The Triage Effectiveness of an Extended High-Risk Human Papillomavirus Genotyping Assay for Women with Cytology Showing Atypical Squamous Cells of Undetermined Significance in China

Figures & data

Figure 1 The flowchart of this study.

Abbreviations: HR-HPV, HR-HPV, high-risk human papillomavirus, including types HPV-16, −18, −31, −33, −35, −39, −45, −51, −52, −56, −58, −59, −66, −68; ASC-US, atypical squamous cells of undetermined significance; CIN1/2/3, cervical intraepithelial neoplasia grade 1/2/3; ECC, endocervical curettage.

Table 1 Characteristics for Women with Cytology Showing ASC-US (N=2393)

Characteristics	No. of Women	Mean (x±s) or Prevalence (%)
Age	2393	38.42±10.28
21–30	605	26.33±2.88
31–40	835	35.57±2.88
41–50	671	44.80±2.71
51–65	255	56.18±4.25
>65	27	70.56±3.52
Degree of education
Uneducated	217	9.1
Primary school education	373	15.6
Middle school education	1188	49.6
≥Higher education	615	25.7
Drinking history
Yes-At least 2 times a week	96	4.0
Yes- Less than 2 times a week	660	27.6
No	1637	68.4
Smoking history
Yes-At least 2 times a week	49	2.0
Yes-Less than 2 times a week	12	0.5
No	2332	97.5
Times of pregnancy
≤2	1538	64.3
>2	855	35.7
Times of childbirth
≤2	2041	85.3
>2	352	14.7
HR-HPV infection
Positive	1139	47.6
Negative	1254	52.4

Abbreviations: ASC-US, atypical squamous cells of undetermined significance; HR-HPV, high-risk human papillomavirus, including types HPV-16, −18, −31, −33, −35, −39, −45, −51, −52, −56, −58, −59, −66, −68.

Table 2 Prevalence of Different HR-HPV Genotypes in Women with ASC-US (N=2393)

Variate	Positive n (%)	Negative n (%)
Age^a
21–30	310 (51.2%)	295 (48.8%)
31–40	392 (46.9%)	443 (53.1%)
41–50	314 (46.8%)	357 (53.2%)
51–65	112 (43.9%)	143 (56.1%)
>65	11 (40.7%)	16 (59.3%)
HR-HPV	1139 (47.6%)	1254 (52.4%)
HPV16	226 (9.4%)	2167 (90.6%)
HPV18	88 (3.7%)	2305 (96.3%)
HPV31	64 (2.7%)	2329 (97.3%)
HPV33	71 (3.0%)	2322 (97.0%)
HPV35	26 (1.1%)	2367 (98.9%)
HPV39	69 (2.9%)	2324 (97.1%)
HPV45	33 (1.4%)	2360 (98.6%)
HPV51	103 (4.3%)	2290 (95.7%)
HPV52	329 (13.7%)	2064 (86.3%)
HPV56	81 (3.4%)	2312 (96.6%)
HPV58	201 (8.4%)	2192 (91.6%)
HPV59	62 (2.6%)	2331 (97.4%)
HPV66	60 (2.5%)	2333 (97.5%)
HPV68	67 (2.8%)	2326 (97.2%)

Notes: ^aOnly consider the prevalence of HR-HPV.

Abbreviations: HR-HPV, high-risk human papillomavirus, including types HPV-16, −18, −31, −33, −35, −39, −45, −51, −52, −56, −58, −59, −66, −68. ASC-US, atypical squamous cells of undetermined significance.

Table 3 Distribution of Different HR-HPV Genotypes Model According to Histologic Diagnosis in Women with ASC-US. (N=2393)

HR-HPV Types Model	Histologic Diagnosis
	Normal/CIN1 N=2151, n (%)	CIN2+ N=242, n (%)	P-value
HR-HPV	909 (42.3%)	230 (95.0%)	<0.001
HPV16	110 (5.1%)	116 (47.9%)	<0.001
HPV18	71 (3.3%)	17 (7.0%)	0.004
HPV31	51 (2.4%)	13 (5.4%)	0.006
HPV33	57 (2.6%)	14 (5.8%)	0.006
HPV35	23 (1.1%)	3 (1.2%)	1.000
HPV39	64 (3.0%)	5 (2.1%)	0.423
HPV45	29 (1.3%)	4 (1.7%)	0.925
HPV51	98 (4.6%)	5 (2.1%)	0.070
HPV52	284 (13.2%)	45 (18.6%)	0.021
HPV56	75 (3.5%)	6 (2.5%)	0.411
HPV58	150 (7.0%)	51 (21.1%)	<0.001
HPV59	56 (2.6%)	6 (2.5%)	0.908
HPV66	58 (2.7%)	2 (0.8%)	0.078
HPV68	65 (3.0%)	2 (0.8%)	0.050
HPV16/18^a	178 (8.3%)	131 (54.1%)	<0.001
HPV16/18/58^b	314 (14.6%)	174 (71.9%)	<0.001
HPV16/18/52/58^c	568 (26.4%)	203 (83.9%)	<0.001
HPV16/18/33/52/58^d	611 (28.4%)	212 (87.6%)	<0.001
HPV16/18/31/33/52/58^e	645 (30.0%)	221 (91.3%)	<0.001

Notes: ^aWomen with HPV16 and/or HPV18 infection; ^ball women with any positive of HPV16, HPV18, and HPV58; ^call women with any positive of HPV16, HPV18, HPV52 and HPV58; ^dall women with any positive of HPV16, HPV18, HPV33, HPV52 and HPV58; ^eall women with any positive of HPV16, HPV18, HPV31, HPV33, HPV52 and HPV58.

Abbreviations: HR-HPV, high-risk human papillomavirus, including types HPV-16, −18, −31, −33, −35, −39, −45, −51, −52, −56, −58, −59, −66, −68; CIN, cervical intraepithelial neoplasia; CIN2+, cervical intraepithelial neoplasia grade 2 or worse; ASC-US, atypical squamous cells of undetermined significance.

Table 4 Risk of CIN2+ Stratified by HR-HPV Genotype in Women with ASC-US (N=2393)

HR-HPV Types	No. of Women	OR	ORadjust (95% CI)^a	P-value
Age
21–30	605	1 (R)	1 (R)
31–40	835	1.62 (1.10–2.38)	2.01 (1.28–3.17)	0.003
41–50	671	2.16 (1.47–3.18)	2.68 (1.70–4.22)	<0.001
51–65	255	1.17 (0.67–2.04)	1.56 (0.82–2.96)	0.176
>65	27	1.10 (0.25–4.80)	1.29 (0.17–9.77)	0.805
HR-HPV
Negative	1254	1 (R)	1 (R)
Positive	1139	26.19 (14.57–47.08)	16.18 (7.87–33.24)	<0.001
HPV16
Negative	2167	1 (R)	1 (R)
Positive	226	17.08 (12.44–23.45)	26.38 (18.28–38.09)	<0.001
HPV18
Negative	2305	1 (R)	1 (R)
Positive	88	2.21 (1.28–3.82)	4.44 (2.34–8.42)	<0.001
HPV31
Negative	2329	1 (R)	1 (R)
Positive	64	2.34 (1.25–4.36)	2.97 (1.37–6.45)	0.006
HPV33
Negative	2322	1 (R)	1 (R)
Positive	71	2.26 (1.24–4.11)	3.38 (1.63–7.00)	0.001
HPV35
Negative	2367	1 (R)	1 (R)
Positive	26	1.16 (0.35–3.90)	2.09 (0.58–7.55)	0.262
HPV39
Negative	2324	1 (R)	1 (R)
Positive	69	0.69 (0.27–1.73)	1.23 (0.43–3.52)	0.699
HPV45
Negative	2360	1 (R)	1 (R)
Positive	33	1.23 (0.43–3.53)	1.32 (0.41–4.31)	0.642
HPV51
Negative	2290	1 (R)	1 (R)
Positive	103	0.44 (0.18–1.10)	0.53 (0.19–1.50)	0.233
HPV52
Negative	2064	1 (R)	1 (R)
Positive	329	1.50 (1.06–2.13)	2.96 (1.96–4.48)	<0.001
HPV56
Negative	2312	1 (R)	1 (R)
Positive	81	0.70 (0.30–1.63)	0.66 (0.23–1.89)	0.438
HPV58
Negative	2192	1 (R)	1 (R)
Positive	201	3.56 (2.51–5.06)	7.04 (4.59–10.78)	<0.001
HPV59
Negative	2331	1 (R)	1 (R)
Positive	62	0.95 (0.41–2.23)	0.76 (0.29–2.02)	0.582
HPV66
Negative	2333	1 (R)	1 (R)
Positive	60	0.30 (0.07–1.24)	0.14 (0.02–0.85)	0.032
HPV68
Negative	2326	1 (R)	1 (R)
Positive	67	0.27 (0.07–1.10)	0.22 (0.05–1.02)	0.053
HPV16/18^b
Negative	2084	1 (R)	1 (R)
Positive	309	13.08 (9.73–17.58)	19.34 (13.76–27.19)	<0.001
HPV16/18/58^c
Negative	1905	1 (R)	1 (R)
Positive	488	14.97 (11.04–20.30)	18.73 (13.46–26.07)	<0.001
HPV16/18/52/58^d
Negative	1622	1 (R)	1 (R)
Positive	771	14.51 (10.16–20.71)	16.99 (11.73–24.61)	<0.001
HPV16/18/33/52/58^e
Negative	1570	1 (R)	1 (R)
Positive	823	17.81 (12.02–26.40)	19.76 (13.22–29.55)	<0.001
HPV16/18/31/33/52/58^f
Negative	1527	1 (R)	1 (R)
Positive	866	24.57 (15.56–38.81)	15.08 (7.61–29.86)	<0.001

Notes: ^aOR values were adjusted for age, education level, smoking, drinking, number of pregnancy, and number of childbirth; ^bwomen with HPV16 and/or HPV18 infection directly referred to colposcopy and biopsy; ^call women with any positive of HPV16, HPV18, and HPV58 were directly referred to colposcopy and biopsy; ^dall women with any positive of HPV16, HPV18, HPV52 and HPV58 were directly referred to colposcopy and biopsy; ^eall women with any positive of HPV16, HPV18, HPV33, HPV52 and HPV58 were directly referred to colposcopy and biopsy; ^fall women with any positive of HPV16, HPV18, HPV31, HPV33, HPV52 and HPV58 were directly referred to colposcopy and biopsy.

Abbreviations: OR, odds ratio; ASC-US, atypical squamous cells of undetermined significance; HR-HPV, high-risk human papillomavirus, including types HPV-16, −18, −31, −33, −35, −39, −45, −51, −52, −56, −58, −59, −66, −68; R, reference.

Table 5 The Effect of Different HR-HPV Genotypes Model in Triaging Women with ASC-US. (N=2393)

HR-HPV Genotypes Model	Sensitivity % (95% CI)	Specificity % (95% CI)	PPV % (95% CI)	NPV % (95% CI)	Referral Rate^a % (n/N)
HR-HPV^b	95.0 (92.3–97.8)	57.7 (55.7–59.8)	20.2 (18.1–22.7)	99.0 (98.5–99.6)	47.6 (1139/2393)
HPV16/18^c	54.1 (47.9–60.4)	91.7 (90.6–92.9)	42.4 (36.5–47.5)	94.7 (93.3–95.3)	12.9 (309/2393)
HPV16/18/58^d	71.9 (66.2–77.6)	85.4 (83.9–86.9)	35.7 (31.1–39.6)	96.4 (95.1–96.9)	20.4 (488/2393)
HPV16/18/52/58^e	83.9 (79.3–88.5)	73.6 (71.7–75.5)	26.3 (22.9–29.1)	97.6 (96.2–97.8)	32.2 (771/2393)
HPV16/18/33/52/58^f	87.6 (83.5–91.8)	71.6 (69.7–73.5)	25.8 (22.5–28.5)	98.1 (96.7–98.2)	34.4 (823/2393)
HPV16/18/31/33/52/58^g	91.3 (87.8–94.9)	70.0 (68.1–72.0)	25.5 (22.4–28.2)	98.6 (97.3–98.7)	36.2 (866/2393)

Notes: ^aThe rate of referred to colposcopy in ASC-US women; ^ball women with any positive of HPV16, HPV18, HPV 31, HPV 33, HPV 35, HPV 39, HPV 45, HPV 51, HPV 52, HPV 56, HPV 58, HPV 59, HPV 66 and HPV68 were directly referred to colposcopy and biopsy; ^cwomen with HPV16 and/or HPV18 infection directly referred to colposcopy and biopsy; ^dall women with any positive of HPV16, HPV18, and HPV58 were directly referred to colposcopy and biopsy; ^eall women with any positive of HPV16, HPV18, HPV52 and HPV58 were directly referred to colposcopy and biopsy; ^fall women with any positive of HPV16, HPV18, HPV33, HPV52 and HPV58 were directly referred to colposcopy and biopsy; ^gall women with any positive of HPV16, HPV18, HPV31, HPV33, HPV52 and HPV58 were directly referred to colposcopy and biopsy.

Abbreviations: HR-HPV, high-risk human papillomavirus, including types HPV-16, −18, −31, −33, −35, −39, −45, −51, −52, −56, −58, −59, −66, −68; PPV, positive predictive value; NPV, negative predictive value.