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Table 1 Cumulative incident risk of CIN3+ and HPV16 positivity frequency by the numbers of high-methylation sites of HPV 16

From: Risk stratification of HPV 16 DNA methylation combined with E6 oncoprotein in cervical cancer screening: a 10-year prospective cohort study

HPV gene

Numbers of sites*

Numbers of individual

10-year cumulative CIN3+

HPV16 positivity frequency#

Incidence rate

HR (95%CI)

p§

Once

Twice

Three times

p

L1

0

26

7.7 (2.1, 24.1)

1 (Ref.)

< 0.001

76.9 (58.0, 89.0)

19.2 (8.5, 37.9)

3.8 (0.7, 18.9)

< 0.001

1

28

21.4 (10.2, 39.5)

3.3 (0.7, 16.5)

 

40.0 (23.4, 59.3)

20.0 (8.9, 39.1)

40.0 (23.4, 59.3)

 

2–3

8

75.0 (40.9, 92.9)

14.6 (2.9, 74.6)

 

25.0 (7.1, 59.1)

0 (0, 32.4)

75.0 (40.9, 92.9)

 

LCR

0

29

6.9 (1.9, 22.0)

1 (Ref.)

0.001

55.2 (37.6, 71.6)

20.7 (9.8, 38.4)

24.1 (12.2, 42.1)

0.296

1

21

23.8 (10.6, 45.1)

3.9 (0.8, 20.2)

 

63.2 (41.0, 80.9)

10.5 (2.9, 31.4)

26.3 (11.8, 48.8)

 

2–3

12

58.3 (32.0, 80.7)

12.8 (2.6, 62.5)

 

36.4 (15.2, 64.6)

18.2 (5.1, 47.7)

45.5 (21.3, 72.0)

 

L1+LCR

0

14

0 (0, 21.5)

---

 

71.4 (45.4, 88.3)

21.4 (7.6, 47.6)

7.1 (1.3, 31.5)

0.004

1

22

9.1 (2.5, 27.8)

1 (Ref.)

< 0.001

59.1 (38.7, 76.7)

18.2 (7.3, 38.5)

22.7 (10.1, 43.4)

 

2

14

28.6 (11.7, 54.7)

3.7 (0.7, 20.0)

 

50.0 (25.4, 74.6)

16.7 (4.7, 44.8)

33.3 (13.8, 60.9)

 

3–6

12

66.7 (39.1,86.2)

12.0 (2.5,57.7)

 

27.3 (9.7,56.6)

9.1 (1.6,37.7)

63.6 (35.4,84.8)

 
  1. HPV human papillomavirus, L1 Late gene 1, LCR long control region, CIN3+ cervical intraepithelial neoplasia grade 3 or worse (CIN3+), HR hazard ratio, CI confidence interval
  2. *Number of high methylation sites out of six significant sites of HPV 16: CpG 5602, 6650 and 7034 in L1 gene and 7461, 31 and 37 in LCR gene
  3. #HPV genotyping test was conducted on all HC2 positive samples to determine HPV 16 positivity frequency in three visits of follow-up, i.e., in 2005, 2010, and 2014. Therefore, HPV16 positivity frequency may be once, twice, and three times in three tests during 2005–2014
  4. §p value for log-rank test; p value for chi-square test