Effect of P16 and Ki67 expression and viral load detection on outcome of cervical lesions in woman of childbearing age with cervical intraepithelial neoplasia grade Ⅱ complicated with high-risk human papillomavirus infection

doi:10.3877/cma.j.issn.1674-0785.2023.03.007

Abstract

Abstract:

Objective

To investigate the expression of P16 and Ki67 in female patients of childbearing age with cervical intraepithelial neoplasia grade Ⅱ (CINⅡ) complicated with high-risk human papillomavirus (HR-HPV) infection, and to analyze the effect of both and HR-HPV viral load on the outcome of CINⅡ.

Methods

One hundred and three female patients of childbearing age with CINⅡ complicated with HR-HPV infection treated at our hospital from January 2020 to January 2021 were selected as an observation group, and 51 female patients of childbearing age with CINⅡ without HR-HPV infection treated at the same hospital during the same period were selected as a control group. All patients in the observation group received surgical treatment and were followed up for 1 year, and according to the outcome of CINⅡ at the 1-year follow-up, they were divided into a regression group, a persistent group, and a progression group. The baseline data were collected via a questionnaire, relevant laboratory indexes were detected, and the baseline data and laboratory indexes of patients with different outcomes of cervical lesions were compared. The effect of expression of P16 and Ki67 and HR-HPV viral load on the outcomes of CINⅡ was analyzed.

Results

The 103 patients with CINⅡ complicated with HR-HPV infection were followed up for 1 year. The lesions subsided in 66, continued in 21, and progressed in 16 cases. The positive expression rates of P16 and Ki67 in the observation group were significantly higher than those in the control group (P＜0.05). The positive expression rates of P16 and Ki67 were the highest in the progression group, followed by the persistent group, and the lowest in the regression group. HR-HPV load was the highest in the progression group, followed by the persistent group, and the lowest in the regression group, which differed significantly among the three groups (P＜0.05). Ordered regression analysis showed that, with the increase of P16 and Ki67 expression and HR-HPV load, the possibility of persistency and aggravation of cervical lesions was 6.987, 4.928, and 1.009 times higher, respectively (P＜0.05). Decision curve analysis showed that, in the range of high-risk threshold of 0~1.0, the net benefit rate of combined P16 and Ki67 expression and HR-HPV load for predicting cervical lesion persistence and lesion progression in patients with CINⅡ was always >0 and had clinical significance.

Conclusion

P16 and Ki67 are abnormally expressed in female patients of childbearing age with CINⅡ complicated with HR-HPV infection, and P16 and Ki67 expression and HR-HPV load may affect the outcome of patients with cervical lesions.

Key words: Cervical intraepithelial neoplasia, High risk-human papillomavirus, P16, Ki67, Viral load

Mi Li, huajuan Qiu, Yanqin Ji, Minghui Zhou. Effect of P16 and Ki67 expression and viral load detection on outcome of cervical lesions in woman of childbearing age with cervical intraepithelial neoplasia grade Ⅱ complicated with high-risk human papillomavirus infection[J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(03): 272-278.

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Figures/Tables 7

项目	观察组（n=103）	对照组（n=51）	统计值	P值
年龄（ $x ¯$ ±s，岁）	37.28±2.71	37.14±2.52	t=0.309	0.758
体重指数（ $x ¯$ ±s，kg/m²）	21.27±1.37	21.17±1.18	t=0.401	0.689
产次（ $x ¯$ ±s，次）	2.67±0.61	2.61±0.53	t=0.599	0.550
孕次（ $x ¯$ ±s，次）	3.15±0.84	3.08±0.79	t=0.496	0.621
性伴侣数［n（%）］			χ²=1.937	0.164
1个	84（81.55）	46（90.20）
＞1个	19（18.45）	5（9.80）
吸烟史［n（%）］			χ²=0.180	0.672
有	19（18.45）	8（15.69）
无	84（81.55）	43（84.31）
大量饮酒史［n（%）］			χ²=1.250	0.264
有	20（19.42）	7（13.73）
无	83（80.58）	83（80.58）
手术方式［n（%）］			χ²=0.582	0.446
宫颈环形电切术	45（43.69）	19（37.25）
宫颈冷刀锥切术	58（56.31）	32（62.75）
P16［n（%）］			Z=3.017	0.003
（-）	29（28.16）	27（52.94）
（+）	42（40.78）	16（31.37）
（++）	19（18.45）	5（9.80）
（+++）	13（12.62）	3（5.88）
Ki67［n（%）］			Z=2.287	0.022
（-）	25（24.27）	24（47.06）
（+）	46（44.66）	15（29.41）
（++）	21（20.39）	8（15.69）
（+++）	11（10.68）	4（7.84）

项目	观察组（n=103）	对照组（n=51）	统计值	P值
年龄（ $x ¯$ ±s，岁）	37.28±2.71	37.14±2.52	t=0.309	0.758
体重指数（ $x ¯$ ±s，kg/m²）	21.27±1.37	21.17±1.18	t=0.401	0.689
产次（ $x ¯$ ±s，次）	2.67±0.61	2.61±0.53	t=0.599	0.550
孕次（ $x ¯$ ±s，次）	3.15±0.84	3.08±0.79	t=0.496	0.621
性伴侣数［n（%）］			χ²=1.937	0.164
1个	84（81.55）	46（90.20）
＞1个	19（18.45）	5（9.80）
吸烟史［n（%）］			χ²=0.180	0.672
有	19（18.45）	8（15.69）
无	84（81.55）	43（84.31）
大量饮酒史［n（%）］			χ²=1.250	0.264
有	20（19.42）	7（13.73）
无	83（80.58）	83（80.58）
手术方式［n（%）］			χ²=0.582	0.446
宫颈环形电切术	45（43.69）	19（37.25）
宫颈冷刀锥切术	58（56.31）	32（62.75）
P16［n（%）］			Z=3.017	0.003
（-）	29（28.16）	27（52.94）
（+）	42（40.78）	16（31.37）
（++）	19（18.45）	5（9.80）
（+++）	13（12.62）	3（5.88）
Ki67［n（%）］			Z=2.287	0.022
（-）	25（24.27）	24（47.06）
（+）	46（44.66）	15（29.41）
（++）	21（20.39）	8（15.69）
（+++）	11（10.68）	4（7.84）

项目	病变消退组（n=66）	病变持续组（n=21）	病变进展组（n=16）	统计值	P值
年龄（ $x ¯$ ±s，岁）	31.16±2.67	31.33±2.75	31.68±2.95	F=0.239	0.788
体重指数（ $x ¯$ ±s，kg/m²）	21.26±1.33	21.12±1.25	21.54±1.42	F=0.465	0.629
产次（ $x ¯$ ±s，次）	2.64±0.58	2.68±0.64	2.75±0.72	F=0.214	0.808
孕次（ $x ¯$ ±s，次）	3.12±0.81	3.18±0.88	3.24±0.93	F=0.146	0.864
性伴侣数［n（%）］				χ²=4.291^a	0.117^a
1个	57（86.36）	17（80.95）	10（62.50）
＞1个	9（13.64）	4（19.05）	6（37.50）
吸烟史［n（%）］				χ²=1.297^a	0.523^a
有	10（15.15）	5（23.81）	4（25.00）
无	56（84.85）	16（76.19）	12（75.00）
大量饮酒史［n（%）］				χ²=3.819^a	0.148^a
有	9（13.64）	6（28.57）	5（31.25）
无	57（86.36）	15（71.43）	11（68.75）
手术方式［n（%）］				χ²=0.308	0.857
宫颈环形电切术	28（42.42）	9（42.86）	8（50.00）
宫颈冷刀锥切术	38（57.58）	12（57.14）	8（50.00）

项目	病变消退组（n=66）	病变持续组（n=21）	病变进展组（n=16）	统计值	P值
年龄（ $x ¯$ ±s，岁）	31.16±2.67	31.33±2.75	31.68±2.95	F=0.239	0.788
体重指数（ $x ¯$ ±s，kg/m²）	21.26±1.33	21.12±1.25	21.54±1.42	F=0.465	0.629
产次（ $x ¯$ ±s，次）	2.64±0.58	2.68±0.64	2.75±0.72	F=0.214	0.808
孕次（ $x ¯$ ±s，次）	3.12±0.81	3.18±0.88	3.24±0.93	F=0.146	0.864
性伴侣数［n（%）］				χ²=4.291^a	0.117^a
1个	57（86.36）	17（80.95）	10（62.50）
＞1个	9（13.64）	4（19.05）	6（37.50）
吸烟史［n（%）］				χ²=1.297^a	0.523^a
有	10（15.15）	5（23.81）	4（25.00）
无	56（84.85）	16（76.19）	12（75.00）
大量饮酒史［n（%）］				χ²=3.819^a	0.148^a
有	9（13.64）	6（28.57）	5（31.25）
无	57（86.36）	15（71.43）	11（68.75）
手术方式［n（%）］				χ²=0.308	0.857
宫颈环形电切术	28（42.42）	9（42.86）	8（50.00）
宫颈冷刀锥切术	38（57.58）	12（57.14）	8（50.00）

项目	病变消退组（n=66）	病变持续组（n=21）	病变进展组（n=16）	统计值	P值
P16［n（%）］				Z=27.736	＜0.001
（-）	27（40.91）	2（9.52）^a	2（12.50）^a
（+）	31（46.97）	9（42.86）^a	2（12.50）^a
（++）	8（12.12）	7（33.33）^a	5（31.25）^a
（+++）	0（0）	3（14.29）^a	7（43.75）^a
Ki67［n（%）］				Z=33.192	＜0.001
（-）	23（34.85）	2（9.52）^a	1（6.25）^a
（+）	37（56.06）	6（28.57）^a	3（18.75）^a
（++）	5（7.58）	9（42.86）^a	6（37.50）^a
（+++）	1（1.52）	4（19.05）^a	6（37.50）^a
HR-HPV载量（ $x ¯$ ±s，RLU/CO）	345.56±75.82	412.36±95.63^a	487.81±104.03^ab	F=19.895	＜0.001

项目	病变消退组（n=66）	病变持续组（n=21）	病变进展组（n=16）	统计值	P值
P16［n（%）］				Z=27.736	＜0.001
（-）	27（40.91）	2（9.52）^a	2（12.50）^a
（+）	31（46.97）	9（42.86）^a	2（12.50）^a
（++）	8（12.12）	7（33.33）^a	5（31.25）^a
（+++）	0（0）	3（14.29）^a	7（43.75）^a
Ki67［n（%）］				Z=33.192	＜0.001
（-）	23（34.85）	2（9.52）^a	1（6.25）^a
（+）	37（56.06）	6（28.57）^a	3（18.75）^a
（++）	5（7.58）	9（42.86）^a	6（37.50）^a
（+++）	1（1.52）	4（19.05）^a	6（37.50）^a
HR-HPV载量（ $x ¯$ ±s，RLU/CO）	345.56±75.82	412.36±95.63^a	487.81±104.03^ab	F=19.895	＜0.001

相关因素	β值	标准误	Wald χ²值	P值	OR值	95%CI
阈值					-	-
病变持续	12.398	1.981	39.169	＜0.001
病变进展	15.309	2.388	41.108	＜0.001
位置
P16	1.738	0.345	25.375	＜0.001	5.686	2.892~11.149
Ki67	1.732	0.370	21.900	＜0.001	5.652	2.737~11.681
HR-HPV载量	0.011	0.003	10.475	0.001	1.011	1.004~1.017

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