Progression from human papillomavirus (HPV) infection to cervical lesion or clearance in women (18–25 years): Natural history study in the control arm subjects of AS04-HPV-16/18 vaccine efficacy study in China between 2008 and 2016

Figures & data

Figure 1. General disposition of cervical HPV infections in the Chinese study. 6MPI: 6-month persistent infection; I: total number of HPV infections; N: total number of subjects with at least one cervical HPV infection.

Table 1. Risk of progression from 6MPI to CIN1+ or CIN2+ lesion of the same HPV type – Cox model multivariable analysis

	CIN1+			CIN2+
Category	N	Event	HR (95% CI)	N	Event	HR (95% CI)
HPV Type
Low-risk HPV	368	7	1.00 (REF)	368	4	1.00 (REF)
HPV-16	138	32	15.43 (6.61–36.02)	138	28	21.96 (7.48–64.42)
HPV-18	49	8	9.31 (3.25–26.72)	49	3	5.23 (1.13–24.20)
HPV-31	56	13	13.06 (4.95–34.49)	56	9	15.09 (4.49–50.70)
HPV-33	50	5	6.12 (1.80–20.84)	50	3	5.53 (1.18–25.98)
HPV-45	24	1	1.75 (0.19–15.79)	24	0	–
HPV-52	224	25	6.91 (2.86–16.70)	224	9	3.94 (1.28–12.11)
HPV-58	83	17	11.93 (4.67–29.97)	83	9	9.97 (3.23–30.79)
Other high-risk HPV	437	26	3.39 (1.39–8.27)	461	6	1.12 (0.32–3.90)
Previous cervical HPV infections
No previous cervical infection	798	81	1.00 (REF)	798	49	1.00 (REF)
Previous high-risk or low-risk HPV type^a	NA	NA	NA	631	22	0.60 (0.33–1.08)
Previous high-risk HPV type infection	541	47	0.89 (0.59–1.34)	NA	NA	NA
Previous low-risk HPV type infection	90	6	0.91 (0.33–2.97)	NA	NA	NA
Previous CIN1+
No	1,391	125	1.00 (REF)	1,390	69	1.00 (REF)
Yes high-risk or low-risk HPV type	38	9	5.84 (2.34–14.54)	39	2	2.12 (0.58–7.83)
Co-infection^b
No	853	56	1.00 (REF)	865	31	1.00 (REF)
Yes ≥1 high-risk HPV type	444	67	1.73 (1.16–2.58)	429	35	1.69 (0.97–2.95)
Yes only low-risk HPV type	132	11	1.41 (0.74–2.69)	135	5	1.34 (0.54–3.37)
CIN1+ associated with a different HPV type as the reference following the onset of the HPVI^b
No	1,364	127	1.00 (REF)	1,333	65	1.00 (REF)
Yes high-risk or low-risk HPV type	65	7	1.92 (0.69–5.37)	96	6	1.99 (0.70–5.64)
Age at infection (years)	1,429	134	0.97 (0.83–1.13)	1,429	71	1.11 (0.88–1.40)

^apooled high- and low-risk due to the low number of events in each category; ^bTime varying covariates. Survival time was limited to 72 months, thus 1 event was excluded from the analysis.

CI: confidence interval; CIN1+: cervical intraepithelial neoplasia grade 1 or greater; CIN2+: cervical intraepithelial neoplasia grade 2 or greater; Event: number of infections in Category with event; HPV: human papillomavirus; HPVI: HPV infection; HPV-16: HPV type 16; HPV-18: HPV type 18; HPV-31: HPV type 31; HPV-33: HPV type 33; HPV-45: HPV type 45; HPV-52: HPV type 52; HPV-58: HPV type 58; HR: hazard ratio; N: total number of infections; NA: not available.

Table 2. Probability of confirmed clearance from any HPV cervical infection – Cox model multivariable analysis

	HPV-039
Category	N	Event	HR (95% CI)
HPV Type
Low-risk HPV	374	229	1.00 (REF)
HPV-16	138	82	0.76 (0.59–0.98)
HPV-18	51	34	0.84 (0.59–1.19)
HPV-31	56	36	0.74 (0.53–1.01)
HPV-33	51	34	1.10 (0.74–1.65)
HPV-45	24	18	1.51 (0.94–2.44)
HPV-52	233	119	0.67 (0.54–0.84)
HPV-58	84	51	0.94 (0.68–1.31)
Other high-risk HPV	444	284	1.10 (0.92–1.31)
Duration of HPV infection
<6-month persistent (≤150 days)	26	14	1.00 (REF)
6-month persistent (>150 days)	1,429	873	0.12 (0.07–0.23)
Previous cervical HPV infections
No	804	552	1.00 (REF)
Yes ≥1 high-risk HPV type	557	284	0.80 (0.67–0.95)
Yes only low-risk HPV type	94	51	0.74 (0.55–1.01)
Co-infection^a
No	806	488	1.00 (REF)
Yes ≥1 high-risk HPV type	521	323	1.14 (0.92–1.42)
Yes only low-risk HPV type	128	76	1.37 (1.01–1.86)
Age at start of infection (years)	1,455	887	0.96 (0.93–0.99)

^aTime varying covariates. Exclusion of Transient infections and cervical HPV infections occurring at the last known visit.

CI: confidence interval; Event: number of infections with confirmed clearance; HPV: human papillomavirus; HPV-16: HPV type 16; HPV-18: HPV type 18; HPV-31: HPV type 31; HPV-33: HPV type 33; HPV-45: HPV type 45; HPV type 52; HPV-58: HPV type 58; HR: hazard ratio; N: total number of infections; REF: no value.