Clinical validation of the Cervista^® high-risk human papillomavirus test in Chinese women from Fujian province: a cross-sectional study

Figures & data

Figure 1 Flowchart of participants in the study.

Abbreviations: ASC-US, atypical squamous cells of undetermined significance; CIN, cervical intraepithelial neoplasia; LSIL, low-grade squamous intraepithelial lesion; HR-HPV, high-risk human papillomavirus; NILM, negative for intraepithelial lesion or malignancy; TCT, thinprep cytologic test.

Figure 2 Prevalence of different HR-HPV infection styles and patients with different pathological results.

Notes: (A) Simple species infection was the most common style and species A9 was the most prevalent in HR-HPV infection. The most frequent HPV species in (B) NILM patients; (C) CIN1 patients; (D) CIN2 patients; (E) CIN3 patients; and (F) cervical cancer patients.
Abbreviations: CIN, cervical intraepithelial neoplasia; HR-HPV, high-risk human papillomavirus; NILM, negative for intraepithelial lesion or malignancy; SI, simple infection; DI, double infection; TI, triple infection.

Table 1 The distribution of HR-HPV infection in different cytology results (N=10,229) (n (%))

TCT test	HR-HPV test
	Negative (n=8,534)	Simple species A5/A6 infection (n=297)	Simple species A7 infection (n=314)	Simple species A9 infection (n=852)	Double species infection (n=182)	Triple species infection (n=50)	Overall HR-HPV infection (n=1,695)
NILM (n=9,253)	8,147 (79.65)	227 (2.22)	218 (2.13)	525 (5.13)	101 (0.99)	35 (0.34)	1,106 (10.81)
ASC-US (n=488)	265 (2.59)	26 (0.25)	40 (0.39)	121 (1.18)	29 (0.28)	7 (0.07)	223 (2.18)
ASC-H (n=20)	5/10,228a	1/10,228a	1/10,228a	12 (0.01)	1/10,228a	N/A	15 (0.15)
LSIL (n=208)	26 (0.25)	36 (0.35)	28 (0.27)	82 (0.80)	30 (0.29)	6 (0.059)	182 (1.78)
≥ HSIL (n=139)	4/10,228a	5/10,228a	16 (0.16)	96 (0.94)	18 (0.18)	N/A	135 (1.32)
AGC (n=119)	86 (0.84)	2/10,228a	11 (0.11)	15 (0.15)	3/10,228a	2/10,228a	33 (0.32)
AIS (n=2)	1/10,228a	N/A	N/A	1/10,228a	N/A	N/A	1/10,228a

Note:

a The number of cases ≤5 cases do not calculate the percentage.

Abbreviations: AGC, atypical glandular cells; AIS, adenocarcinoma in situ; ASC-H, atypical squamous cells cannot exclude HSIL; ASC-US, atypical squamous cells of undetermined significance; HR-HPV, high-risk human papillomavirus; HSIL, high-grade squamous intraepithelial lesion; LSIL, low-grade squamous intraepithelial lesion; NILM, negative for intraepithelial lesion or malignancy; TCT, thinprep cytologic test.

Table 2 Compare HR-HPV infection and cytology with pathological diagnosis in 9,748 patients

Subjects	Pathological diagnosis					χ^2a	P-value	χ^2b	P-value
	NILM (n=9,241)	CIN1 (n=228)	CIN2 (n=80)	CIN3 (n=129)	Cancer (n=70)
TCT
(n=9,748)
HPV-positive	837	177	73	117	68	7<290.071	<0.001	2<528.130	<0.001
(n=1,272)
HPV-negative	8<405	51	7	11	2
(n=8,476)
NILM
(n=8,882)
HPV-positive	667	38	10	16	4	1<604.354	<0.001	619.642	<0.001
(n=735)
HPV-negative	8<134	8	3	2	0
(n=8,147)
ASC-US
(n=411)
HPV-positive	105	58	24	12	3	30.743	<0.001	8.780	0.003
(n=202)
HPV-negative	176	28	2	3	0
(n=209)
ASC-H (n=18)
HPV-positive	4	0	2	5	2	3.348	0.067	1.582	0.208
(n=13)
HPV-negative	3	1	0	1	0
(n=5)
LSIL (n=186)
HPV-positive	42	75	19	18	7	4.343	0.045	2.392	0.211
(n=161)
HPV-negative	9	14	1	1	0
(n=25)
≥ HSIL
(n=134)
HPV-positive	2	4	17	63	44	0.193	1.000	0.688	0.953
(n=130)
HPV-negative	0	0	1	2	1
(n=4)
AGC (n=115)
HPV-positive	16	2	1	4	7	29.138	<0.001	25.813	<0.001
(n=30)
HPV-negative	83	0	0	2	0
(n=85)
AIS (n=2)
A HPV-positive	0	0	0	0	1	–	–	–	–
(n=1)
HPV-negative	0	0	0	0	1
(n=1)

Notes: χ^2a: The difference of patients with CIN2+ (included CIN2 or worse) between the HPV-positive and -negative species; χ^2b: the difference between the HPV-positive and -negative species in patients with CIN3+ (included CIN3 or worse).

Abbreviations: AIS, adenocarcinoma in situ; AGC, atypical glandular cells; ASC-H, atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion; ASC-US, atypical squamous cells of undetermined significance; CIN, cervical intraepithelial neoplasia; HPV, human papillomavirus; LSIL, low-grade squamous intraepithelial lesion; NILM, negative for intraepithelial lesion or malignancy; TCT, thinprep cytologic test.

Figure 3 Prevalence of HR-HPV infection and a cervical lesion in different age stratification.

Notes: (A) Prevalence of HR-HPV and different species in all age groups. (B) Prevalence of different cervical lesion in all age groups.
Abbreviations: CIN, cervical intraepithelial neoplasia; HR-HPV, high-risk human papillomavirus.

Figure 4 Combining Cervista^® with TCT to detect CIN2+/CIN3+.

Notes: (A) The cases of CIN2+ detected by co-testing were calculated in the baseline screening, first-year recall and subsequent follow-up, respectively. (B) The cases of CIN3+ detected by co-testing were calculated in the baseline screening, first-year recall and subsequent follow-up, respectively.
Abbreviations: CIN2+, cervical intraepithelial neoplasia 2 or worse; CIN3+, cervical intraepithelial neoplasia 3 or worse

Table 3 Comparing cytology and HR-HPV with co-testing in different degree of the cervical lesion (N=9,748)

	HR-HPV positive (95% CI)	TCT positive (95% CI)	HR-HPV+ TCT sequential screening (95% CI)
CIN1+
Sensitivity	86.07 (83.09–89.06)	84.02 (80.83–87.21)	97.48 (96.13–98.83)
Specificity	90.94 (90.36–91.52)	95.24 (94.80–95.67)	88.01 (87.35–88.67)
PPV	34.71 (32.11–37.32)	49.19 (45.86–52.52)	31.22 (28.96–33.49)
NPV	99.15 (98.96–99.35)	99.09 (98.90–99.29)	99.84 (99.75–99.92)
PLR	9.50 (8.83–10.23)	17.65 (15.99–19.48)	8.13 (7.68–8.61)
NLR	0.15 (0.12–18.97)	0.17 (0.14–0.20)	0.029 (0.017–0.049)
CIN2+
Sensitivity	92.73 (89.74–95.73)	87.46 (83.57–91.34)	98.26 (96.76–99.77)
Specificity	89.29 (88.67–89.92)	93.43 (92.93–93.93)	85.98 (85.27–86.68)
PPV	20.90 (18.68–23.13)	28.18 (25.18–31.17)	17.57 (15.71–19.42)
NPV	99.75 (99.65–99.86)	99.61 (99.48–99.74)	99.94 (99.88–99.99)
PLR	8.66 (8.10–9.26)	13.31 (12.19–14.54)	7.01 (6.65–7.38)
NLR	0.08 (0.054–0.12)	0.13 (0.098–0.18)	0.02 (0.008–0.048)
CIN3+
Sensitivity	93.30 (89.91–96.69)	88.94 (84.59–93.30)	99.03 (97.71–100.00)
Specificity	88.62 (87.98–89.25)	92.78 (92.26–93.30)	85.28 (84.58–86.00)
PPV	15.21 (13.24–17.18)	20.44 (17.75–23.12)	12.79 (11.16–14.42)
NPV	99.83 (99.75–99.92)	99.76 (99.65–99.86)	99.98 (99.94–100.00)
PLR	8.20 (7.67–8.76)	12.33 (11.30–13.45)	6.73 (6.40–7.08)
NLR	0.08 (0.046–0.13)	0.12 (0.08–0.18)	0.01 (0.003–0.05)

Notes: CIN1+: included CIN1 or worse; CIN2+: included CIN2 or worse; CIN3+: included CIN3 or worse.

Abbreviations: CIN, cervical intraepithelial neoplasia; HR-HPV, high-risk human papillomavirus; NLR, negative likelihood ratio; NPV, negative predictive value; PLR, positive likelihood ratio; PPV, positive predictive value; TCT, thinprep cytologic test.