A study on the correlation between HPV DNA and IHC P16 expression in cervical lesions

Haochen WANG; Liqing JIA; Yu YANG; Qian WANG; Chengli YU; Tian TIAN; Rui BI; Xiaoyu TU; Qianming BAI; Xiaoli ZHU; Xiaoyan ZHOU; Min REN

doi:10.19401/j.cnki.1007-3639.2025.03.006

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A study on the correlation between HPV DNA and IHC P16 expression in cervical lesions

Article | 更新时间：2025-12-31

- A study on the correlation between HPV DNA and IHC P16 expression in cervical lesions
- China Oncology Vol. 35, Issue 3, Pages: 298-308(2025)
- 作者机构：
  
  复旦大学附属肿瘤医院病理科，复旦大学医学院肿瘤学系，复旦大学病理研究所，上海 200032
- 作者简介：
- 基金信息：
  
  Shanghai Collaborative Innovation Cluster(2019CXJQ03);Special Program for Medical Innovation Research (Science and Technology Innovation Action Plan, Shanghai Municipal Science and Technology Commission)(20Z11900300)
- DOI：10.19401/j.cnki.1007-3639.2025.03.006
  CLC： R711.74
- Received：13 November 2024，
  
  Revised：2025-02-06，
  
  Published：30 March 2025
- 稿件说明：
移动端阅览
Haochen WANG, Liqing JIA, Yu YANG, et al. A study on the correlation between HPV DNA and IHC P16 expression in cervical lesions[J]. China Oncology, 2025, 35(3): 298-308.
DOI：

Haochen WANG, Liqing JIA, Yu YANG, et al. A study on the correlation between HPV DNA and IHC P16 expression in cervical lesions[J]. China Oncology, 2025, 35(3): 298-308. DOI： 10.19401/j.cnki.1007-3639.2025.03.006.

摘要

背景与目的：

人乳头状瘤病毒（human papilloma virus，HPV）感染状态在宫颈癌前病变诊断和宫颈癌分型中具有重要意义，而在宫颈病变中高危型（high-risk，HR）HPV感染通常与P16蛋白的过表达密切相关，因此在临床上对组织样本进行病理学诊断时将免疫组织化学（immunohistochemistry，IHC）检测的P16蛋白表达作为判断HPV感染情况的重要依据，但两者之间仍有部分不一致，其相关性有待深入研究，以更好地指导临床实践。

方法：

回顾性收集复旦大学附属肿瘤医院2020年1月—2023年12月进行宫颈活检或手术的618例患者的临床病理学资料（伦理批号：050432-4-2307E），采用聚合酶链反应（polymerase chain reaction，PCR）反向点杂交法检测HPV DNA多亚型，包括HR和低危型（low-risk，LR）；采用IHC检测P16蛋白水平，比较两者的一致率，评估P16表达在判断HPV感染时的灵敏度和特异度。618例宫颈病变患者中，宫颈鳞癌92例，宫颈腺癌257例，高级别鳞状上皮内病变（high-grade squamous intraepithelial lesions，HSIL）79例，低级别鳞状上皮内病变（low-grade squamous intraepithelial lesions，LSIL）105例，慢性宫颈炎85例。

结果：

在宫颈鳞癌中，HR-HPV和P16的阳性率分别为88.0%（81/92）和91.3%（84/92），一致率为90.2%（83/92），P16在判断HR-HPV感染中的灵敏度和特异度为96.3%和45.5%；在宫颈腺癌中，HR-HPV和P16的阳性率分别为54.5%（140/257）和58.8%（151/257），一致率为82.5%（212/257），P16在判断HR-HPV感染中的灵敏度和特异度为87.9%和76.1%；在HSIL中，HR-HPV和P16的阳性率分别为75.9%（60/79）和70.9%（56/79），一致率为82.2%（65/79），P16在判断HR-HPV感染中的灵敏度和特异度为85.0%和73.7%；在LSIL中，HR-HP

V和P16的阳性率分别为73.3%（77/105）和8.5%（9/105），一致率为33.3%（35/105），P16在判断HR-HPV感染中的灵敏度和特异度为10.4%和96.4%；在慢性宫颈炎中，HR-HPV和P16的阳性率分别为20.0%（17/85）和0.0%（0/85），一致率为80.0%（68/85），P16在判断HR-HPV感染中的灵敏度和特异度为0.0%和100.0%。在宫颈鳞癌、宫颈腺癌及HSIL中P16阳性与HPV16/18呈显著正相关（

=0.000），而在LSIL及慢性宫颈炎中无显著相关性（

0.05）。

结论：

在宫颈鳞癌及宫颈腺癌中，P16阳性表达与HPV DNA阳性（HPV感染）的一致率较高，尤其P16表达与HPV16/18亚型感染显著相关。HSIL中P16阳性表达可以初步反映HPV感染情况，但在LSIL及慢性宫颈炎中，P16表达难以准确地反映HPV感染情况。P16与HPV DNA检测不一致可能受感染亚型、病理学类型、样本质量等多种因素影响，实际工作中应仔细分析或用多种方法确定HPV的感染状态。

Abstract

Background and purpose:

Human papilloma virus (HPV) infection status is crucial for diagnosing cervical precancerous lesions and classifying cervical cancer. High-risk (HR) HPV is often linked to P16 protein overexpression

so P16 detection

via

immunohistochemistry (IHC) is commonly used to assess HPV infection. However

the differences between HPV status and P16 expression remains unclear. An in-depth study of the correlation between HPV and P16 is essential for clinical guidance.

Methods:

We retrospectively collected clinical and pathological data of cervical lesions from 618 patients diagnosed at the Department of Pathology

Fudan University Shanghai Cancer Center from January 2020 to December 2023 (Ethical number: 050432-4-2307E). Polymerase chain reaction (PCR) reverse dot hybridization was used to detect HPV including HR and low-risk (LR) subtypes

and immunohistochemistry was used to detect P16 for comparative analysis. Based on different clinical and pathological diagnoses

the sensitivity and specificity of P16 expression in evaluating HPV infection were evaluated. Among the 618 cases of cervical lesions

there were 92 cases of cervical squamous cell carcinoma

257 cases of cervical adenocarcinoma

79 cases of high-grade squamous intraepithelial lesions (HSIL)

105 cases of low-grade squamous intraepithelial lesions (LSIL)

and 85 cases of chronic cervical inflammati

on.

Results:

According to clinical diagnosis

the HR-HPV positive rate in cervical squamous cell carcinoma was 88.0% (81/92)

the P16 positive rate was 91.3% (84/92)

and the overall consistency rate between P16 and HPV detection was 90.2% (88/92); for HR-HPV infection

the sensitivity and specificity of P16 were 96.3% and 45.5%. The positive rate of HR-HPV in adenocarcinoma was 54.5% (140/257)

the positive rate of P16 was 58.8% (151/257)

and the overall consistency rate between P16 and HPV detection was 82.5% (212/257); for HR-HPV infection

the sensitivity and specificity of P16 were 87.9% and 76.1%. In HSIL

the HR-HPV positive rate was 75.9% (60/79)

the positive rate of P16 was 70.9% (56/79)

and the overall consistency rate between P16 and HR-HPV detection was 82.2% (65/79); for HR-HPV infection

the sensitivity and specificity of P16 were 85.0% and 73.7%. In LSIL

the HR-HPV positive rate was 73.3% (77/105)

the positive rate of P16 was 8.5% (9/105)

and the overall consistency rate between P16 and HR-HPV detection was 33.3% (35/105); for HR-HPV infection

the sensitivity and specificity of P16 were 10.4% and 96.4%. In chronic cervical inflammation

the HR-HPV positive rate was 20% (17/85)

the positive rate of P16 was 0.0% (0/85); for HR-HPV infection

the sensitivity and specificity of P16 were 0.0% and 100.0%. There was a significant positive correlation between P16 positivity and HPV16/18 in cervical squamous cell carcinoma

adenocarcinoma

and HSIL (

=0.000)

while there was no significant correlation in LSIL and chronic cervical inflammation (

0.05).

Conclusion:

In cervical squamous cell carcinoma and adenocarcinoma

the consistency of P16 expression and HPV DNA positivity are high

especially in HPV16/18 subtype. There is a good concordance between HR-HPV positivity and P16 protein overexpression. The positive expression of P16 in HSIL may initially reflect HPV infection status. However

in LSIL and chronic cervicitis

P16 expression

may not accurately correlate with HPV infection. The inconsistency between P16 and HPV DNA testing could be influenced by multiple factors

including HPV subtypes

histopathological categories

specimen quality

and technical limitations. In clinical practice

it is recommended to conduct comprehensive analysis or employ multiple diagnostic methods to confirm HPV infection status for precise evaluation.

关键词

Keywords

references

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