| Background and Purpose:Cervical cancer(CC)is the fourth most frequently diagnosed cancer and the fourth leading cause of cancer death in women.Human papilloma virus(HPV)has been confirmed as the primary pathogen in cervical cancer development,especially for high-risk genotypes.The HPV DNA was detected in majority of cervical cancer tissue specimens,however,a small number of HPV tests for cervical cancer are always negative regardless of the test method.Some studies found that HPV negative cervical cancer was associated with poor prognosis,and diagnosed at advanced stage,while some previous studies also failed to figure out the relationship between cervical cancer prognosis and the absence of HPV DNA,arguing that the two were not statistically significant.However,whether HR HPV infection affects the prognosis of cervical cancer is still controversial in domestic and foreign researches.HPV 16 and HPV18 are the most critical genotypes in the development of cervical cancer,accounting for about 70%of all cervical cancers.Several studies exploring the effect of genotype on the prognosis of cervical cancer have not yet reached a consistent conclusion.The purpose of this retrospective study was to analyze the clinicopathological features of cervical cancer and the prognostic value of pre-treatment HPV DNA status,as well as the effect of HPV 16 and HPV 18 positivity on prognosis.Method:This study was a single-center retrospective cohort study.Cervical cancer patients who had HPV infection before treatment at Qilu Hospital of Shandong University from January 2016 to December 2019 were collected.The International Federation of Gynecology and Obstetrics(FIGO 2018)staging system was used.Patient age,FIGO stage,tumor histological grade,and pathological variables were retrieved from medical records.Based on HPV status,the patients were divided into 2 study groups:HPV positive and HPV negative.In order to explore whether different genotypes of HPV have an impact on the prognosis,we further selected cervical cancer patients with single infection of HPV 16 and HPV18 in the HPV positive group.The clinicopathologic features between HPV negative and HPV positive cervical cancer patients,HPV 16 positive and HPV 18 positive cervical cancer patients were respectively compared.The primary endpoint was overall survival(OS),and the secondary endpoint was progression-free survival(PFS).All tests were two sides,and the significance level was determined at 0.05.Hazard ratios and 95%confidence intervals were calculated using the Wald test for risk estimates.Multivariate Cox models incorporated all variables that were statistically significant in univariate models.Result:1.Clinical characteristics between HPV negative and HPV positive cervical cancer patients:This study collected 1,225 cervical cancer patients,and 55 patients were excluded due to loss of follow-up or significant data absence.Finally,1,170 patients were included in the analysis.There were 904 patients(77.3%)with International Federation of Gynecology and Obstetrics(FIGO)stage 1,98 patients(8.4%)with stage Ⅱ,and 168 patients(14.4%)with stage III.Patients were divided into groups according to HPV infectious status.Of the 1,170 patients,88(7.5%)patients were classified as HPV-negative cervical cancer and 1,082(92.5%)as HPV-positive cervical cancer.Compared with HPV-positive patients,HPV-negative patients were older(47.73±9.28 years vs.45.04± 10.36years;P=0.018)and more commonly of the adenocarcinoma(50%vs.10.1%,P<0.001)and deeper cervical stromal infiltration(with more than 1/3 depth of cervical infiltration,61.4%vs.49.4%,P=0.003).The tumor diameter of HPV-negative tumors was larger than HPV-positive tumors(>4cm,31.8%vs.9.2%,P<0.001).Basic clinical features and pathological values have no difference between the groups:FIGO stage(P=0.416),LVSI(P=0.186),histological grade(P=0.285),and postoperative adjuvant therapy(P=0.12).No statistical differences were seen between the two groups in pregnancy(P=0.755)and parturition(P=0.723).2.Survival analysis between HPV negative and HPV positive cervical cancer patients:We found 74(6.3%)cervical cancer patients died during the follow-up period,the median follow-up was 46(range,1-77)months.The 3-year survival rate of HPV-negative and positive group was 89.6%vs.95.3%(P=0.034),and the 5-year survival rate was 85.8%vs.93.3%(P=0.009).However,the DFS between the two groups has no difference.The OS of HPV-negative cervical cancer patients was significantly worse than that of HPV-positive cervical cancer patients(P=0.006).The existence of HR-HPV DNA was linked to better survival.However,on multivariate analysis,only FIGO stage,depth of stromal infiltration,and the histopathological type remained were independent risk factors for the prognosis of patients with cervical cancer.3.Clinical characteristics between HPV16 and HPV18 cervical cancer patients:Among HPV-positive patients,there were 562 patients with single HPV 16 infection and 55 patients with single HPV18 infection.A total of 36 deaths(5.8%)were observed in the two groups during the follow-up period.No statistical differences were observed between the two groups in age,FIGO stage,histological differentiation,tumor size,and depth of stromal infiltration.There were significant statistical differences in pathological type(P<0.001),LVSI(P=0.048)and adjuvant therapy(P=0.031).The proportion of adenocarcinoma in HPV18 positive cervical cancer was higher than that of HPV16 positive patients(43.6%vs.7.1%,P<0.001),HPV16 positive cervical cancer was mainly squamous cell carcinoma(91.6%).The proportion of LVSI positivity was lower in HPV-18 positive cervical cancer than that in HPV-18 positive(40.9%vs.27.3%,P=0.048).4.Survival analysis between HPV16 and HPV18 cervical cancer patients:We found 36(5.8%)cervical cancer patients died during the follow-up period.The median follow-up was 46(range,1-77)months.The 3-year survival rate of HPV16 and HPV18 group was 96.4%vs.87.3%(P=0.005).Survival analysis showed that HPV18 positive cervical cancer patients had worse OS(P=0.013)and PFS(P=0.007)than HPV16 patients.On multivariate analysis,HPV-18 remained connected with worse survival than HPV-16(P<0.001),Tumors harboring HPV-16 infection exhibited a better overall survival.The depth of stromal invasion(P<0.05)and FIGO stage(P<0.001)were also independent prognostic factors.FIGO III stage(P=0.001),HPV18(P<0.001)and depth of cervical stromal invasion(P=0.015)were independent risk factors of PFS.Conclusion:1.The proportion of adenocarcinoma in HPV negative cervical cancer was significantly higher than that in HPV positive cervical cancer patients,and the tumor diameter was larger and the depth of cervical stromal infiltration was deeper.The prognosis of HPV-positive patients is better than that of HPV-negative patients,but it is not an independent risk factor affecting the prognosis of cervical cancer patients.2.FIGO stage and the depth of cervical stromal invasion are independent risk factors for prognosis of cervical cancer.The more advanced the stage and the deeper the interstitial infiltration,the worse the prognosis.3.HPV18 positive patients with cervical adenocarcinoma ratio is higher than new HPV 16 patients,and worse prognosis.HPV genotype is an independent risk factor affecting the prognosis.HPV status before treatment may be a prognostic marker,which has a certain guiding effect on the prognosis and treatment of cervical cancer patients. |
PDF Full Text Request