Table 3.
Baseline and Cumulative Risk of High-grade Squamous Intraepithelial Lesion/Anal Intraepithelial Neoplasia Grades 2 and 3 by Candidate Biomarkers and Cytology
| Prevalence, % (95% CI) | 2-Year CumulativeRisk, % (95% CI) | 5-Year CumulativeRisk, % (95% CI) | |
|---|---|---|---|
| HR-HPV | |||
| Positive | 36.6 (31.2–42.4) | 46.5 (32.9–54.8) | 56.7 (32.9–64.2) |
| Negative | -- | 3.3 (0.0–9.4) | 7.3 (0.0–17.4) |
| HPV16/18 | |||
| Positive | 48.6 (40.3–56.9) | 59.6 (51.0–67.6) | 71.6 (61.6–80.9) |
| Negative | 16.7 (12.4–22.3) | 22.6 (14.8–29.6) | 29.3 (19.4–37.4) |
| Dual staina | |||
| Positive | 41.9 (35.7–48.4) | 52.0 (38.3–59.0) | 63.8 (38.3–70.6) |
| Negative | 6.8 (3.6–13.6) | 7.6 (2.9–13.6) | 9.4 (2.9–16.9) |
| HPV E6/E7 mRNA | |||
| Positive | 48.2 (40.8–55.7) | 60.3 (51.6–68.2) | 72.7 (60.3–83.1) |
| Negative | 11.2 (7.4–16.5) | 14.3 (9.0–20.7) | 20.0 (11.8–28.8) |
| Cytologyb | |||
| Positive | 41.0 (34.8–47.5) | 51.6 (39.9–59.4) | 61.4 (40.0–69.3) |
| Negative | 8.0 (4.2–14.7) | 11.9 (6.5–18.5) | 16.9 (7.8–26.7) |
| Biomarker combinations c | |||
| Dual stain orHPV16/18 | |||
| Positive | 38.6 (32.9–44.7) | 48.9 (41.3–55.0) | 59.9 (51.5–68.6) |
| Negative | 4.8 (1.8–12.0) | 4.8 (1.8–12.0) | 4.8 (1.8–12.0) |
| Dual stain andHPV16/18 | |||
| Positive | 58.3 (48.8–67.2) | 69.2 (59.3–77.3) | 81.5 (71.0–89.5) |
| Negative | 16.7 (12.5–21.9) | 21.2 (15.1–28.1) | 29.5 (20.9–36.9) |
| Dual stain orHPV E6/E7 mRNA | |||
| Positive | 39.7 (33.8–45.9) | 50.8 (36.1–58.0) | 62.0 (36.1–69.8) |
| Negative | 4.7 (1.8–11.9) | 5.8 (1.1–26.8) | 7.7 (1.1–30.8) |
| Dual stain andHPV E6/E7 mRNA | |||
| Positive | 53.1 (45.0–61.0) | 63.7 (55.9–71.6) | 76.4 (65.5–84.3) |
| Negative | 11.7 (7.9–16.8) | 14.2 (8.9–20.1) | 20.0 (11.9–28.2) |
| HPV16/18 orHPV E6/E7 mRNA | |||
| Positive | 45.2 (38.4–52.2) | 54.9 (48.9–64.7) | 67.6 (56.9–76.8) |
| Negative | 9.4 (5.7–15.0) | 12.8 (7.3–20.2) | 18.3 (9.5–28.7) |
The baseline prevalence was estimated by calculating the probability of high-grade squamous intraepithelial lesion/anal intraepithelial neoplasia grades 2 and 3 (HSIL/AIN2+) at enrollment from a logistic regression model. The cumulative risk was calculated by adding the probability of baseline HSIL/AIN2+ and the risk of incident disease, estimated from a Cox Proportional Hazards model.
Abbreviations: ASC-US+, atypical cells of undetermined significance or more severe cytology; CI, confidence interval; HPV, human papillomavirus; HR-HPV, high-risk HPV; mRNA, messenger RNA.
The threshold for a p16/Ki-67 dual stain was 1 positive cell.
The threshold for cytology was ASC-US+.
Biomarkers can either be combined as positive for at least 1 (ie, “or”) or positive for both (ie, “and”).