Characteristics of the study participants
In this study, a total of 23,724 women from Shanghai Zhoupu Hospital underwent outpatient gynecological examinations and were tested for HPV and TCT. Participants were between 15 and 94 years old, with an average age of 36.76.
Among the 23,724 participants,3,816 were HPV infection positive, the total HPV infection rate was 16.08% (3,816 / 23,724), and the HR-HPV positive rate was 14.18% (3,363) / 23,724). Therefore, 88.13% of HPV infections are caused by HR-HPV.
Among all 23,724 participants, 18.98% (4,502/23,724) women were TCT positive, of whom, 17.71% (4,202/23,724), 0.06% (15/23,724), 0.53% (125/23,724), 0.67% (159/23,724), and 0.004% (1/23,724) had ASCs, AGCs, HSILs, LSILs and, Cervical adenocarcinoma, respectively.
Figure 1 compares the distribution of TCT cytology results between HPV positive and negative infection rates. Among 3,816 positive HPV infections, there were 31.63% (1,207/3,816) TCT positive rate and 68.37% (2,609/3,816) TCT negative. Whereas, among 19,908 negative HPV infections, there were 16.55% (3,295/19,908) TCT positive infection and 83.45% (3,295/19,908) TCT negative among 19,908 negative HPV infections. There was a significant difference in TCT results between HPV positive group and HPV negative group (P<0.001). The positive rate of TCT in HPV-positive patients (31.63%) is much higher than that in HPV-negative patients (16.55%).
Single-type and multiple-type HPV infections in women of different ages
Distribution of HPV single-type and multiple-type infection in different age groups are shown in Table 1. Among 2,513 women aged 50-60 years, the HPV positive rate was 19.18% (482 / 2,513), which was higher than that in other age groups.
Single-type infection is much higher than multiple-type infection, which are 91.20% (3,480/3,816) and 8.8% (336/3,816) respectively (χ2 test P < 0.0001). Among single-type HPV infections, it is more common in women aged 50-60 and women under 30, which are 16.63% (418/2,513) and 15.37% (1,163/7,568), respectively. Among multi-type HPV infections, women aged over 60 and 50-60 are more common, with 2.67% (29/10,88) and 2.55% (64/2,513) respectively.
Table 1 Distribution of HPV single-type and multiple-type infection in different age groups
Age (years)
|
N
|
HPV Positive, n(%)
|
Single-type infection, n(%)
|
Multiple-type infection,n(%)
|
<30
|
7568
|
1271(16.79)
|
1163(15.37)
|
108(1.43)
|
30-40
|
7866
|
1127(14.33)
|
1043(13.26)
|
84(1.07)
|
40-50
|
4689
|
741(15.8)
|
690(14.72)
|
51(1.09)
|
50-60
|
2513
|
482(19.18)
|
418(16.63)
|
64(2.55)
|
>60
|
1088
|
195(17.92)
|
166(15.26)
|
29(2.67)
|
Total
|
23724
|
3816
|
3480
|
336
|
Single-type and multiple-type infection rates in every subtype of all 21 HPV subtypes
Table 2 and Figure 2 show the comparison of the distribution of single-type and multiple-type infection rate of each subtype among all 21 HPV subtypes, and the first 15 was HR-HPV subtypes and the last 6 was LR-HPV ones. Here, the infection rate of each HPV subtype is calculated by calculating the ratio of the number of people infected by the HPV subtype to the total number of women (N = 23,724).
Among the 21 HPV subtypes, the top three highest prevalence rates were all high-risk HPV: HPV52, 58, and 16, with infection rates of 3.19%, 2.47% and 2.34%, respectively. Among single-type and multiple-type HPV infections, these three high-risk HPVs were also the most common.
Table 2 Distribution of single-type and multiple-type infection rate of each subtype among all 21 HPV subtypes
HPV subtype
|
Positive
n(%)
|
Single-type
infection n(%)
|
Multi-type
infection n(%)
|
HPV16
|
555(2.34)
|
363(1.53)
|
192(0.81)
|
HPV18
|
205(0.86)
|
125(0.53)
|
80(0.34)
|
HPV31
|
171(0.72)
|
S105(0.44)
|
66(0.28)
|
HPV33
|
255(1.07)
|
118(0.5)
|
137(0.58)
|
HPV35
|
69(0.29)
|
43(0.18)
|
26(0.11)
|
HPV39
|
354(1.49)
|
209(0.88)
|
145(0.61)
|
HPV45
|
53(0.22)
|
30(0.13)
|
23(0.1)
|
HPV51
|
355(1.5)
|
228(0.96)
|
127(0.54)
|
HPV52
|
756(3.19)
|
494(2.08)
|
262(1.1)
|
HPV53
|
373(1.57)
|
227(0.96)
|
146(0.62)
|
HPV56
|
121(0.51)
|
65(0.27)
|
56(0.24)
|
HPV58
|
586(2.47)
|
346(1.46)
|
240(1.01)
|
HPV59
|
70(0.3)
|
37(0.16)
|
33(0.14)
|
HPV66
|
195(0.82)
|
108(0.46)
|
87(0.37)
|
HPV68
|
192(0.81)
|
112(0.47)
|
80(0.34)
|
HPV6
|
147(0.62)
|
127(0.54)
|
20(0.08)
|
HPV11
|
126(0.53)
|
108(0.46)
|
18(0.08)
|
HPV42
|
54(0.23)
|
51(0.21)
|
3(0.01)
|
HPV43
|
26(0.11)
|
24(0.1)
|
2(0.01)
|
HPV44
|
95(0.4)
|
88(0.37)
|
7(0.03)
|
HPV81
|
379(1.6)
|
356(1.5)
|
23(0.1)
|
The first 15 were HR-HPV subtypes and the last 6 were LR-HPV subtype.
Trend of infection rates of different HPV subtypes in 2014-2019
Table 3 and Figure 3 show the trends of HPV subtype infections from 2014 to 2019. In the past six years, hpv52, 58, and 16 were in the top three with the highest infection rate. The trend of most subtypes infection rates had a significant difference (P < 0.05), except hpv42 and 43 (Table 3).
As shown in Figure 3, from 2014 to 2019, the prevalence of most HR-HPV was higher than that of LR-HPV. Most of the highest prevalence rate of each HPV subtype occurred in 2018. Especially HPV52 has the highest prevalence rate (3.38%) of all HPV subtypes.
Table 3 Secular trends in infection rates of different HPV subtypes from 2014 to 2019
HPV subtype
|
2014,n (%)
|
2015,n (%)
|
2016,n (%)
|
2017,n (%)
|
2018,n (%)
|
2019,n (%)
|
P-value for trend
|
HPV16
|
28(2.54)
|
105(2.59)
|
106(2.06)
|
161(2.53)
|
154(2.19)
|
1(3.23)
|
0.0179
|
HPV18
|
13(1.18)
|
40(0.99)
|
27(0.53)
|
59(0.93)
|
66(0.94)
|
0(0)
|
0.0229
|
HPV31
|
9(0.82)
|
38(0.94)
|
39(0.76)
|
47(0.74)
|
38(0.54)
|
0(0)
|
0.0147
|
HPV33
|
23(2.08)
|
45(1.11)
|
62(1.21)
|
67(1.05)
|
58(0.82)
|
0(0)
|
0.0105
|
HPV35
|
10(0.91)
|
9(0.22)
|
11(0.21)
|
21(0.33)
|
18(0.26)
|
0(0)
|
0.0125
|
HPV39
|
16(1.45)
|
67(1.65)
|
77(1.5)
|
94(1.48)
|
100(1.42)
|
0(0)
|
0.0177
|
HPV45
|
7(0.63)
|
4(0.1)
|
8(0.16)
|
21(0.33)
|
13(0.18)
|
0(0)
|
0.0323
|
HPV51
|
15(1.36)
|
64(1.58)
|
67(1.3)
|
112(1.76)
|
97(1.38)
|
0(0)
|
0.0219
|
HPV52
|
39(3.53)
|
141(3.48)
|
128(2.49)
|
209(3.29)
|
238(3.38)
|
1(3.23)
|
0.0207
|
HPV53
|
23(2.08)
|
73(1.8)
|
70(1.36)
|
91(1.43)
|
116(1.65)
|
0(0)
|
0.0167
|
HPV56
|
5(0.45)
|
19(0.47)
|
11(0.21)
|
49(0.77)
|
37(0.53)
|
0(0)
|
0.0496
|
HPV58
|
27(2.45)
|
100(2.47)
|
132(2.57)
|
155(2.44)
|
172(2.44)
|
0(0)
|
0.0189
|
HPV59
|
4(0.36)
|
12(0.3)
|
13(0.25)
|
24(0.38)
|
17(0.24)
|
0(0)
|
0.0217
|
HPV66
|
8(0.72)
|
28(0.69)
|
37(0.72)
|
54(0.85)
|
68(0.97)
|
0(0)
|
0.0286
|
HPV68
|
7(0.63)
|
32(0.79)
|
36(0.7)
|
53(0.83)
|
64(0.91)
|
0(0)
|
0.0259
|
HPV6
|
4(0.36)
|
23(0.57)
|
35(0.68)
|
35(0.55)
|
50(0.71)
|
0(0)
|
0.0273
|
HPV11
|
4(0.36)
|
25(0.62)
|
16(0.31)
|
43(0.68)
|
38(0.54)
|
0(0)
|
0.0327
|
HPV42
|
3(0.27)
|
1(0.02)
|
3(0.06)
|
27(0.42)
|
20(0.28)
|
0(0)
|
0.1135
|
HPV43
|
1(0.09)
|
1(0.02)
|
5(0.1)
|
11(0.17)
|
8(0.11)
|
0(0)
|
0.0631
|
HPV44
|
8(0.72)
|
8(0.2)
|
16(0.31)
|
31(0.49)
|
32(0.45)
|
0(0)
|
0.0319
|
HPV81
|
24(2.17)
|
89(2.2)
|
92(1.79)
|
102(1.6)
|
71(1.01)
|
1(3.23)
|
0.0132
|
Total
|
278
|
924
|
991
|
1466
|
1475
|
3
|
|
The first 15 was HR-HPV subtypes and the last 6 were LR-HPV subtypes
Distribution of TCT positive infections in different age groups
Comparison of the distribution of TCT positive infections in different age groups are shown in Table 4. Among women over 60 years old, the positive rate of TCT (23.05%) was the highest. And among women under 30, the positive rate of TCT (17.83%) was the lowest. Besides, the distributions of both HSIL and ASC increased significantly in different age groups (P < 0.0001, Table 4).
Table 4 Distribution of TCT positive infections in different age groups
Age (years)
|
N
|
NILM, n(%)
|
LSIL ,n(%)
|
HSIL ,n(%)
|
AGC ,n(%)
|
ASC ,n(%)
|
CERVICAL ADENOCARCINOMA, n(%)
|
TCT positive, n (%)
|
<30
|
7567
|
6218(82.17)
|
55(0.73)
|
8(0.11)
|
4(0.05)
|
1282(16.94)
|
0(0)
|
1349(17.83)
|
30-40
|
7866
|
6437(81.83)
|
47(0.6)
|
34(0.43)
|
3(0.04)
|
1345(17.1)
|
0(0)
|
1429(18.17)
|
40-50
|
4689
|
3755(80.08)
|
37(0.79)
|
38(0.81)
|
4(0.09)
|
855(18.23)
|
0(0)
|
934(19.92)
|
50-60
|
2513
|
1974(78.55)
|
17(0.68)
|
30(1.19)
|
3(0.12)
|
489(19.46)
|
0(0)
|
539(21.45)
|
>60
|
1089
|
838(76.95)
|
3(0.28)
|
15(1.38)
|
1(0.09)
|
231(21.21)
|
1(0.09)
|
251(23.05)
|
Total
|
23724
|
19222
|
159
|
125
|
15
|
4202
|
1
|
4502
|
Distribution of HPV and TCT infection rates in different age groups from 2014 to 2019
Table 5 and Figure 4 show the distribution of HPV and TCT infection rates in different age groups from 2014 to 2019.
We found that the HPV positive rate of all women has changed significantly from 2014 to 2019 (P-value for trend< 0.05). whereas, there was no significant difference in the TCT positive rate during this period (Table 5).
From figure 4, except for 2018, the number of TCT infections was lower than the number of HPV infections. In 2018, there were 384 HPV infections and 1,166 TCT infections among women under 30 years of age, and 324 HPV infections and 1,188 TCT infections among women 30-40 years old.
Table 5 Distribution of HPV and TCT infection rates in different age groups from 2014 to 2019
Age (years)
|
2014,n (%)
|
2015,n (%)
|
2016,n (%)
|
2017,n (%)
|
2018,n (%)
|
2019,n (%)
|
P-value for trend
|
HPV positive
|
|
|
|
|
|
|
|
<30
|
57(27.8)
|
214(31.56)
|
234(31.45)
|
381(35.91)
|
384(34.13)
|
1(33.33)
|
0.0226
|
30-40
|
52(25.37)
|
208(30.68)
|
220(29.57)
|
322(30.35)
|
324(28.8)
|
1(33.33)
|
0.0192
|
40-50
|
61(29.76)
|
127(18.73)
|
149(20.03)
|
195(18.38)
|
209(18.58)
|
0(0)
|
0.0131
|
50-60
|
21(10.24)
|
104(15.34)
|
101(13.58)
|
117(11.03)
|
138(12.27)
|
1(33.33)
|
0.0166
|
>60
|
14(6.83)
|
25(3.69)
|
40(5.38)
|
46(4.34)
|
70(6.22)
|
0(0)
|
0.0241
|
Total
|
205
|
678
|
744
|
1061
|
1125
|
3
|
-
|
TCT positive
|
|
|
|
|
|
|
|
<30
|
14(17.5)
|
56(23.14)
|
43(20.38)
|
70(21.08)
|
1166(32.07)
|
0(0)
|
0.2866
|
30-40
|
20(25)
|
73(30.17)
|
44(20.85)
|
103(31.02)
|
1188(32.67)
|
1(100)
|
0.2667
|
40-50
|
17(21.25)
|
57(23.55)
|
58(27.49)
|
72(21.69)
|
730(20.08)
|
0(0)
|
0.2353
|
50-60
|
15(18.75)
|
46(19.01)
|
47(22.27)
|
52(15.66)
|
379(10.42)
|
0(0)
|
0.1849
|
>60
|
14(17.5)
|
10(4.13)
|
19(9)
|
35(10.54)
|
173(4.76)
|
0(0)
|
0.1773
|
Total
|
80
|
242
|
211
|
332
|
3636
|
1
|
-
|
The relationship between TCT test results and each HPV subtype infections
Figure 5 shows the Distribution of every HPV subtype infection rates among NILM, AGC, ASC, LSIL, and HSIL. There are more TCT positives in HR-HPV patients than LR-HPV patients. Few HPV-positive patients have AGC infection (red). Among the four abnormal TCT results, ASC infection (Dark blue) has the highest number of infections.
The last column of Table 6 shows the top three HPV subtypes with the highest TCT positive rate were HPV 16, 6, and 42 (42.52%, 39.46% and 38.89%), among the patients who received both HPV and TCT examinations. This is different from the second column of Table 6. Among HPV-positive patients, the subtypes with the highest prevalence are 52, 58, and 16.
In Table 6, among the five cytopathies, the HPV infection rates corresponding to NILM, LSIL, HSIL, AGC and ASC were 66.08% (3,495 / 19,222), 119.50% (190/159), 115.20% (144/125), and 63.99%, respectively (5/15) and 31.72% (1,333/4,202)). And the HPV infection rates corresponding to LSIL and HSIL were both greater than 100%, which means that there are many mixed multi-subtype HPV infections in these two types of cytological lesions.
In NILM, the most common HPV-positive subtypes are 51, 39, and 16. In HSIL, the most common HPV-positive subtypes are 45,33 and 58. In LSIL, the most common HPV-positive subtypes are 56,35 and 59. In ASC, the most common HPV-positive subtypes are 6,42 and 43. Very few HPV positive were found in AGC. (Table 6) (Figure 5).
Table 6 Different HPV subtype infection rates among NILM, AGC, ASC, LSIL, and HSIL, respectively
HPV subtype
|
N
|
NILM (%)
N=19,222
|
LSIL (%)
N=159
|
HSIL (%)
N=125
|
AGC (%)
N=15
|
ASC (%)
N=4202
|
CERVICAL ADENOCARCINOMA (%)
N=1
|
TCT positive, n (%)
|
HPV16
|
555
|
319(57.48)
|
23(4.14)
|
51(9.19)
|
0(0)
|
162(29.19)
|
0(0)
|
236(42.52)
|
HPV18
|
205
|
138(67.32)
|
7(3.41)
|
4(1.95)
|
0(0)
|
56(27.32)
|
0(0)
|
67(32.68)
|
HPV31
|
171
|
118(69.01)
|
6(3.51)
|
4(2.34)
|
0(0)
|
43(25.15)
|
0(0)
|
53(30.99)
|
HPV33
|
255
|
161(63.14)
|
10(3.92)
|
13(5.1)
|
0(0)
|
71(27.84)
|
0(0)
|
94(36.86)
|
HPV35
|
69
|
45(65.22)
|
4(5.8)
|
2(2.9)
|
0(0)
|
18(26.09)
|
0(0)
|
24(34.78)
|
HPV39
|
354
|
252(71.19)
|
13(3.67)
|
3(0.85)
|
1(0.28)
|
85(24.01)
|
0(0)
|
102(28.81)
|
HPV45
|
53
|
34(64.15)
|
1(1.89)
|
4(7.55)
|
0(0)
|
14(26.42)
|
0(0)
|
19(35.85)
|
HPV51
|
355
|
256(72.11)
|
11(3.1)
|
4(1.13)
|
1(0.28)
|
83(23.38)
|
0(0)
|
99(27.89)
|
HPV52
|
756
|
505(66.8)
|
27(3.57)
|
16(2.12)
|
1(0.13)
|
207(27.38)
|
0(0)
|
251(33.2)
|
HPV53
|
373
|
259(69.44)
|
18(4.83)
|
6(1.61)
|
0(0)
|
90(24.13)
|
0(0)
|
114(30.56)
|
HPV56
|
121
|
77(63.64)
|
8(6.61)
|
1(0.83)
|
0(0)
|
35(28.93)
|
0(0)
|
44(36.36)
|
HPV58
|
586
|
398(67.92)
|
21(3.58)
|
26(4.44)
|
1(0.17)
|
140(23.89)
|
0(0)
|
188(32.08)
|
HPV59
|
70
|
48(68.57)
|
4(5.71)
|
1(1.43)
|
0(0)
|
17(24.29)
|
0(0)
|
22(31.43)
|
HPV66
|
195
|
135(69.23)
|
7(3.59)
|
2(1.03)
|
0(0)
|
51(26.15)
|
0(0)
|
60(30.77)
|
HPV68
|
192
|
131(68.23)
|
5(2.6)
|
2(1.04)
|
0(0)
|
54(28.12)
|
0(0)
|
61(31.77)
|
HPV6
|
147
|
89(60.54)
|
7(4.76)
|
1(0.68)
|
0(0)
|
50(34.01)
|
0(0)
|
58(39.46)
|
HPV11
|
126
|
89(70.63)
|
5(3.97)
|
0(0)
|
0(0)
|
32(25.4)
|
0(0)
|
37(29.37)
|
HPV42
|
54
|
33(61.11)
|
2(3.7)
|
1(1.85)
|
0(0)
|
18(33.33)
|
0(0)
|
21(38.89)
|
HPV43
|
26
|
16(61.54)
|
1(3.85)
|
1(3.85)
|
0(0)
|
8(30.77)
|
0(0)
|
10(38.46)
|
HPV44
|
95
|
67(70.53)
|
1(1.05)
|
0(0)
|
0(0)
|
27(28.42)
|
0(0)
|
28(29.47)
|
HPV81
|
379
|
295(77.84)
|
9(2.37)
|
2(0.53)
|
1(0.26)
|
72(19)
|
0(0)
|
84(22.16)
|
Total
|
5137
|
3465
|
190
|
144
|
5
|
1333
|
0
|
1672
|
The first 15 were HR-HPV subtypes and the last 6 were LR-HPV subtypes
Comparison of TCT positive infection in single-type and multiple-type HPV infection
In Figure 6, according to the classification of HPV infection in single-type and multiple-type, the positive rates of TCT were 31.61% (1,100/3,480) and 31.84% (107/336), respectively. The proportions of TCT positive between single-type and multiple-type are almost the same.