Pattern of multiple human papillomavirus infection and type competition: An analysis in healthy Chinese women aged 18–45 years

Figures & data

Figure 1. Type-specific HPV prevalence in women at enrollment visit before vaccination.

Table 1. Single, multiple HPV infection of women at enrollment visit before vaccination.

	No. HPV infection	Single HPV infection(%)	Multiple HPV infection(%)	p value
Total	1434	1072(74.8)	362(25.2)	NA
Age				.03
18–26	738	534(72.4)	204(27.6)
27–45	696	538(77.3)	158(22.7)
Mean(SD)	29.9 ± 7.6	30.1 ± 7.5	29.4 ± 7.6
Cervical Cytological				.002
Normal	997	771(77.3)	226(22.7)
Abnormal	437	301(68.9)	136(31.1)
ASC-US	193	142(73.6)	51(26.4)
ASC-H	11	8(72.7)	3(27.3)
LSIL	175	117(66.9)	58(33.1)
HSIL+	58	34(58.6)	24(41.4)
Histological				.045
CIN1	93	67(72.0)	26(28.0)
CIN2+	84	71(84.5)	13(15.5)

Table 2. Observed-to-expected ratio (O/E) of multiple infections.

Number of HPV coinfection	Observed number	Expected number	O/E(95%CI)
0	5933	5699.2	1.04(1.01–1.07)
1	1072	1462.9	0.73(0.69–0.78)
2	287	187.8	1.53(1.36–1.72)
3	59	16.1	3.66(2.84–4.73)
4	12	1	12.00(6.81–21.13)
5	4	0.1	40.00(15.01–106.58)

Figure 2. The log odds ratio with 95% CI for HPV vaccine type and nonvaccine-type interactions. (a) HPV 16, (b) HPV 18, (c) HPV 31, (d) HPV 33, (e) HPV 52, (f) HPV 58, (g) HPV6.

Table 3. The risk of cervical disease of multiple HPV infection.

HPV type	No. of women	CIN2+		HSIL+
		No.(%)	OR(95%CI)	No.(%)	OR(95%CI)
Any HPV
Single	1072	51(4.8)	1.00	34(3.2)	1.00
Multiple	362	33(9.1)	2.06(1.30, 3.25)	24(6.6)	2.21(1.29, 3.78)
Oncogenic type
Single	861	54(6.3)	1.00	37(4.3)	1.00
Multiple	227	30(13.2)	2.27(1.41, 3.64)	21(9.3)	2.26(1.29, 3.95)
Oncogenic type-HPV16/18 excluded
Single	687	24(3.9)	1.00	14(2.0)	1.00
Multiple	143	17(11.9)	3.68(1.92, 7.06)	8(5.6)	2.82(1.16, 6.87)
a9 sepcies
Single	658	63(9.6)	1.00	39(5.9)	1.00
Multiple	81	14(17.3)	2.04(1.08, 3.86)	14(17.3)	3.42(1.76, 6.66)
a7 sepcies
Single	284	19(6.7)	–	12(4.2)	–
Multiple	11	0(0)	NA	0(0)	NA
HPV16
Single	120	24(20.0)	1.00	17(14.2)	1.00
Multiple	74	14(18.9)	0.97(0.46, 2.03)	15(20.3)	1.61(0.74, 3.49)
HPV18
Single	37	5(13.5)	–	4(10.8)	1.00
Multiple	31	0(0)	NA	1(3.2)	0.28(0.03, 2.64)
HPV31
Single	22	3(13.6)	1.00	1(4.6)	1.00
Multiple	26	4(15.4)	1.13(0.22, 5.75)	2(7.7)	1.27(0.10, 16.70)
HPV33
Single	37	7(18.9)	1.00	3(8.1)	1.00
Multiple	33	4(12.1)	0.59(0.15, 2.23)	5(15.2)	1.97(0.43, 9.07)
HPV52
Single	221	4(1.8)	1.00	5(2.3)	1.00
Multiple	150	13(8.7)	5.21(1.66,16.3)	9(6.0)	2.76(0.91,8.41)
HPV52- HPV16/18 excluded
Single	221	4(1.8)	1.00	5(2.3)	1.00
Multiple	85	7(8.2)	4.83(1.38,16.97)	4(4.7)	2.13(0.56,8.14)
HPV58
Single	59	7(11.9)	1.00	4(6.8)	1.00
Multiple	49	10(20.4)	2.08(0.70, 6.18)	6(12.2)	2.10(0.53,8.22)

Table 4. The impact of multiple-type infections on the risk of cervical disease.

	CIN2+	HSIL+
	OR(95%CI)	OR(95%CI)
HPV16-HPV18
Negative	1.00	1.00
HPV 16 only	42.37(26.52–67.68)	45.76(27.07–77.36)
HPV 18 only	14.88(5.67–39.05)	16.25(5.54–47.66)
HPV 16 and 18	NE	85.71(8.52–862.79)
Synergy index	NE	1.41(0.14–14.69)
HPV16-HPV33
Negative	1.00	1.00
HPV 16 only	46.97(28.95–76.21)	47.58(27.81–81.41)
HPV 33 only	36.36(17.14–77.11)	26.49(10.55–66.5)
HPV 16 and 33	43.59(4.92–386.53)	144.02(24.96–830.96)
Synergy index	0.52(0.06–4.91)	1.98(0.34–11.65)
HPV16-HPV39
Negative	1.00	1.00
HPV 16 only	42.56(26.46–68.46)	41.31(24.71–69.08)
HPV 39 only	12.52(5.47–28.67)	2.02(0.27–14.91)
HPV 16 and 39	70.4(7.11–696.82)	85.08(8.54–847.46)
Synergy index	1.31(0.13–13.41)	2.03(0.2–20.96)
HPV16-HPV45
Negative	1.00	1.00
HPV 16 only	38(23.8–60.69)	44.13(26.29–74.09)
HPV 45 only	19.57(4.32–88.65)	27.34(5.97–125.22)
HPV 16 and 45	60.17(11.22–322.65)	34.59(4.01–298.69)
Synergy index	1.06(0.18–6.31)	0.48(0.05–4.74)
HPV16-HPV51
Negative	1.00	1.00
HPV 16 only	38.13(23.83–61.03)	42.07(25.13–70.41)
HPV 51 only	3.63(1.11–11.84)	1.58(0.21–11.62)
HPV 16 and 51	67.71(11.9–385.27)	35.44(3.98–315.92)
Synergy index	1.68(0.28–9.95)	0.83(0.09–7.94)
HPV16-HPV52
Negative	1.00	1.00
HPV 16 only	49.02(29.61–81.15)	54.07(30.69–95.28)
HPV 52 only	7.53(3.94–14.38)	8.05(3.83–16.9)
HPV 16 and 52	46.06(14.72–144.18)	64.55(20.23–206)
Synergy index	0.83(0.26–2.66)	1.06(0.33–3.41)
HPV16-HPV58
Negative	1.00	1.00
HPV 16 only	53.43(32.31–88.33)	48.22(27.94–83.22)
HPV 58 only	38.39(20.04–73.54)	19.16(8.15–45.07)
HPV 16 and 58	56.2(11.1–284.43)	117.52(27.62–499.94)
Synergy index	0.61(0.12–3.19)	1.78(0.41–7.68)
HPV18-HPV33
Negative	1.00	1.00
HPV 18 only	9.47(3.67–24.43)	9.5(3.32–27.16)
HPV 33 only	22.24(11.09–44.58)	16.71(7.27–38.42)
HPV 18 and 33	NE	30.77(3.5–270.18)
Synergy index	NE	1.23(0.12–12.58)
HPV31-HPV51
Negative
HPV 31 only	14.51(5.95–35.39)	8.14(2.45–27.01)
HPV 51 only	2.89(1.04–8.02)	1.72(0.42–7.13)
HPV 31 and 51	40.02(3.51–456.54)	NE
Synergy index	2.53(0.18–34.88)	NE
HPV31-HPV52
Negative
HPV 31 only	20.67(8.85–48.28)	6.3(1.48–26.77)
HPV 52 only	5.43(3.14–9.39)	4.99(2.69–9.27)
HPV 31 and 52	NE	45.58(4.59–452.37)
Synergy index	NE	4.8(0.38–60.75)
HPV31-HPV58
Negative
HPV 31 only	14.23(5.41–37.42)	6.11(5.9–6.32)
HPV 58 only	18.89(10.34–34.49)	15.6(15.36–15.83)
HPV 31 and 58	85.08(13.78–525.34)	NE
Synergy index	2.7(0.4–18.16)	NE
HPV33-HPV52
Negative
HPV 33 only	21.39(10.03–45.64)	13.72(5.24–35.91)
HPV 52 only	5(2.81–8.9)	4.53(2.33–8.81)
HPV 33 and 52	29.75(6.1–145.07)	64.47(15.94–260.76)
Synergy index	1.18(0.21–6.7)	3.9(0.79–19.32)
HPV52-HPV35
Negative
HPV 35 only	9.06(2.09–39.22)	11.96(2.74–52.15)
HPV 52 only	4.79(2.75–8.36)	5.49(3.01–10.02)
HPV 35 and 52	13.34(1.61–110.74)	NE
Synergy index	1.04(0.08–13.18)	NE
HPV52-HPV39
Negative
HPV 39 only	6.31(2.47–16.09)	1.48(0.2–10.84)
HPV 52 only	4.42(2.45–7.97)	5.05(2.72–9.36)
HPV 39 and 52	23.71(6.62–84.96)	8.47(1.1–65.24)
Synergy index	2.6(0.59–11.51)	1.65(0.14–19.38)
HPV52-HPV51
Negative
HPV 51 only	3.82(1.37–10.67)	2.39(0.58–9.95)
HPV 52 only	5.11(2.92–8.94)	5.68(3.11–10.36)
HPV 51 and 52	4.43(0.59–33.29)	NE
Synergy index	0.49(0.03–7.15)	NE
HPV52-HPV58
Negative
HPV 52 only	5.59(3.12–10.01)	5.32(2.79–10.16)
HPV 58 only	23.9(12.92–44.23)	14.02(6.41–30.67)
HPV 52 and 58	21.91(4.71–101.84)	26.38(5.65–123.13)
Synergy index	0.76(0.14–4)	1.46(0.27–7.91)
HPV58-HPV51
Negative
HPV 51 only	3.34(1.2–9.32)	1.95(0.47–8.07)
HPV 58 only	19.88(11.04–35.81)	13.71(6.77–27.77)
HPV 51 and 58	28.77(3.15–262.86)	NE
Synergy index	1.31(0.13–13.56)	NE
HPV58-HPV56
Negative
HPV 56 only	1.44(0.2–10.48)	NE
HPV 58 only	18.94(10.54–34.02)	13.19(6.53–26.67)
HPV 56 and 58	37.72(3.81–373.59)	NE
Synergy index	2.0(0.18–22.29)	NE

*only the synergy indices that can be estimated for CIN2+ or HSIL+ presented in this table.

Data availability statement

The data will be available beginning 6 months after the major findings from the final analysis of the study have been published, ending 2 y after. Proposals should be directed to [email protected]. To gain access, data requestors will need to sign a data access agreement.