Association of plasma AFB1-lys detection with persistent HPV detection
Frequencies and percentages of HPV detections (“no detection”, “incident detection” and “persistent detection”) in women with and without plasma AFB1-lys detection and mean (STD) and median (IQR) of plasma AFB1-lys concentration (pg/uL) among women with different HPV detections are shown in Table 2. There was a trend of significantly increasing plasma AFB1-lys concentrations among women who had no detection, incident detection, or persistent detection for any HPV type (p = 0.036), HR-HPV types (p = 0.020), or vaccine-unprotected HR-HPV types (p = 0.017) (Table 2). Similar trends in increasing plasma AFB1-lys concentrations were observed for some other groups of HPV types, however, these were not significant (Table 2).
Table 2. Frequency and percentage of HPV detection in 67 women with and without plasma AFB1-lys detection, and mean (standard deviation, or STD) and median (interquartile range, or IQR) of plasma AFB1-lys concentration (pg/uL).
HPV
|
HPV detection category
|
Plasma AFB1-lys
concentration (pg/uL)
|
Plasma AFB1-lys
detection
|
N, Mean (STD)
|
Median (IQR)
|
P- Value13
|
No (N=27)
|
Yes (N=40)
|
P-Value
|
n (%)
|
n (%)
|
Any HPV1
|
No Detection
|
23, 0.030 (0.042)
|
0.000 (0.000-0.066)
|
0.036
|
14 (51.9)
|
9 (22.5)
|
0.04311
|
|
Incident Detection
|
32, 0.050 (0.043)
|
0.052 (0.000-0.088)
|
|
10 (37.0)
|
22 (55.0)
|
|
|
Persistent Detection
|
12, 0.078 (0.068)
|
0.081 (0.014-0.098)
|
|
3 (11.1)
|
9 (22.5)
|
|
HR-HPV2
|
No Detection
|
30, 0.034 (0.044)
|
0.000 (0.000-0.065)
|
0.020
|
17 (63.0)
|
13 (32.5)
|
0.03811
|
|
Incident Detection
|
26, 0.049 (0.041)
|
0.050 (0.000-0.091)
|
|
8 (29.6)
|
18 (45.0)
|
|
|
Persistent Detection
|
11, 0.086 (0.066)
|
0.082 (0.027-0.098)
|
|
2 (7.4)
|
9 (22.5)
|
|
IARC HR-HPV3
|
No Detection
|
35, 0.046 (0.057)
|
0.035 (0.000-0.073)
|
0.410
|
17 (63.0)
|
18 (45.0)
|
0.36112
|
|
Incident Detection
|
24, 0.048 (0.042)
|
0.046 (0.000-0.093)
|
|
8 (29.6)
|
16 (40.0)
|
|
|
Persistent Detection
|
8, 0.058 (0.042)
|
0.078 (0.014-0.093)
|
|
2 (7.4)
|
6 (15.0)
|
|
A9 HPV4
|
No Detection
|
45, 0.045 (0.053)
|
0.035 (0.000-0.073)
|
0.395
|
20 (74.1)
|
25 (62.5)
|
0.56712
|
|
Incident Detection
|
17, 0.055 (0.043)
|
0.067 (0.000-0.094)
|
|
5 (18.5)
|
12 (30.0)
|
|
|
Persistent Detection
|
5, 0.054 (0.049)
|
0.082 (0.000-0.089)
|
|
2 (7.4)
|
3 (7.5)
|
|
Non-HPV 16 A95
|
No Detection
|
48, 0.044 (0.052)
|
0.031 (0.000-0.073)
|
0.171
|
22 (81.5)
|
26 (65.0)
|
0.17512
|
|
Incident Detection
|
15, 0.062 (0.041)
|
0.079 (0.023-0.095)
|
|
3 (11.1)
|
12 (30.0)
|
|
|
Persistent Detection
|
9, 0.047 (0.054)
|
0.045 (0.000-0.093)
|
|
2 (7.4)
|
2 (5.0)
|
|
A7 HPV6
|
No Detection
|
55, 0.048 (0.050)
|
0.047 (0.000-0.085)
|
0.097
|
23 (85.2)
|
32 (80.0)
|
0.23612
|
|
Incident Detection
|
8, 0.025 (0.029)
|
0.016 (0.000-0.050)
|
|
4 (14.8)
|
4 (10.0)
|
|
|
Persistent Detection
|
4, 0.096 (0.067)
|
0.086 (0.050-0.142)
|
|
0 (0.0)
|
4 (10.0)
|
|
Non-HPV 18 A77
|
No Detection
|
59, 0.049 (0.048)
|
0.047 (0.000-0.085)
|
0.090
|
23 (85.2)
|
36 (90.0)
|
0.66112
|
|
Incident Detection
|
7, 0.024 (0.031)
|
0.000 (0.000-0.059)
|
|
4 (14.8)
|
3 (7.5)
|
|
|
Persistent Detection
|
1, 0.186 (-)
|
0.186 (0.186-0.186)
|
|
0 (0.0)
|
1 (2.5)
|
|
Vaccine-protected HR-HPV8
|
No Detection
|
41, 0.046 (0.054)
|
0.040 (0.000-0.073)
|
0.505
|
18 (66.7)
|
23 (57.5)
|
0.62512
|
|
Incident Detection
|
18, 0.047 (0.045)
|
0.042 (0.000-0.094)
|
|
7 (25.9)
|
11 (27.5)
|
|
|
Persistent Detection
|
8, 0.058 (0.042)
|
0.078 (0.014-0.093)
|
|
2 (7.4)
|
6 (15.0)
|
|
Vaccine-unprotected HR-HPV9
|
No Detection
|
47, 0.038 (0.044)
|
0.023 (0.000-0.079)
|
0.017
|
23 (85.2)
|
24 (60.0)
|
0.06412
|
|
Incident Detection
|
16, 0.054 (0.040)
|
0.063 (0.008-0.090)
|
|
4 (14.8)
|
12 (30.0)
|
|
|
Persistent Detection
|
4, 0.137 (0.071)
|
0.133 (0.077-0.198)
|
|
0 (0.0)
|
4 (10.0)
|
|
LR-HPV10
|
No Detection
|
44, 0.045 (0.047)
|
0.038 (0.000-0.081)
|
0.414
|
19 (70.4)
|
25 (62.5)
|
0.28412
|
|
Incident Detection
|
22, 0.057 (0.055)
|
0.058 (0.000-0.091)
|
|
7 (25.9)
|
15 (37.5)
|
|
|
Persistent Detection
|
1, 0.000 (-)
|
0.000 (0.000-0.000)
|
|
1 (3.7)
|
0 (0.0)
|
|
1Any HPV: HPV 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 62, 64, 66, 67, 68, 70, 71, 72, 73, 81, 82, 83, 84, CP6108, IS39
2HR-HPV (High-Risk HPV): HPV 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 67, 68, 69, 70, 73, 82, IS39
3IARC HR-HPV: HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66
4A9 HPV: HPV 16, 31, 33, 35, 52, 58
5Non-HPV 16 A9: HPV 31, 33, 35, 52, 58
6A7 HPV: HPV 18, 39, 45, 59, 68
7Non-HPV 18 A7: HPV 39, 45, 59, 68
8Vaccine-protected HR-HPV: HPV 16, 18, 31, 33, 45, 52, 58
9Vaccine-unprotected HR-HPV: HPV 26, 35, 39, 51, 53, 56, 59, 66, 67, 68, 69, 70, 73, 82, IS39
10LR-HPV (Low-Risk HPV): HPV 6, 11, 40, 42, 54, 55, 61, 62, 64, 71, 72, 81, 83, 84, CP6108
11P-value from Chi-square test
12P-value from Fisher’s exact test
13P-value from Wilcoxon rank sum test
In addition, compared with women without detectable plasma AFB1-lys, women with detectable plasma AFB1-lys demonstrated significantly higher percentages of detection for any HPV type (22.5% vs. 11.1% for persistent detection and 55.0% vs. 37.0% for incident detection, p = 0.043) and HR-HPV type (22.5% vs. 7.4% for persistent detection and 45.0% vs. 29.6% for incident detection, p = 0.038). Similar patterns of HPV detections between women with and without detectable plasma AFB1-lys were found for all other HPV combination types except for LR-HPV types. However these were not statistically significant, possibly due to small sample sizes.
A total of 13 episodes of type-specific persistent HPV detections occurred in 12 women (Table 3). Among these episodes, 12 were HR-HPV types, including 10 episodes that occurred in 9 of 40 women with detectable plasma AFB1-lys, and 2 episodes occurring in 2 of 27 women without detectable plasma AFB1-lys (Table 3). HPV 18 was the most frequently detected persistent type (3 episodes), all occurring in women with detectable plasma AFB1-lys (Table 3).
Table 3
Episodes of type-specific persistent HPV detection and corresponding plasma AFB1-lys detection/concentration.
Subject
ID
|
Type-specific HPV Detection
|
Plasma AFB1-lys
|
Type
|
Enrollment
|
12-month
visit
|
24-month
visit
|
Persistent
detection
|
Detection
|
Concentration
(pg/uL)
|
M028
|
HPV 162
|
pos
|
missing
|
pos
|
2-year
|
yes
|
0.082
|
M060
|
HPV 182
|
neg
|
pos
|
pos
|
1-year
|
yes
|
0.027
|
M120
|
HPV 182
|
pos
|
pos
|
pos
|
2-year
|
yes
|
0.098
|
M1891
|
HPV 182
|
neg
|
pos
|
pos
|
1-year
|
yes
|
0.073
|
M069
|
HPV 522
|
neg
|
pos
|
pos
|
1-year
|
no
|
0.000
|
M121
|
HPV 522
|
pos
|
pos
|
neg
|
1-year
|
yes
|
0.097
|
M168
|
HPV 533
|
pos
|
pos
|
neg
|
1-year
|
yes
|
0.080
|
M066
|
HPV 582
|
pos
|
pos
|
neg
|
1-year
|
no
|
0.000
|
M154
|
HPV 582
|
neg
|
pos
|
pos
|
1-year
|
yes
|
0.089
|
M114
|
HPV 682
|
neg
|
pos
|
pos
|
1-year
|
yes
|
0.186
|
M173
|
HPV 702
|
pos
|
pos
|
neg
|
1-year
|
yes
|
0.209
|
M1891
|
HPV 702
|
pos
|
pos
|
neg
|
1-year
|
yes
|
0.073
|
M155
|
HPV 832
|
pos
|
pos
|
neg
|
1-year
|
no
|
0.000
|
1 M189 had two episodes of type-specific persistent HPV detections, one episode with HPV 18 |
and one episode with HPV 70 |
2 High-Risk HPV type |
3 Low-Risk HPV type |
Ordinal logistic regression analysis revealed that detectable plasma AFB1-lys was associated with a higher risk of persistent detection for any HPV type (OR = 3.03, 95%CI = 1.08–8.55, P = 0.036), HR-HPV types (OR = 3.63, 95%CI = 1.30-10.13, P = 0.014), and HR-HPV types not included in the 9-valent HPV vaccine (Vaccine-unprotected HR-HPV types) (OR = 4.46, 95%CI = 1.13–17.58, P = 0.032) after adjustment for established and suspected confounders (Table 4). The proportional odds assumption was validated for each ordinal logistic regression model. There was no statistically significant association of detectable plasma AFB1-lys with persistent detection of sub-groups of HR-HPV types, for HR-HPV types protected by the 9-valent HPV vaccine (Vaccine-protected HR-HPV types), or for low-risk (LR) HPV types (Supplemental Table 1).
Table 4
Ordinal logistic regression analyses of Any HPV, HR-HPV, Vaccine-protected HR-HPV, and Vaccine-unprotected HR-HPV detection (persistent detection vs. incidence detection vs. no detection) with plasma AFB1-lys detection and demographic/behavioral characteristics of women5.
Variables included in the model
|
Any HPV1
|
HR-HPV2
|
Vaccine-protected
HR-HPV3
|
Vaccine-unprotected
HR-HPV4
|
OR (95% CI)
|
P-value
|
OR (95% CI)
|
P-value
|
OR (95% CI)
|
P-value
|
OR (95% CI)
|
P-value
|
Plasma AFB1-lys detection
|
3.03 (1.08–8.55)
|
0.036
|
3.63 (1.30–10.13)
|
0.014
|
1.55 (0.54–4.44)
|
0.413
|
4.46 (1.13–17.58)
|
0.032
|
Age
|
0.88 (0.79–0.98)
|
0.017
|
0.92 (0.83–1.02)
|
0.127
|
0.93 (0.83–1.03)
|
0.180
|
0.91 (0.79–1.05)
|
0.188
|
Married
|
0.28 (0.08–0.94)
|
0.039
|
0.63 (0.20–2.03)
|
0.442
|
0.38 (0.11–1.32)
|
0.128
|
0.58 (0.15–2.28)
|
0.437
|
More than secondary school education
|
1.13 (0.27–4.76)
|
0.868
|
0.72 (0.17–2.95)
|
0.645
|
1.41 (0.33–5.98)
|
0.643
|
1.10 (0.17–6.98)
|
0.918
|
Home ownership
|
2.43 (0.71–8.31)
|
0.156
|
1.60 (0.48–5.30)
|
0.441
|
1.45 (0.41–5.18)
|
0.563
|
1.78 (0.38–8.34)
|
0.465
|
Walking distance to health care ≥ 60 mins
|
1.46 (0.27–7.77)
|
0.657
|
0.83 (0.16–4.18)
|
0.820
|
0.46 (0.08–2.74)
|
0.397
|
2.27 (0.36–14.06)
|
0.380
|
Number of lifetime sex partners
|
1.07 (0.86–1.34)
|
0.544
|
1.10 (0.88–1.36)
|
0.405
|
1.02 (0.81–1.29)
|
0.880
|
0.99 (0.77–1.27)
|
0.918
|
Age of first sex
|
1.16 (0.98–1.38)
|
0.088
|
1.08 (0.92–1.28)
|
0.351
|
1.18 (0.99–1.40)
|
0.066
|
0.74 (0.57–0.97)
|
0.031
|
1Any HPV: HPV 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 62, 64, 66, 67, 68, 70, 71, 72, 73, 81, 82, 83, 84, CP6108, IS39 |
2HR-HPV (High-Risk HPV): HPV 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 67, 68, 69, 70, 73, 82, IS39 |
3Vaccine-protected HR-HPV: HPV 16, 18, 31, 33, 45, 52, 58 |
4Vaccine-unprotected HR-HPV: HPV 26, 35, 39, 51, 53, 56, 59, 66, 67, 68, 69, 70, 73, 82, IS39 |