【作者】 王伟；

【导师】 王渠源；

【作者基本信息】 吉林大学 ， 临床医学硕士（专业学位）， 2025， 硕士

【摘要】 目的:本研究通过对比分析HPV非相关性宫颈腺癌(Non-HPV-associated Cervical Adenocarcinoma,NHPVA)和普通型宫颈腺癌(UEA)的临床资料(年龄、孕产次、症状、体征、辅助检查等)、病理资料(术前病理、术后病理、肿瘤直径、间质浸润深度、脉管浸润、宫旁浸润、淋巴结转移、卵巢/输卵管转移、免疫组化结果)、手术治疗方法,探讨HPV非相关性宫颈腺癌临床及病理特征,提高临床医生对其认识,提升其诊断率并探讨其手术治疗方案的选择和未来其他治疗的可能性。方法:通过电子病历管理系统,收集吉林大学第二医院自2012年1月1日至2024年6月30日治疗的宫颈癌患者,基于国际宫颈腺癌分类标准对其重新分类,共收集到HPV非相关性宫颈腺癌80例,随机选取相同时期普通型宫颈腺癌患者80例,回顾性分析两组患者的临床资料(年龄、孕产次、症状、体征、辅助检查等)、病理资料(术前病理、术后病理、肿瘤直径、间质浸润深度、脉管浸润、宫旁浸润、淋巴结转移、卵巢/输卵管转移、免疫组化结果)、手术治疗方法。使用SPSS27.0对收集的相关数据信息进行处理和分析。计量资料中符合正态分布的用均数±标准差(X±S)表示,组间比较采用独立样本t检验,不满足正态分布的组件比较采用非参数检验。计数资料用率表示,组间比较采用卡方检验或者Fisher确切概率法检验。P值<0.05认为差异有统计学意义。结果:1.NHPVA平均发病年龄为52.3±9.6岁,中位年龄为52岁;UEA平均发病年龄为47.6±9.2岁,中位年龄为46.5岁,两组发病年龄存在统计学差异(P<0.05)。80例NHPVA中绝经患者41例,80例普通型宫颈腺癌中绝经患者27例,两者存在统计学差异(P<0.05)。2.NHPVA组患者最大孕次为8次,最小孕次为0次,中位孕次为2次,最大产次为5次,最小产次为0次,中位产次为1次;UEA组患者最大孕次为5次,最小孕次为0次,中位孕次为2次,最大产次为3次,最小产次为0次,中位产次为1.次。两组孕次无统计学差异(P>0.05),产次有统计学差异(P<0.05)。3.NHPVA组阴道不规则流血、阴道异常排液发生率显著高于UEA组(P<0.05),接触性出血、无明显症状发生率显著低于UEA组(P<0.05)。透明细胞癌核心症状是不规则阴道流血和腹痛腹胀,与UEA有统计学差异(P<0.05);胃型腺癌标志性症状是阴道异常排液和盆腔肿物,与UEA有统计学差异(P<0.05);子宫内膜样癌的典型症状是阴道不规则流血,与UEA有统计学差异(P<0.05)。4.NHPVA组宫颈肥大发生率显著高于UEA组,宫颈糜烂样改变发生率显著低于UEA组,均具有统计学差异(P<0.05)。5.两组的TCT阳性率无明显差异(P>0.05)。NHPVA超声检查中宫颈异常回声的发生率显著低于UEA,盆腔或附件区肿物发生率显著高于UEA,均具有统计学意义(P<0.05)。NHPVA组CA125及CA199阳性率显著高于UEA组,且具有统计学意义(P<0.05)。6.NHPVA组活检病理与术后病理诊断一致性率显著低于UEA组,差异具有统计学意义(P<0.05)。在NHPVA组中,透明细胞癌检出率较高,超过50%,胃型腺癌、子宫内膜样癌、浆液性癌检出率均较低。7.NHPVA组在肿瘤直径≥4cm的比例、宫颈深层浸润率、淋巴脉管间隙浸润率、宫体受累率、淋巴结转移率、输卵管卵巢转移率均较UEA组更高,具有统计学差异(P<0.05)。8.NHPVA组患者I期占比显著低于UEA组,III期占比显著高于UEA组,均有统计学差异(P<0.05)。两者在II期和IV期无明显统计学差异(P>0.05)。9.NHPVA组P16阳性率显著低于UEA组,ER和PR阳性率显著高于UEA组,具有统计学差异(P<0.05)。结论:1.NHPVA年龄和绝经与UEA存在显著统计学差异,因此临床上对于高龄、已绝经且HPV阴性的宫颈病变患者,需高度警惕NHPVA(尤其是胃型腺癌)可能性,建议进一步完善检验检查明确诊断。2.NHPVA活检病理与术后病理一致率低(32.9%),建议对疑似病理增加免疫组化套餐,必要时多次活检、宫颈穿刺活检或者诊断性锥切以提高诊断率。3.HPV非相关宫颈癌相较于宫颈普通型腺癌表现出更高的侵袭性浸润,更易远处转移,这一点在宫颈胃型腺癌上尤其显著。对不同病理类型的手术方案和手术范围进行更细致准确的选择,进行个体化手术治疗。更多还原

【Abstract】 Objective:This study aims to compare and analyze the clinical data(age,parity,symptoms,signs,auxiliary examinations,etc.),pathological data(preoperative pathology,postoperative pathology,tumor diameter,depth of stromal invasion,vascular invasion,parametrial invasion,lymph node metastasis,ovarian/tubal metastasis,immunohistochemical results),and surgical treatment methods of Non-HPV-associated cervical adenocarcinoma(Non-HPV-associated Cervical Adenocarcinoma,NHPVA)and usual-type endocervical adenocarcinoma(Usual-Type Endocervical Adenocarcinoma,UEA)to explore the clinical and pathological characteristics of HPV non-associated cervical adenocarcinoma,enhance clinicians’ understanding of it,improve its diagnostic efficiency,and explore the possibility of optimizing its surgical treatment.Methods:Cervical adenocarcinoma cases treated at the Second Hospital of Jilin University from January 1,2012,to June 30,2024,were reclassified using the International Endocervical Adenocarcinoma Criteria(IECC).Eighty NHPVA cases and 80 randomly selected UEA cases were included.Retrospective analysis of clinical and pathological data was performed.Statistical analysis was conducted using SPSS 27.0.Normally distributed continuous variables were expressed as mean ± standard deviation(X±SD)and compared using independent samples t-test;non-normally distributed variables were analyzed with non-parametric tests.Categorical variables were compared using Chi-square or Fisher’s exact tests.A P-value <0.05 was considered statistically significant.Results:1.The average age of onset of NHPVA was 52.3 ± 9.6 years,with a median age of 52 years;the average age of onset of UEA was 47.6 ± 9.2 years,with a median age of 46.5 years.There was a statistically significant difference in the age of onset between the two groups(P<0.05).Among the 80 cases of NHPVA,41 were postmenopausal patients,and among the 80 cases of usual-type endocervical adenocarcinoma,27 were postmenopausal patients.There was a statistically significant difference between the two groups(P<0.05).2.In the NHPVA group,the maximum number of pregnancies was 8,the minimum number of pregnancies was 0,the median number of pregnancies was 2,the maximum number of parities was 5,the minimum number of parities was 0,and the median number of parities was 1.In the UEA group,the maximum number of pregnancies was 5,the minimum number of pregnancies was 0,the median number of pregnancies was 2,the maximum number of parities was 3,the minimum number of parities was 0,and the median number of parities was 1.There was no statistically significant difference in gestational frequency between the two groups(P>0.05),but there was a statistically significant difference in parity(P<0.05).3.The incidences of irregular vaginal bleeding and abnormal vaginal discharge in the NHPVA group were significantly higher than those in the UEA group(P<0.05),and the incidence of contact bleeding and no obvious symptoms was significantly lower than that in the UEA group(P<0.05).The core symptoms of clear cell carcinoma were irregular vaginal bleeding and abdominal pain and bloating,which were statistically different from UEA(P<0.05),the hallmark symptoms of gastric adenocarcinoma were abnormal vaginal discharge and pelvic mass,which were statistically different from UEA(P<0.05),and the typical symptoms of endometrioid carcinoma were irregular vaginal bleeding,which was statistically different from UEA(P<0.05).4.The incidence of cervical hypertrophy in the NHPVA group was significantly higher than that in the UEA group,and the incidence of cervical erosion-like changes was significantly lower than that in the UEA group,both of which were statistically different(P<0.05).5.There was no significant difference in the positive rate of TCT between the two groups(P>0.05).The incidence of cervical echo in NHPVA ultrasonography was significantly lower than that of UEA,and the incidence of pelvic or adnexal mass was significantly higher than that of UEA,both of which were statistically significant(P<0.05).The positive rates of CA125 and CA199 in the NHPVA group were significantly higher than those in the UEA group,and were statistically significant(P<0.05).6.The consistency rate between biopsy pathology and postoperative pathological diagnosis in the NHPVA group was significantly lower than that in the UEA group,and the difference was statistically significant(P<0.05).In the NHPVA group,the detection rate of clear cell carcinoma was higher,more than 50%,and the detection rate of gastric adenocarcinoma,endometrioid carcinoma,and serous carcinoma was low.7.The proportion of tumor diameter ≥4cm,deep cervical invasion rate,lymphatic vascular space invasion rate,uterine body involvement rate,lymph node metastasis rate,and tubo-ovarian metastasis rate in the NHPVA group were higher than those in the UEA group,and there were statistically significant differences(P<0.05).8.The proportion of stage I patients in the NHPVA group was significantly lower than that in the UEA group,and the proportion of stage III was significantly higher than that in the UEA group,both of which were statistically different(P<0.05).There was no significant difference between the two in stage II and IV(P>0.05).9.The positive rate of P16 in the NHPVA group was significantly lower than that in the UEA group,and the positive rates of ER and PR were significantly higher than those in the UEA group,with a statistical difference(P<0.05)Conclusion:1.Significant statistical differences exist between NHPVA(non-HPV-associated)age,menopausal status,and UEA.Therefore,clinicians should maintain high suspicion for NHPVA(particularly gastric-type adenocarcinoma)in elderly,postmenopausal patients with HPV-negative cervical lesions.It is recommended to perform comprehensive examinations to confirm diagnosis.2.NHPVA shows low concordance rate(32.9%)between biopsy pathology and postoperative pathology.For suspected cases,it is advised to enhance immunohistochemical testing panels,and consider multiple biopsies,cervical puncture biopsies,or diagnostic conization when necessary to improve diagnostic accuracy.3.Compared to conventional cervical adenocarcinoma,HPV-independent cervical cancer demonstrates more aggressive infiltration patterns and higher propensity for distant metastasis,especially in cervical gastric-type adenocarcinoma.Surgical strategies should be individualized through meticulous selection of operative approaches and precise determination of surgical margins based on specific pathological subtypes.更多还原