Background
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Screening would be undertaken with the test having higher sensitivity (hr-HPV testing);
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85-90% of women would be returned immediately to routine screening with a negative hr-HPV test without incurring the cost of cytology, which would be reserved only for those with a positive hr-HPV;
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The high-volume screening of samples would be undertaken with a non-subjective test that can be automated, while the subjective, labour-intensive test would be restricted to high-risk samples that could be examined with greater vigilance because of the reduced number to be interpreted;
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It represents a more robust screening approach that could serve the additional purpose of post-vaccination surveillance in the population[13];
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The recommended cervical cancer screening interval can be extended, as the long term risk of CIN3 or worse in women with a negative hr-HPV test is much lower than those who have a negative cytology, thus providing greater reassurance to women and also resulting in potential cost savings[10].
Methods/Design
Trial Design
British Columbia Population Based Cervical Cancer Screening Program
Study Population and Recruitment
Study Protocol (Figure 1)
Colposcopy
Histology
Randomization and Blinding
Statistical Considerations
Sample Size
Analysis
Primary Outcome Measures
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Control and intervention arms: Cumulative incident ≥ CIN3 detected up to and including four years in both the control arm and the intervention arm
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Control and safety check arms: Incident ≥ CIN2 detected at two years. If the number of ≥ CIN2 in the safety-check group exceeds 0.8 times that in the control arm at the 2 year screen, then the trial will conclude and women in the four year intervention arm will be recalled at two years for their exit screen.
Secondary Outcome Measures
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Rates of ≥ CIN2 and hr-HPV respectively at initial screen in control and safety/intervention arms;
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Rates of incident ≥ CIN2 at two years in control arm and at four years in intervention arm;
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The total estimated cost per woman screened and the total estimated cost per quality-adjusted life-year gained for each technology;
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Clearance of hr-HPV infection in women who are hr-HPV-positive and cytology negative at initial screen.
Ethical Issues
Discussion
Preliminary Findings
Arm | ||||
---|---|---|---|---|
Control (%) | Safety (%) | Intervention (%) | Total (%) | |
Age Group (years)
| ||||
25-29 | 141 (7%) | 153 (7.2%) | 127 (6.3%) | 421 (6.8%) |
30-34 | 172 (8.5%) | 172 (8.1%) | 166 (8.3%) | 510 (8.3%) |
35-39 | 284 (14.1%) | 315 (14.9%) | 269 (13.4%) | 868 (14.1%) |
40-44 | 318 (15.8%) | 351 (16.6%) | 319 (15.9%) | 988 (16.1%) |
45-49 | 357 (17.7%) | 371 (17.5%) | 376 (18.7%) | 1104 (18%) |
50-54 | 309 (15.3%) | 312 (14.7%) | 283 (14.1%) | 904 (14.7%) |
55-59 | 252 (12.5%) | 241 (11.4%) | 279 (13.9%) | 772 (12.6%) |
60-65 | 186 (9.2%) | 204 (9.6%) | 193 (9.6%) | 583 (9.5%) |
Cultural Group
| ||||
Aboriginal | 61 (3%) | 58 (2.7%) | 48 (2.4%) | 167 (2.7%) |
Black | 10 (0.5%) | 10 (0.5%) | 7 (0.3%) | 27 (0.4%) |
British | 1113 (55.1%) | 1178 (55.6%) | 1118 (55.6%) | 3409 (55.4%) |
Chinese | 181 (9%) | 211 (10%) | 198 (9.8%) | 590 (9.6%) |
French | 196 (9.7%) | 178 (8.4%) | 174 (8.6%) | 548 (8.9%) |
Southeast Asian | 9 (0.4%) | 8 (0.4%) | 4 (0.2%) | 21 (0.3%) |
Northern European | 136 (6.7%) | 144 (6.8%) | 160 (8%) | 440 (7.2%) |
Southern European | 135 (6.7%) | 119 (5.6%) | 97 (4.8%) | 351 (5.7%) |
Eastern European | 251 (12.4%) | 259 (12.2%) | 243 (12.1%) | 753 (12.2%) |
Western European | 316 (15.7%) | 355 (16.8%) | 335 (16.7%) | 1006 (16.4%) |
Other | 316 (15.7%) | 320 (15.1%) | 282 (14%) | 918 (14.9%) |
Marital Status
| ||||
Divorced | 176 (8.8%) | 209 (9.9%) | 212 (10.6%) | 597 (9.8%) |
Married | 1324 (66.3%) | 1381 (65.7%) | 1274 (64%) | 3979 (65.3%) |
Single | 286 (14.3%) | 292 (13.9%) | 285 (14.3%) | 863 (14.2%) |
Widowed | 30 (1.5%) | 25 (1.2%) | 25 (1.3%) | 80 (1.3%) |
Common-law | 182 (9.1%) | 195 (9.3%) | 196 (9.8%) | 573 (9.4%) |
Educational History
| ||||
Elementary/Incomplete High School | 41 (2.1%) | 55 (2.6%) | 46 (2.3%) | 142 (2.3%) |
High School (complete) | 296 (14.8%) | 292 (14%) | 283 (14.3%) | 871 (14.3%) |
Trade Certificate/College | 591 (29.6%) | 629 (30.1%) | 608 (30.6%) | 1828 (30.1%) |
University (incomplete) | 134 (6.7%) | 121 (5.8%) | 131 (6.6%) | 386 (6.4%) |
University graduate or higher | 935 (46.8%) | 991 (47.5%) | 917 (46.2%) | 2843 (46.8%) |
Employment
| ||||
Currently Working | 1588 (78.8%) | 1666 (78.8%) | 1556 (77.7%) | 4810 (78.5%) |
On Disability | 58 (2.9%) | 61 (2.9%) | 49 (2.5%) | 168 (2.8%) |
On Social Assistance | 4 (0.2%) | 7 (0.3%) | 9 (0.5%) | 20 (0.3%) |
Arm | ||||
---|---|---|---|---|
Control (%) | Safety (%) | Intervention (%) | Total (%) | |
Smoked Regularly (Ever)
| 790 (41.3%) | 746 (37.7%) | 764 (40.4%) | 2300 (39.8%) |
Mean Age of Started Smoking in Years (N = 2300)
| 16.4 | 16.6 | 16.5 | 16.5 |
Current Smoker | 150 (19.1%) | 135 (18.2%) | 144 (18.8%) | 429 (18.7%) |
History of Sexual Intercourse
| ||||
Never sexually active | 8 (0.4%) | 9 (0.4%) | 6 (0.3%) | 23 (0.4%) |
Mean Age of Sexual Debut in Years (N = 5984)
| 18.8 | 18.8 | 18.7 | 18.8 |
Lifetime No. Male Sexual Partners (N = 6013)
| ||||
0 | 1 (0.1%) | 4 (0.2%) | 4 (0.2%) | 9 (0.1%) |
1 | 420 (21.2%) | 429 (20.8%) | 422 (21.4%) | 1271 (21.1%) |
2-5 | 650 (32.9%) | 757 (36.6%) | 685 (34.8%) | 2092 (34.8%) |
6-10 | 482 (24.4%) | 458 (22.2%) | 458 (23.3%) | 1398 (23.2%) |
11-50 | 391 (19.8%) | 393 (19%) | 376 (19.1%) | 1160 (19.3%) |
51-99 | 22 (1.1%) | 23 (1.1%) | 22 (1.1%) | 67 (1.1%) |
99+ | 11 (0.6%) | 3 (0.1%) | 2 (0.1%) | 16 (0.3%) |
Male Sexual Partners in Past Six Months (N = 5990)
| ||||
0 | 294 (14.9%) | 322 (15.6%) | 324 (16.6%) | 940 (15.7%) |
1 | 1618 (82.1%) | 1681 (81.4%) | 1586 (81.2%) | 4885 (81.6%) |
2+ | 59 (3%) | 62 (3%) | 44 (2.3%) | 165 (2.8%) |
History of Pregnancy
| ||||
Ever Pregnant before (N = 6004) | 1588 (81.1%) | 1654 (79.9%) | 1602 (81.1%) | 4844 (80.7%) |
Mean age at first pregnancy (N = 4844)
| 26.5 | 26.5 | 26.3 | 26.5 |
Mean Number of Pregnancies (N = 4844)
| 2.7 | 2.6 | 2.7 | 2.7 |
Mean Age of Menarche (N = 6087)
| 12.8 | 12.9 | 12.8 | 12.8 |
Oral Contraceptive
| ||||
Ever | 1765 (87.4%) | 1824 (86.1%) | 1743 (86.6%) | 5332 (86.7%) |
Mean Years on Oral Contraceptives (N = 5332)
| 9.0 | 8.9 | 9.0 | 9.0 |
Contraception Method
| ||||
Barrier (Ever) | 1550 (76.8%) | 1638 (77.3%) | 1529 (76%) | 4717 (76.7%) |
Barrier (Current) | 276 (13.7%) | 293 (13.8%) | 253 (12.6%) | 822 (13.4%) |
Vaginal (Ever) | 197 (9.8%) | 269 (12.7%) | 243 (12.1%) | 709 (11.5%) |
Vaginal (Current) | 7 (0.3%) | 10 (0.5%) | 11 (0.5%) | 28 (0.5%) |
Hormonal (Ever) | 1771 (87.7%) | 1829 (86.3%) | 1746 (86.8%) | 5346 (86.9%) |
Hormonal (Current) | 286 (14.2%) | 291 (13.7%) | 268 (13.3%) | 845 (13.7%) |
Permanent (Ever) | 659 (32.6%) | 689 (32.5%) | 654 (32.5%) | 2002 (32.6%) |
Permanent (Current) | 576 (28.5%) | 626 (29.5%) | 556 (27.6%) | 1758 (28.6%) |
Rhythm/Withdrawal (Ever) | 204 (10.1%) | 222 (10.5%) | 176 (8.7%) | 602 (9.8%) |
Rhythm/withdrawal (Current) | 53 (2.6%) | 54 (2.5%) | 39 (1.9%) | 146 (2.4%) |
Duration of HRT for Menopause in Years (N = 241)
| 4.2 | 4.5 | 5.6 | 4.7 |
Age Strata | Cytology Negative (%) | Cytology ASC-US (%) | Cytology ATY (%) | Cytology LSIL (mild) (%) | Cytology ASC-H (%) | Cytology HSIL (%) | Cytology Smear Unsatisfactory (%) | Total |
---|---|---|---|---|---|---|---|---|
25-29 | 123 (87.2) | 4 (2.8) | 0 (0.0) | 6 (4.3) | 2 (1.4) | 2 (1.4) | 4 (2.8) | 141 |
30-34 | 157 (91.3) | 1 (0.6) | 1 (0.6) | 9 (5.2) | 0 (0.0) | 2 (1.2) | 2 (1.2) | 172 |
35-39 | 270 (95.1) | 6 (2.1) | 0 (0.0) | 5 (1.8) | 1 (0.4) | 1 (0.4) | 1 (0.4) | 284 |
40-44 | 302 (95.0) | 3 (0.9) | 1 (0.3) | 6 (1.9) | 0 (0.0) | 3 (0.9) | 3 (0.9) | 318 |
45-49 | 336 (94.1) | 9 (2.5) | 0 (0.0) | 5 (1.4) | 1 (0.3) | 4 (1.1) | 2 (0.6) | 357 |
50-54 | 296 (95.8) | 4 (1.3) | 0 (0.0) | 2 (0.6) | 2 (0.6) | 2 (0.6) | 2 (0.6) | 309 |
55-59 | 244 (96.8) | 0 (0.0) | 0 (0.0) | 3 (1.2) | 0 (0.0) | 0 (0.0) | 5 (2.0) | 252 |
60+ | 180 (96.8) | 1 (0.5) | 1 (0.5) | 0 (0.0) | 1 (0.5) | 2 (1.1) | 1 (0.5) | 186 |
Total | 1908 (94.5) | 28 (1.4) | 4 (0.2) | 36 (1.8) | 7 (0.3) | 16 (0.8) | 20 (1.0) | 2019 |
Safety Check Arm | Intervention Arm | |||||||
---|---|---|---|---|---|---|---|---|
Age Strata | hr-HPV Negative (%) | hr-HPV Positive (%) | hr-HPV Unsatis (%) | Total | hr-HPV Negative (%) | hr-HPV Positive (%) | hr-HPV Unsatis (%) | Total |
25-29 | 117 (76.5) | 36 (23.5) | 0 (0.0) | 153 | 95 (74.8) | 31 (24.4) | 1 (0.8) | 127 |
30-34 | 151 (87.8) | 21 (12.2) | 0 (0.0) | 172 | 146 (88.0) | 20 (12.0) | 0 (0.0) | 166 |
35-39 | 284 (90.2) | 31 (9.8) | 0 (0.0) | 315 | 239 (88.8) | 30 (11.2) | 0 (0.0) | 269 |
40-44 | 324 (92.3) | 26 (7.4) | 1 (0.3) | 351 | 300 (94.0) | 18 (5.6) | 1 (0.3) | 319 |
45-49 | 358 (96.5) | 13 (3.5) | 0 (0.0) | 371 | 354 (94.1) | 19 (5.1) | 3 (0.8) | 376 |
50-54 | 293 (93.9) | 18 (5.8) | 1 (0.3) | 312 | 267 (94.3) | 15 (5.3) | 1 (0.4) | 283 |
55-59 | 232 (96.3) | 9 (3.7) | 0 (0.0) | 241 | 265 (95.0) | 13 (4.7) | 1 (0.4) | 279 |
60+ | 195 (95.6) | 9 (4.4) | 0 (0.0) | 204 | 188 (97.4) | 4 (2.1) | 1 (0.5) | 193 |
Total | 1954 (92.2) | 163 (7.7) | 2 (0.1) | 2119 | 1854 (92.1) | 150 (7.5) | 8 (0.4) | 2012 |