264 (27.8) | 1 | - | 1 | - |
Ngalop | 586 | 180 (30.7) | 1.11 | 0.95-1.30 | 1.11 | 0.94-1.30 |
Lhotsampa | 585 | 116 (19.8) | 0.69 | 0.57-0.83 | 0.70 | 0.57-0.85 |
Other | 371 | 88 (23.7) | 0.90 | 0.74-1.11 | 0.89 | 0.72-1.09 |
Education (yrs)
| ||||||
Illiterate | 1209 | 292 (24.2) | 1 | - | 1 | - |
1-9 | 512 | 132 (25.8) | 1.02 | 0.85-1.21 | 1.02 | 0.85-1.21 |
≥10 | 750 | 221 (29.5) | 1.07 | 0.92-1.24 | 1.09 | 0.94-1.28 |
χ
2
1
for trend
|
p = 0.415
|
p = 0.274
| ||||
Marital status
| ||||||
Married | 2298 | 586 (25.5) | 1 | - | 1 | - |
Single | 54 | 19 (35.2) | 1.22 | 0.84-1.76 | 1.60 | 1.14-2.24 |
Separated/widowed | 137 | 42 (30.7) | 1.34 | 1.04-1.74 | 1.31 | 1.01-1.69 |
Number of marriages
d
| ||||||
1 | 2209 | 549 (24.9) | 1 | - | 1 | - |
≥2 | 201 | 67 (33.3) | 1.62 | 1.32-1.99 | 1.27 | 0.86-1.86 |
Number of pregnancies
| ||||||
Nulliparous | 276 | 117 (42.4) | 1.46 | 1.23-1.74 | 1.50 | 1.26-1.78 |
1 | 776 | 228 (29.4) | 1 | - | 1 | - |
2 | 588 | 134 (22.8) | 0.85 | 0.70-1.03 | 0.83 | 0.68-1.01 |
≥3 | 839 | 163 (19.4) | 0.84 | 0.67-1.05 | 0.81 | 0.65-1.01 |
χ
2
1
for trend
e
|
p = 0.159
|
p = 0.090
| ||||
Age at first pregnancy
e
| ||||||
<19 | 554 | 145 (26.2) | 1 | - | 1 | - |
19-21 | 885 | 222 (25.1) | 0.93 | 0.78-1.11 | 0.98 | 0.82-1.17 |
≥22 | 754 | 155 (20.6) | 0.78 | 0.63-0.95 | 0.81 | 0.66-0.99 |
χ
2
1
for trend
|
p = 0.014
|
p = 0.041
| ||||
Contraceptive use
| ||||||
Never | 562 | 173 (30.8) | 1 | - | 1 | - |
Ever | 1860 | 458 (24.6) | 0.80 | 0.69-0.93 | 0.76 | 0.66-0.89 |
Hormonal only | 853 | 233 (27.3) | 0.82 | 0.69-0.96 | 0.78 | 0.66-0.92 |
Hormonal + other | 276 | 63 (22.8) | 0.79 | 0.61-1.02 | 0.74 | 0.57-0.95 |
Other only | 777 | 174 (22.4) | 0.78 | 0.65-0.94 | 0.75 | 0.63-0.90 |
Lifetime sexual partners
f
| ||||||
1 | 2228 | 566 (25.4) | 1 | - | 1 | - |
2 | 180 | 60 (33.3) | 1.54 | 1.24-1.92 | 1.54 | 1.24-1.92 |
≥3 | 26 | 10 (38.5) | 1.93 | 1.21-3.08 | 1.93 | 1.21-3.08 |
χ
2
1
for trend
|
p < 0.001
|
p < 0.001
| ||||
Husbands “extramarital” sexual relationships
d
| ||||||
No | 1966 | 481 (24.5) | 1 | - | 1 | - |
Yes, before marriage only | 308 | 95 (30.8) | 1.30 | 1.08-1.55 | 1.23 | 1.02-1.48 |
Yes, during marriage | 78 | 28 (35.9) | 1.71 | 1.27-2.31 | 1.49 | 1.09-2.05 |
Uncertain | 76 | 22 (29.0) | 1.02 | 0.72-1.47 | 1.00 | 0.70-1.43 |
History of receiving cash for sex
g
| ||||||
No | 2467 | 641 (26.0) | 1 | - | 1 | - |
Yes | 9 | 5 (55.6) | 2.77 | 1.55-4.95 | - | - |
Last PAP smear (yrs)
| ||||||
Never | 1367 | 418 (30.6) | 1 | - | 1 | - |
Ever | 1114 | 229 (20.6) | 0.77 | 0.66-0.90 | 0.77 | 0.66-0.90 |
Evidence of genital warts at visit
h
| ||||||
No | 2473 | 640 (25.9) | 1 | - | 1 | - |
Yes | 5 | 3 (60.0) | 2.17 | 1.06-4.45 | 2.23 | 1.09-4.59 |
Women with CIN3 and ICC
HPV type | Normala
| CIN3b
| Cancerb
| Cancer: normal cytology | |||
---|---|---|---|---|---|---|---|
(N = 2272) | (N = 211) | (N = 112) | Prevalence ratio (95% CI) | ||||
n
|
(% of HPV pos)
|
n
|
(% of HPV pos)
|
n
|
(% of HPV pos)
| ||
Any
| 522 | - | 183 | - | 99 | - | - |
16
| 78 | (15) | 109 | (60) | 62 | (63) | 5.8 (4.0-8.3) |
18
| 53 | (10) | 4 | (2) | 7 | (7) | 0.7 (0.4-1.5) |
16/18
| 127 | (24) | 113 | (62) | 69 | (70) | 5.0 (3.4-7.4) |
31
| 21 | (4) | 14 | (8) | 4 | (4) | 1.0 (0.4-2.5) |
33
| 21 | (4) | 12 | (7) | 2 | (2) | 0.5 (0.1-2.0) |
45
| 28 | (5) | 2 | (1) | 5 | (5) | 0.9 (0.4-2.2) |
52
| 28 | (5) | 2 | (1) | 3 | (3) | 0.6 (0.2-1.8) |
58
| 27 | (5) | 32 | (18) | 5 | (5) | 1.0 (0.4-2.2) |
16/18/31/33/45/52/58
| 235 | (45) | 168 | (92) | 87 | (88) | 6.7 (3.8-12.1) |
Other high-risk types
| 104 | (20) | 11 | (6) | 9 | (9) | 0.4 (0.2-0.8) |
Possible high-risk types
| 98 | (19) | 4 | (2) | 4 | (4) | 0.2 (0.1-0.6) |
Low-risk types
| 214 | (41) | 8 | (4) | 5 | (5) | 0.1 (0.0-0.2) |
Multiple infections
| 164 | (31) | 16 | (9) | 6 | (6) | 0.2 (0.1-0.4) |