Objective: To investigate the natural regression and related factors of high-grade squamous intraepithelial lesion (HSIL) in the cervix of childbearing age women, and to evaluate the applicability of conservative management for future fertility needs. Methods: This study included 275 patients of reproductive age with fertility needs, who were diagnosed as HSIL by biopsy from April 30, 2015 to April 30, 2022, including 229 cases (83.3%) cervical intraepithelial neoplasia (CIN) Ⅱ and 46 cases (16.7%) CIN Ⅱ-Ⅲ. They were followed-up without immediate surgery in the First Affiliated Hospital of Nanjing Medical University. The median follow-up time was 12 months (range: 3-66 months). The regression, persistence and progression of lesions in patients with HSIL were analyzed during the follow-up period, the influencing factors related to regression and the time of regression were analyzed. Results: (1) Of the 275 HSIL patients, 213 cases (77.5%, 213/275) experienced regression of the lesion during the follow-up period. In 229 CIN Ⅱ patients, 180 cases (78.6%) regressed, 21 cases (9.2%) persisted, and 28 cases (12.2%) progressed. In 46 CIN Ⅱ-Ⅲ patients, 33 cases (71.7%) regressed, 12 cases (26.1%) persisted, and 1 case (2.2%) progressed to invasive squamous cell carcinoma stage Ⅰ a1. There was no significant difference in the regression rate between the two groups (χ²=1.03, P=0.309). (2) The average age at diagnosis, age <25 years old at diagnosis were independent influencing factor of HSIL regression in univariate analysis (all P<0.05). There was no significant difference between HSIL regression and pathological grading, the severity of screening results, human papillomavirus (HPV) genotype, colposcopy image characteristics, number of biopsies during follow-up and pregnancy experience (all P>0.05). (3) The median regression times for patients aged ≥25 years and <25 years at diagnosis were 15 and 12 months, respectively. Kaplan-Meier analysis showed that age ≥25 years at diagnosis significantly increased the median regression time compared to <25 years (χ²=6.02, P=0.014). Conclusions: For HSIL patients of childbearing age, conservative management without immediate surgical intervention is preferred if CINⅡ is fully evaluated through colposcopy examination. Age ≥25 years at diagnosis is a risk factor affecting the prognosis of HSIL patients.
Pregnancy ; Humans ; Female ; Adult ; Cervix Uteri/pathology* ; Uterine Cervical Neoplasms/pathology* ; Uterine Cervical Dysplasia/pathology* ; Biopsy ; Colposcopy/methods* ; Squamous Intraepithelial Lesions/pathology* ; Carcinoma in Situ/pathology* ; Papillomaviridae/genetics* ; Papillomavirus Infections/diagnosis* ; Squamous Intraepithelial Lesions of the Cervix/pathology*

Female ; Humans ; Uterine Cervical Neoplasms ; Uterus ; Endometrium ; Ichthyosis ; Carcinoma, Squamous Cell ; Squamous Intraepithelial Lesions

squamous cells of undetermined significance or low-grade squamous intraepithelial lesion (LSIL) were enrolled from five hospitals across Korea. Their HPV genotype, epidemiologic, and clinical data, including HPV vaccination history, were obtained. We compared the epidemiological characteristics and prevalence of HPV-16/18 genotypes between vaccinated and unvaccinated women.RESULTS: Among the 1,300 women, approximately 26% had a history of vaccination. Vaccinated patients were significantly younger, unmarried, and had a higher education level than unvaccinated women. For HPV-vaccinated individuals by vaccine dose, there was a significant younger age at vaccination initiation (p=0.025), longer duration from HPV vaccination to Pap test date (p=0.001), and lower proportion of HPV-16/18 (p=0.028) in the women with three doses. There was a significantly lower prevalence of HPV-16/18 genotypes in women who were vaccinated at least 12 months prior than in unvaccinated women (adjusted prevalence ratio [aPR]=0.51; 95% confidence interval [CI]=0.29–0.88). For women with LSIL, the prevalence of the HPV-16/18 genotypes was significantly lower in women who were vaccinated more than 12 months prior than in unvaccinated women (aPR=0.35; 95% CI=0.13–0.96).CONCLUSION: This study highlighted the status of HPV vaccination and the prevalence of HPV-16/18 genotypes among HPV-infected women with abnormal cervical cytology according to HPV vaccination. It provides preliminary information regarding the status of HPV vaccination among Korean adult women.]]>
Adult ; Atypical Squamous Cells of the Cervix ; Education ; Female ; Genotype ; Humans ; Immunization Programs ; Korea ; Papanicolaou Test ; Prevalence ; Retrospective Studies ; Single Person ; Squamous Intraepithelial Lesions of the Cervix ; Uterine Cervical Neoplasms ; Vaccination ; Vaccines

OBJECTIVE: To investigate pathologic discrepancies between colposcopy-directed biopsy (CDB) of the cervix and loop electrosurgical excision procedure (LEEP) in women with cytologic high-grade squamous intraepithelial lesions (HSILs).METHODS: We retrospectively identified 297 patients who underwent both CDB and LEEP for HSILs in cervical cytology between 2015 and 2018, and compared their pathologic results. Considering the LEEP to be the gold standard, we evaluated the diagnostic performance of CDB for identifying cervical intraepithelial neoplasia (CIN) grades 2 and 3, adenocarcinoma in situ, and cancer (HSIL+). We also performed age subgroup analyses.RESULTS: Among the study population, 90.9% (270/297) had pathologic HSIL+ using the LEEP. The diagnostic performance of CDB for identifying HSIL+ was as follows: sensitivity, 87.8%; specificity, 59.3%; balanced accuracy, 73.6%; positive predictive value, 95.6%; and negative predictive value, 32.7%. Thirty-three false negative cases of CDB included CIN2,3 (n=29) and cervical cancer (n=4). The pathologic HSIL+ rate in patients with HSIL− by CDB was 67.3% (33/49). CDB exhibited a significant difference in the diagnosis of HSIL+ compared to LEEP in all patients (p<0.001). In age subgroup analyses, age groups <35 years and 35–50 years showed good agreement with the entire data set (p=0.496 and p=0.406, respectively), while age group ≥50 years did not (p=0.036).CONCLUSION: A significant pathologic discrepancy was observed between CDB and LEEP results in women with cytologic HSILs. The diagnostic inaccuracy of CDB increased in those ≥50 years of age.
Adenocarcinoma in Situ ; Biopsy ; Cervical Intraepithelial Neoplasia ; Cervix Uteri ; Colposcopy ; Conization ; Dataset ; Diagnosis ; Early Detection of Cancer ; Female ; Humans ; Papanicolaou Test ; Retrospective Studies ; Sensitivity and Specificity ; Squamous Intraepithelial Lesions of the Cervix ; Uterine Cervical Neoplasms

OBJECTIVE: Human papillomavirus (HPV) infection is the most important risk factor for cervical cancer, which progresses from precursor lesions with no symptom if left untreated. We compared the risk of cervical dysplasia among HPV-positive Korean women based on HPV types and infection patterns. METHODS: We observed participants of a 5-year multicenter prospective cohort study, comprising HPV-positive women with either atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion of the cervix at their enrollment. Follow-ups, comprising cytology and HPV DNA testing results, were included in the final analysis. Incidence was calculated for each infection pattern (persistent infection, incidental infection, and clearance). To investigate cervical dysplasia risk, we used Cox proportional hazard models adjusted for variables that were significantly different among infection patterns. From April 2010 to September 2017, 71 of 1,027 subjects developed cervical dysplasia more severe than high-grade squamous intraepithelial lesion of the cervix. RESULTS: Of these 71 subjects, persistent infection, incidental infection, and clearance were noted in 30, 39, and 2 individuals, respectively. Based on changes in DNA results during follow-up, cumulative incidence was 27.2%, 10.4%, and 0.5% for persistent infection, incidental infection, and clearance, respectively. Compared to clearance, the adjusted hazard ratios for cervical dysplasia were 51.6 and 24.1 for persistent and incidental infections, respectively (p < 0.001). CONCLUSION: Individuals persistently infected with the same HPV types during the follow-up period had the highest risk of severe cervical dysplasia. Hence, it is necessary to monitor HPV types and infection patterns to prevent severe cervical precancerous lesions.
Atypical Squamous Cells of the Cervix ; Cervix Uteri ; Cohort Studies ; DNA ; Female ; Follow-Up Studies ; Human Papillomavirus DNA Tests ; Humans ; Incidence ; Korea ; Papillomavirus Infections ; Proportional Hazards Models ; Prospective Studies ; Republic of Korea ; Risk Factors ; Squamous Intraepithelial Lesions of the Cervix ; Uterine Cervical Dysplasia ; Uterine Cervical Neoplasms

BACKGROUND: Even though cervico-vaginal smears have been used as a primary screening test for cervical carcinoma, the diagnostic accuracy has been controversial. The present study aimed to evaluate the diagnostic accuracy of cytology for squamous intraepithelial lesion (SIL) and squamous cell carcinoma (SqCC) of the uterine cervix through a diagnostic test accuracy (DTA) review. METHODS: A DTA review was performed using 38 eligible studies that showed concordance between cytology and histology. In the DTA review, sensitivity, specificity, diagnostic odds ratio (OR), and the area under the curve (AUC) on the summary receiver operating characteristic (SROC) curve were calculated. RESULTS: In the comparison between abnormal cytology and histology, the pooled sensitivity and specificity were 93.9% (95% confidence interval [CI], 93.7%–94.1%) and 77.6% (95% CI, 77.4–77.8%), respectively. The diagnostic OR and AUC on the SROC curve were 8.90 (95% CI, 5.57–14.23) and 0.8148, respectively. High-grade squamous intraepithelial lesion (HSIL) cytology had a higher sensitivity (97.6%; 95% CI, 94.7%–97.8%) for predicting HSIL or worse histology. In the comparison between SqCC identified on cytology and on histological analysis, the pooled sensitivity and specificity, diagnostic OR, and AUC were 92.7% (95% CI, 87.3%–96.3%), 87.5% (95% CI, 87.2%–87.8%), 865.81 (95% CI, 68.61–10,925.12), and 0.9855, respectively. Geographic locations with well-organized screening programs had higher sensitivity than areas with insufficient screening programs. CONCLUSION: These results indicate that cytology had a higher sensitivity and specificity for detecting SIL and SqCC of the uterine cervix during primary screening.
Area Under Curve ; Carcinoma, Squamous Cell* ; Cervix Uteri* ; Diagnostic Tests, Routine* ; Epithelial Cells* ; Female ; Geographic Locations ; Mass Screening ; Odds Ratio ; ROC Curve ; Sensitivity and Specificity ; Squamous Intraepithelial Lesions of the Cervix*

OBJECTIVE: To evaluate the efficacy of modified Swede Colposcopic Index (MSCI) to predict high-grade lesion and cancer of cervix (CIN2+, cervical intraepithelial neoplasia grade 2 or worse) in women with abnormal cervical cytology who underwent a colposcopy. METHODS: We conducted a retrospective study and MSCI using 5 features of cervical lesions evidenced from colposcopy: acetouptake, margin and surface, vessels, lesion size, and location of lesion. Each feature was scored from cervicograhpic findings which transformation zone was completely seen. Odds ratio of each feature was obtained by logistic regression analysis. Receiver operating characteristic curve was used to assess the efficacy of summation score to predict CIN2+. An appropriate cut-off point score was assigned. RESULTS: Two hundred and twenty women were included in the study. The assigned score for each factor in level 1 to 3 was 1, 2 and 3 points with a total score of 15 points. The most appropriate cut-off points score for MSCI to predict CIN2+ was 11 points. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy using MSCI were 82.2%, 96.2%, 96.0%, 85.0%, and 90.0% respectively. CONCLUSION: MSCI showed a high efficacy for predicting CIN2+ in satisfactory colposcopy.
Cervical Intraepithelial Neoplasia ; Colposcopy ; Female ; Humans ; Logistic Models ; Odds Ratio ; Retrospective Studies ; ROC Curve ; Sensitivity and Specificity ; Squamous Intraepithelial Lesions of the Cervix ; Uterine Cervical Neoplasms

BACKGROUND: Hyperchromatic crowed groups (HCGs) are defined as three-dimensional aggregates of crowded cells with hyperchromatic nuclei, and are frequently encountered in cervicovaginal liquid-based cytology (LBC). Here, we aimed to examine the prevalence of HCGs in cervicovaginal LBC and the cytomorphological characteristics of various epithelial cell clusters presenting as HCGs.METHODS: We first examined the prevalence of HCGs in a “routine cohort” of LBC cytology (n=331), consisting of all cervicovaginal LBCs accessioned over 3 days from outpatient clinics (n=179) and the screening population (n=152). Then we examined a second “high-grade epithelial cell abnormalities (H-ECA) cohort” (n=69) of LBCs diagnosed as high-grade squamous intraepithelial lesion (HSIL), squamous cell carcinoma (SCC), or adenocarcinoma during 1 year.RESULTS: HCGs was observed in 34.4% of the routine cohort and were significantly more frequent in the epithelial cell abnormality category compared to the non-neoplastic category (p=.003). The majority of HCGs represented atrophy (70%). Of the 69 histologically confirmed H-ECA cases, all contained HCGs. The majority of cases were HSIL (62%), followed by SCC (16%). Individually scattered neoplastic cells outside the HCGs were significantly more frequent in SCCs compared to glandular neoplasia (p=.002). Despite the obscuring thick nature of the HCGs, examining the edges and the different focal planes of the HCGs and the background were helpful in defining the nature of the HCGs.CONCLUSIONS: HCGs were frequently observed in cervicovaginal LBC and were mostly non-neoplastic; however, neoplastic HCGs were mostly high-grade lesions. Being aware of the cytomorphological features of different HCGs is important in order to avoid potential false-negative cytology interpretation.
Adenocarcinoma ; Ambulatory Care Facilities ; Atrophy ; Carcinoma, Squamous Cell ; Cohort Studies ; Crows ; Epithelial Cells ; Mass Screening ; Prevalence ; Squamous Intraepithelial Lesions of the Cervix ; Uterine Cervical Neoplasms

OBJECTIVE: Human papillomavirus (HPV) testing is widely incorporated into cervical cancer screening strategies. Current screening requires pelvic examination for cervical sampling, which may compromise participation. The acceptance could be raised by introducing testing on vaginal swabs. We explored the interchangeability of vaginal swabs and cervical smears for HPV testing, by means of a prospective study conducted in female sex workers (FSWs). Besides, we report on the occurrence of 32 different HPV genotypes in FSW with low-grade squamous intraepithelial lesion (LSIL) or high-grade squamous intraepithelial lesion (HSIL). METHODS: Paired physician-collected vaginal swabs and cervical smears from 303 FSW were tested for HPV using the Abbott RealTime High-Risk HPV assay. Cervical cytology was examined on cervical smears. In case of HSIL/LSIL cytological classification (n=52), both samples were genotyped using INNO-LiPa HPV Genotyping Extra II. RESULTS: The overall prevalence of high-risk (HR)-HPV was 51%. In FSW with HSIL/LSIL cervical cytology, the sensitivity and specificity of vaginal samples for the detection of HR-HPV was 100% and 70% and for probable HR-HPV 100% and 91%. The mean number of genotypes identified in vaginal samples (mean=3.5; 95% confidence interval [CI]=2.8–4.2) was significantly higher than in cervical smear samples (mean=2.6; 95% CI=2.1–3.0) (p=0.001). The most frequently encountered HR-HPV genotypes were HPV16, 31, 51, and 52. CONCLUSION: As our study shows that vaginal swabs are equivalent to cervical smears for the detection of (probable) HR-HPV, vaginal swabs can be used for HPV testing in cervical cancer screening strategies. Given the acceptance of vaginal sampling, this finding offers an opportunity to boost screening coverage.
Chlamydia trachomatis ; Classification ; DNA ; Female ; Genotype ; Gynecological Examination ; Humans ; Mass Screening ; Mycoplasma genitalium ; Neisseria gonorrhoeae ; Papillomaviridae ; Prevalence ; Prospective Studies ; Sensitivity and Specificity ; Sex Workers ; Sexually Transmitted Diseases ; Squamous Intraepithelial Lesions of the Cervix ; Trichomonas vaginalis ; Uterine Cervical Neoplasms ; Vaginal Smears

OBJECTIVE: This study was to identify the risk factors for cytological progression in women with atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSIL). METHODS: We analyzed data from women infected with the human papillomavirus (HPV) who participated in the Korean HPV cohort study. The cohort recruited women aged 20–60 years with abnormal cervical cytology (ASC-US or LSIL) from April 2010. All women were followed-up at every 6-month intervals with cervical cytology and HPV DNA testing. RESULTS: Of the 1,158 women included, 654 (56.5%) and 504 (43.5%) women showed ASC-US and LSIL, respectively. At the time of enrollment, 143 women tested positive for HPV 16 (85 single and 58 multiple infections). Cervical cytology performed in the HPV 16-positive women showed progression in 27%, no change in 23%, and regression in 50% of the women at the six-month follow-up. The progression rate associated with HPV 16 infection was higher than that with infection caused by other HPV types (relative risk [RR], 1.75; 95% confidence interval [CI], 1.08–2.84; P=0.028). The cytological progression rate in women with persistent HPV 16 infection was higher than that in women with incidental or cleared infections (P < 0.001). Logistic regression analysis showed a significant relationship between cigarette smoking and cytological progression (RR, 4.15; 95% CI, 1.01–17.00). CONCLUSION: The cytological progression rate in HPV 16-positive women with ASC-US or LSIL is higher than that in women infected with other HPV types. Additionally, cigarette smoking may play a role in cytological progression.
Atypical Squamous Cells of the Cervix* ; Cohort Studies* ; Epidemiology ; Female ; Follow-Up Studies ; Human papillomavirus 16* ; Human Papillomavirus DNA Tests ; Humans ; Logistic Models ; Papillomaviridae ; Risk Factors* ; Smoking ; Squamous Intraepithelial Lesions of the Cervix