Peripheral blood immune cell parameters in patients with high-grade squamous intraepithelial lesion (HSIL) and cervical cancer and their clinical value: a retrospective study.

Objective: The objective of this study was to delineate the profile of peripheral blood lymphocytic indices in patients afflicted with high-grade squamous intraepithelial lesions (HSIL) and cervical neoplasms, and to elucidate the correlation of these hematologic markers with the clinicopathological spectra in individuals diagnosed with cervical carcinoma. Methods: We adopted a retrospective case-control modality for this investigation. An aggregate of 39 HSIL patients and 42 cervical carcinoma patients, who were treated in our facility from July 2020 to September 2023, were meticulously selected. Each case of cervical malignancy was confirmed through rigorous histopathological scrutiny. Concomitantly, 31 healthy female individuals, who underwent prophylactic health evaluations during the corresponding timeframe, were enlisted as the baseline control group. We systematically gathered and analyzed clinical demographics, as well as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), from peripheral blood samples. Pearson's correlation coefficient was deployed to dissect the interrelation between peripheral NLR and PLR concentrations and the clinicopathological features in the cervical cancer group. Results: Inter-group comparative analysis unveiled statistically substantial variances in the PLR and NLR values among the tripartite clusters (F = 36.941, 14.998, P < 0.001, respectively). Although discrepancy in NLR (P = 0.061) and PLR (P = 0.759) measures between the groups of cervical carcinoma and HSIL was not statistically appreciable, these indices were markedly elevated in the cervical carcinoma faction as juxtaposed with the normative control group (t = 5.094, 5.927; P < 0.001 for both parameters). A discernible gradation in peripheral blood PLR and NLR concentrations was noted when stratified by clinical stage and the profundity of myometrial invasion in cervical cancer subjects (P < 0.001). The correlation matrix demonstrated a positive liaison between peripheral blood PLR and the clinical gradation, as well as the invasiveness of the neoplastic cells into the muscularis propria (P < 0.05); a similar trend was observed with the NLR values (P < 0.05). Conclusion: Augmented NLR and PLR levels in peripheral blood specimens are indicative of HSIL and cervical malignancy. These hematological parameters exhibit a pronounced interconnection with clinical staging and muscular wall penetration depth, serving as potential discriminative biomarkers for the diagnosis and prognosis of cervical cancer.

Development of a machine learning-based model for predicting positive margins in high-grade squamous intraepithelial lesion (HSIL) treatment by Cold Knife Conization(CKC): a single-center retrospective study.

OBJECTIVES: This study aims to analyze factors associated with positive surgical margins following cold knife conization (CKC) in patients with cervical high-grade squamous intraepithelial lesion (HSIL) and to develop a machine-learning-based risk prediction model. METHOD: We conducted a retrospective analysis of 3,343 patients who underwent CKC for HSIL at our institution. Logistic regression was employed to examine the relationship between demographic and pathological characteristics and the occurrence of positive surgical margins. Various machine learning methods were then applied to construct and evaluate the performance of the risk prediction model. RESULTS: The overall rate of positive surgical margins was 12.9%. Independent risk factors identified included glandular involvement (OR = 1.716, 95% CI: 1.345-2.189), transformation zone III (OR = 2.838, 95% CI: 2.258-3.568), HPV16/18 infection (OR = 2.863, 95% CI: 2.247-3.648), multiple HR-HPV infections (OR = 1.930, 95% CI: 1.537-2.425), TCT ≥ ASC-H (OR = 3.251, 95% CI: 2.584-4.091), and lesions covering ≥ 3 quadrants (OR = 3.264, 95% CI: 2.593-4.110). Logistic regression demonstrated the best prediction performance, with an accuracy of 74.7%, sensitivity of 76.7%, specificity of 74.4%, and AUC of 0.826. CONCLUSION: Independent risk factors for positive margins after CKC include HPV16/18 infection, multiple HR-HPV infections, glandular involvement, extensive lesion coverage, high TCT grades, and involvement of transformation zone III. The logistic regression model provides a robust and clinically valuable tool for predicting the risk of positive margins, guiding clinical decisions and patient management post-CKC.

Analysis of the clinical characteristics and surgical methods of high-grade squamous intraepithelial lesions of the cervix in postmenopausal women: A retrospective case study.

The purpose of this study was to thoroughly evaluate the clinical features and surgical options for high-grade squamous intraepithelial lesions (HSIL) in postmenopausal women. A total of 308 patients diagnosed with HSIL through colposcopic cervical biopsy and endocervical curettage were included. Their clinical characteristics, surgical treatments, and postoperative pathology were analyzed. Key findings include: 1. Patients with positive preoperative thinprep cytologic test (TCT) results and postoperative pathology indicating HSIL or squamous cell carcinoma (≥HSIL) were significantly more frequent than those with negative preoperative TCT results (P < .05). 2. Univariate analysis indicated significant impacts of TCT, human papillomavirus (HPV) type, transformation zone (TZ) location, and surgical technique on postoperative pathology (P < .05). 3. Logistic regression analysis confirmed significant influences of TCT, HPV type, TZ location, and surgical method on postoperative pathology outcomes (P < .05), showing that each unit increase in TZ raised the probability of ≥HSIL in postoperative pathology by 49.7%. In surgical comparisons, cold knife conization (CKC) and extrafascial hysterectomy resulted in 8.379 and 4.427 times higher probabilities of ≥HSIL in postoperative pathology, respectively, compared to loop electrosurgical excision procedure (LEEP). 4. Surgical methods significantly influenced margin results (P < .05). After LEEP, 17.5% of cases had positive margins, compared to 9.4% after CKC, and 3.7% after extrafascial hysterectomy, indicating the highest rate of positive surgical margins occurred with LEEP. 1. Combined TCT and HPV screening is crucial for cervical cancer prevention, early detection, and management in postmenopausal women. Women with positive results for both TCT and HPV should undergo colposcopic cervical biopsy and endocervical curettage. 2. For patients with TZ3, CKC is the recommended surgical option. 3. CKC is the preferred treatment for postmenopausal women with HSIL, as it effectively diagnoses and treats the lesion, showing superior outcomes in managing postmenopausal HSIL.

Clinical analysis of 314 patients with high-grade squamous intraepithelial lesion who underwent total hysterectomy directly: a multi-center, retrospective cohort study.

OBJECTIVE: To identify the risk factors of cervical high-grade squamous intraepithelial lesion(HSIL) complicated with occult cervical cancer and standardize the management of initial treatment for HSIL. METHOD: The clinical data of patients who underwent total hysterectomy directly due to HSIL in the obstetrics and gynecology department of two tertiary hospitals and three secondary hospitals from 2018 to 2023 were collected. Their general characteristics, pathological parameters and survival status were analyzed. Logistic regression model was used to analyze the correlation between clinical parameters and postoperative pathological upgrading. RESULT: 1. Among the 314 patients with HSIL who underwent total hysterectomy directly, 73.2% were from primary hospitals. 2. 25 patients (7.9%) were pathologically upgraded to cervical cancer, all of which were early invasive cancer. 3. Up to now, there was no recurrence or death in the 25 patients with early-stage invasive cancer, and the median follow-up period was 21 months(range 2-59 months). 4. Glandular involvement(OR 3.968; 95%CI 1.244-12.662) and lesion range ≥ 3 quadrants (OR 6.527; 95% CI 1.78-23.931), HPV 16/18 infection (OR 5.382; 95%CI 1.947-14.872), TCT ≥ ASC-H (OR 4.719; 95%CI 1.892-11.766) were independent risk factors that affected the upgrading of postoperative pathology. 5. The area under the curve (AUC) calculated by the Logistic regression model was 0.840, indicating that the predictive value was good. CONCLUSION: There is a risk of occult cervical cancer in patients with HSIL. Glandular involvement, Lesion range ≥ 3 quadrants, HPV 16/18 infection and TCT ≥ ASC-H are independent risk factors for HSIL combined with occult cervical cancer. The prognosis of biopsy-proved HSIL patients who underwent extrafascial hysterectomy and unexpected early invasive cancer was later identified on specimen may be good.

Cervical precancerous and cancerous lesions screening using Pap smear test at Provincial Referral Hospital of Bukavu, Eastern DR Congo: profile and recommendations to stakeholders.

Introduction: cervical cancer is a health concern worldwide. The South Kivu Province in the Eastern DR Congo is facing many cases of this disease but poorly screened and reported. The objective of this was to determine the prevalence of cell abnormalities at cervical cytology in a tertiary teaching hospital in Bukavu and their association with common risk factors of cervical cancer. Methods: a cross-sectional study was conducted on 142 women attending the Provincial Referral Hospital of Bukavu (HPGRB) from February to December 2021. Quantitative variables were described by their median following their asymmetric distributions and the qualitative variables in absolute and relative frequencies. Then the Chi-square test was used for the comparison of proportion. Results: forty-five percent of the participants had between three and five children. Twenty-two (15.5%) of the 142 patients reported to have two or more sexual partners and 17.5% reported the use of hormonal contraception. The prevalence of cell abnormalities at cervical cytology was 17% of which Low- Grade Squamous Intraepithelial Lesion (LSIL) was the most representative (12.9%). There was no statistically significant association between the common cervical risk factors and the occurrence of cell abnormalities. Conclusion: cervical pre-cancerous lesions are frequent in South Kivu province. The Pap smear test remains an early and affordable screening method and constitutes a secondary prevention strategy in women of 18 years and older in a low-income country such as DR Congo where vaccination against HPV is still hypothetic.

Chromocolposcopy with fluorescein sodium for detection of premalignant and malignant lesions of the cervix: A cross-sectional study.

OBJECTIVE: The aim of the study was to explore the utility of fluorescein sodium (FNa) as a contrast agent for colposcopy to detect premalignant and malignant lesions of cervix. The primary objective was to determine and compare the percentage detection of premalignant and malignant lesions of FNa and acetic acid (AA) positive areas. METHODS: This study included 120 screen positive women who underwent colposcopy using both 3% AA and FNa (0.06%). Observations for FNa staining were made under blue filter and directed biopsies were taken from acetowhite and fluorescent green areas. Benign lesions were considered as disease-negative and low grade squamous intraepithelial lesions (LSIL), high grade SIL (HSIL), and invasive cancer were considered as disease-positive. Correlation between histopathology and FNa and AA was determined by Kappa statistics. RESULTS: The mean age was 39.59 ± 10.73 years and median parity was 2. Out of 120 patients, 57 had benign lesions, 18 had LSIL, 33 had HSIL and 12 had invasive carcinomas. Sensitivity was 98.41% versus 64.91% respectively and specificity was 85.71% versus 35.09% respectively with FNa and AA. Diagnostic accuracy of FNa and AA was 82.50% versus 61.60%. There was good agreement between FNa staining and final histopathology and fair agreement between AA application and HPE (κ = 0.643 vs 0.213, P < 0.001). CONCLUSION: Using FNa as a contrast agent during colposcopy results in greater accuracy for detection of premalignant and malignant lesions of the cervix as compared to AA.

Challenging lesions in cervical cytology: The elusive HSIL.

Cervical cytology has been an integral part of cervical cancer screening since the mid-20th century with the implementation of screening protocols utilising Pap testing. During that time, cervical cancer has gone from the leading cause of cancer deaths in women to not even appearing in the top 10 causes of US cancer deaths. However, despite its long and widespread use, cervical cytology remains a diagnostically challenging area in the practice of cytopathology. Of particular importance for diagnosticians is the accurate diagnosis of high-grade squamous intraepithelial lesions (HSILs), given the significant risk of progression to invasive cervical cancer and the importance to patient management. Therefore, this review is presented in order to highlight the diagnostic features of HSIL, its various appearances, and important benign and neoplastic differential considerations with an emphasis on morphological clues that can aid in distinguishing between these different processes.

Histopathologic Follow-Up of Women with Inadequate ThinPrep™ Cervical Pap Tests and Positive High-Risk Human Papillomavirus Test Results.

INTRODUCTION: We found only a few studies that had performed high-risk human papillomavirus (hrHPV) analyses of inadequate ThinPrep™ Papanicolaou (Pap) tests. Therefore, this study aimed to analyze unsatisfactory ThinPrep Pap tests using hrHPV tests. The colposcopic biopsy results of cases with an unsatisfactory ThinPrep Pap test and positive hrHPV results were revealed. METHODS: Between January 1, 2018, and October 31, 2022, 965 (3.7%) of 25,958 liquid-based cytology specimens were evaluated as unsatisfactory. Ninety-five (9.8%) of 965 patients were positive for hrHPV. The colposcopic evaluation was performed in 28 (29.4%) of 95 patients, in whom 23 tests were adequate. RESULTS: Twenty-three colposcopy biopsy results showed that 17 (73.9%) of 23 patients had benign biopsy results. High-grade squamous intraepithelial lesions were observed in three (13%) of the 23 patients, and low-grade squamous intraepithelial lesions were observed in two (8.6%) of the 23 patients. One of the 23 (4.3%) patients had keratinized squamous cell carcinoma of the cervix diagnosed histologically, although no tumor was visible upon gynecologic examination. CONCLUSION: For the management of unsatisfactory Pap tests, The American Society for Colposcopy and Cervical Pathology (ASCCP) recommends repeat cytology within 2-4 months. Evaluation of such patients using hrHPV tests may triage those with squamous intraepithelial lesions, even invasive cervical cancer. More studies with a larger number of cases are needed to analyze the hrHPV status and biopsy follow-up of cases with unsatisfactory cytology.

[Analysis of natural regression and influencing factors of HSIL in the cervix of childbearing age patients].

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.

Recurrent High-Grade Squamous Intraepithelial Lesion After Loop Excision Procedure Versus Loop Procedure With Top Hat.

OBJECTIVE: To evaluate single-pass loop electrosurgical excision procedure (LEEP-SP) versus LEEP with top hat (LEEP-TH) in terms of treatment failure defined as high-grade squamous intraepithelial lesion (HSIL) cytology within 2 years' follow-up. METHODS: This single-institution cohort study used a prospectively collected cervical dysplasia database including all patients who underwent LEEP-SP or LEEP-TH for biopsy-proven cervical intraepithelial neoplasia between 2005 and 2019. RESULTS: Of 340 patients included, 178 underwent LEEP-SP and 162 LEEP-TH. The LEEP-TH patients were more likely to be older (mean age, 40.4 vs 36.5 years; p < .001) and have a positive preprocedure endocervical sampling (68.5% vs 11.8%; p < .001). Positive margins were found in 23 LEEP-SP (12.9%) and in 25 LEEP-TH (15.4%; p = .507). There was no significant difference in depth of excision between LEEP-SP (13.21 ± 23.19 mm) and LEEP-TH (17.37 ± 28.26 mm; p = .138). At 2 years, there was no difference in the rates of HSIL cytology (5.2% vs 6.3%; p = .698), any positive human papillomavirus test, or HSIL cytology (25% vs 15%; p = .284). The 57 patients undergoing repeat excision were more likely to be older (mean age, 40.95 vs 37.52 years; p = .023), have had a LEEP-TH (26.3% vs 73.7%; p < .001), and have initial cytologic HSIL (64.9% vs 35.0%; p < .001). CONCLUSIONS: In this single-institution study, there is no difference in the rate of recurrent HSIL in patients undergoing LEEP-SP versus LEEP-TH. A LEEP-TH may have limited additional benefit over a LEEP-SP in the treatment of cervical HSIL.

Association of P16, Ki-67, and CD44 expression in high-grade squamous intraepithelial neoplasia and squamous cell carcinoma of the cervix.

Background: Stem cells exist in niches in the cervical tissue at squamocolumnar junction, which when infected with HR-Human Papilloma Virus undergo malignant transformation to cancer stem cells and have a role in carcinogenesis and metastasis. The expression of CD44, P16, and Ki67 in high-grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma (SCC) is assessed in this study. Materials and Methods: Twenty-six cases each of normal cervix, HSIL, and SCC of cervix cases were subjected to immunohistochemistry markers; p16, Ki-67, and CD44. The association of expression of these markers between normal, HSIL, SCC cervix, and clinic-pathological parameters was statistically analyzed. P < 0.05 was considered significant. Results: Of 26 cases of HSIL, 61.5%, 7.7%, and 30.8% cases were positive, ambiguous, and negative respectively for p16 expression. About 11.5%, 53.8%, and 34.6% of cases were strongly positive, positive, and weakly positive, respectively, for Ki-67 expression. About 42.3%, 42.3%, and 15.4% cases were strongly positive, positive, and weakly positive, respectively, for CD44 expression. Among 26 cases of SCC of the cervix 92.3% and 7.7% were positive and ambiguous respectively. About 73.1% and 26.9% of cases were strongly positive and positive, respectively, for Ki-67 expression. 65.4%, 30.8%, and 3.8% of cases were strongly positive, positive, and weakly positive, respectively, for CD44 expression. p16, Ki-67, and CD44 expression between the three groups were statistically significant. p16 expression versus FIGO stage including lymph node involvement and CD44 expression versus lymph node involvement in carcinoma cervix was statistically significant. Conclusion: Expression of p16, Ki-67, and CD44 increases as the lesion progress from normal to HSIL to carcinoma cervix. p16 and CD44 expression increase with lymph node involvement. P16 expression was maximum in Stage II than Stage III.

Early effect of bivalent human papillomavirus vaccination on cytology outcomes in cervical samples among young women in the Netherlands.

BACKGROUND: The first HPV-vaccine eligible cohorts in the Netherlands will enter the cervical screening program in 2023. However, a substantial number of young women already have had a cervical sample taken before entry into the regular screening program. This study was initiated to explore early effects of HPV vaccination on detection of cytological abnormalities in cervical samples of women younger than the screening age. METHODS: Results of cervical samples were obtained from the Dutch National Pathology Databank (PALGA) and were linked to the women's HPV vaccination status from the national vaccination registry (Praeventis) (N = 42,171). Occurrence of low-grade and high-grade squamous intraepithelial lesions or worse (LSIL and HSIL+) and high-risk HPV positive tests (hrHPV) in the first cervical sample were compared between vaccinated and unvaccinated women by multivariable logistic regression analysis, corrected for age at cervical sampling and age of vaccination (12/13 years, ≥ = 14 years). RESULTS: For fully vaccinated women (three- or two-dose schedule), statistically significant reductions were seen for all outcomes compared to unvaccinated women (hrHPV: adjusted OR, 0.70, 95% CI, 0.63-0.79; LSIL: 0.70, 0.61-0.80; HSIL+: 0.39, 0.30-0.51). CONCLUSIONS: By linking nation-wide registries on pathology and vaccination, we show significant beneficial early effects of HPV-vaccination on LSIL, HSIL+, CIN3/AIS/carcinoma and hrHPV detection in young women upto 24 years of age who have a cervical sample taken before entry into the cervical cancer screening program.

Higher clearance rates of multiple HPV infections may explain their lower risk of HSIL: A retrospective study in Wenzhou, China.

Persistent human papilloma virus (HPV) infection is known to be associated with cervical lesions. The chief object of the study is to investigate if the pathogenicity of multiple HPV infections is different from a single infection. Furthermore, we would like to corroborate the discrepancy with clearance rates. Between August 1, 2020, and September 31, 2021, 5089 women underwent a colposcopy-directed biopsy in our hospital. We divided the 2999 patients who met the criteria into multiple and single HPV infection groups. The HPV genotypes were identified using the flow cytometry fluorescence hybridization technology. Binary logistic regression and survival analysis were used to perform statistics. Among HPV-positive individuals, 34.78% (1043/2999) were positive for 2 or more HPV types. After adjusting for the main factors, compared with single infection, multiple infections were associated with a significantly decreased risk of high squamous intraepithelial lesions (HSIL) (odds ratio [OR]: 0.570; 95% confidence interval [CI]: 0.468-0.694). In the mean time, the clearance rates of multiple infections were significantly higher (OR: 2.240; 95% CI: 1.919-2.614). When analyzing specific types covered by the 9-valent HPV vaccine, consistency between the lower risk of HSIL and the higher clearance rate was found in the most groups. Compared with a single infection, multiple HPV infections have a lower risk of HSIL, which may be related to its higher clearance rate. It suggests that aggressive treatment of multiple HPV infections early in their detection may be beneficial.

Recurrence in Cervical High-Grade Squamous Intraepithelial Lesion: The Role of the Excised Endocervical Canal Length-Analysis of 2,427 Patients.

OBJECTIVE: This study aimed to evaluate the influence of the excised canal length on relapse rates of cervical high-grade squamous intraepithelial lesion (HSIL) treated by loop electrosurgical excision procedure and to find a cut-off point, above which lower recurrence rates could be observed, with low probability of compromising future obstetric outcome, and the relationship with other individual factors related to HSIL recurrence. METHOD: This was a retrospective cohort study of 2,427 women diagnosed with cervical intraepithelial neoplasia CIN2+ who underwent cervical conization using the high-frequency loop electrosurgical excision procedure surgery technique, to analyze the role of endocervical canal length associated with individual factors in the recurrent disease after CIN2+ treatment and determine a cut-off point for the excised canal length needed to decrease the risk of disease relapse. RESULTS: In 2,427 cases, the relapse rate of HSIL treated was 12%. Compromised margins of conization, HIV+, and endocervical canal length were related directly to relapses ( p < .001). The cut-off point, by receiver operating characteristic curve, to calculate the endocervical canal length related to relapses was 1.25 cm of canal excised. Canal length of less than 1.25 cm increased the recurrence rate 2.5 times. Compromised margins and HIV+ increased recurrence rates by more than 5 times. CONCLUSION: Cervical HSIL recurrence was directly related to the endocervical canal length: excised canal length of 1.25 cm or more decreases recurrence rate; HIV and compromised margins increase the chance of recurrence by more than 5 times.

Analysis of natural regression and influencing factors of HSIL in the cervix of childbearing age patients / 中华妇产科杂志

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.

Efficacy of photodynamic therapy with 5-aminolevulinic acid for the treatment of cervical high-grade squamous intraepithelial lesions with high-risk HPV infection: A retrospective study.

BACKGROUND: The current principle of clinical management of cervical high-grade squamous intraepithelial lesion(HSIL) is surgical excision. However excisional procedures of the uterine cervix may have a negative impact on fertility. Topical photodynamic therapy(PDT) is a non-invasive and selective tissue destruction. We investigated the clinical efficacy of PDT for cervical HSIL with high-risk human papilloma virus(HPV) infection. METHODS: A retrospective study consisting of 96 patients aged 20-50 years with a histologically confirmed cervical HSIL with high-risk HPV infection from July 2018 to June 2022 was carried out. Patients were treated with six times of 20% 5-aminolevulinic acid photodynamic therapy (5-ALA PDT) at intervals of 7-14 days. Three months after treatment, the effect was evaluated through HPV typing and colposcopy directed biopsy. Six and twelve months after treatment, TCT and HPV tests were carried out. RESULTS: Three months after 5-ALA PDT treatment, among 96 HSIL with high-risk HPV infection patients, the total lesion regression rate was 89.58%(86/96), and the HPV clearance rate was 79.17 % (76/96) at 3 months follow-up. At 6 and 12 months follow-up, the patients who was HSIL pathological regression and negative HPV at 3 months follow-up continued negative results in both TCT and HPV. All patients with ineffective 5-ALA PDT treatment had persistent HPV infections. There was no significant difference in the HSIL regression rate and HPV clearance rate among different age groups. The main side effects of PDT were abdominal pain and increased vaginal secretions. Univariate analysis showed that the different severity of cervical cytology was associated with lesion regression rate in 5-ALA PDT treatment. The HSIL regression rate of TCT

Effects of Menstrual Cycle on Various Morphologies of High-Grade Squamous Intraepithelial Lesions in SurePath™ Liquid-Based Cervical Cytology.

INTRODUCTION: The morphology of high-grade squamous intraepithelial lesion (HSIL) on Papanicolaou (Pap) smears widely varied, including syncytial aggregates, sheets, and scattered single cells, and no particular cellular pattern is consistently observed. Therefore, this study aimed to determine whether the menstrual cycle affects the cellular pattern of HSILs, an effort to avoid false negatives due to the oversight of scattered small single HSIL cells in the cytological triage of human papillomavirus-positive women. METHODS: A total of 147 HSIL samples of liquid-based cytology (LBC) in patients with cervical intraepithelial neoplasia grade 2 or 3 were obtained, and then, the relationship between cellular patterns, such as single-cell-like and syncytial aggregates, and menstrual cycles classified into six phases was analyzed. If a syncytial aggregate was present, the number of cells constituting the aggregate was visually counted under the microscope. RESULTS: HSILs in scattered single cells and small sheets of <6 on LBC samples accounted for 43% (23/54) during the late proliferative phase of the menstrual cycle. A moderately strong statistically significant association was observed between cellular patterns and menstrual cycles (χ2 [3] = 9.423, p < 0.05) (Cramer's V = 0.253). The value of adjusted residuals showed a statistically significant increased proportion of single-cell-like patterns during the late proliferative phase (p < 0.01). CONCLUSIONS: The present study demonstrated that HSIL cells in Pap smears in the late proliferation phase have a high frequency of single-cell-like patterns. In human papillomavirus-positive Pap smears with a clean background and predominantly superficial cells, careful microscopic observation by targeting single HSIL cells can potentially reduce false negatives.

Cervical Precancers Originate From Infected Proliferating Reserve Cells: A Comparative Histologic and Genetic Study of Thin and Thick High-grade Squamous Intraepithelial Lesions.

Human papillomavirus (HPV)-induced invasive cervical squamous cell cancer (SCC) develop via high-grade squamous intraepithelial lesion (HSIL). In contrast to classic thick HSIL, thin HSIL (≤9 cell layers) are poorly documented. This study compares histology, HPV genotypes, and aberrations in 50 cancer genes of 45 thin HSIL to 45 thick HSIL, 20 pT1a SCC, and 40 ≥pT1b SCC. Thin HSIL arose from proliferating reserve cells within endocervical epithelium or immature metaplasia throughout the transformation zone after infection with high-risk HPV genotypes (36/45; 80%), and 20% non-high-risk HPV genotypes compared with 2.5% thick HSIL, pT1a SCC, and ≥pT1b SCC. Thin HSIL were multifocal proliferations with varying epithelial thickness between 1 and 2 to 9 cell layers, with occasional transitions to thick HSIL or concomitant lesions of thick HSIL. Overall, 40% thin HSIL were located distant to and most thick HSIL occurred near or at the squamocolumnar junction. Only 20% thick HSIL showed koilocytosis. All HSIL lacked somatic gene mutations, compared with 30% pT1a and 55%≥pT1b SCC. Overrepresented rare germline variants in the MET, JAK3, and FGFR3 genes occurred in all patient groups. In summary, thin and thick HSIL arose independently of somatic gene mutations. The maturation level of the squamous epithelium at the time of transforming infection determines if a thick HSIL develops directly from HPV-infected proliferating reserve cells via thin HSIL or in stratified glycogenated squamous epithelium via low-grade squamous intraepithelial lesion. These observations raise doubts about the biological relevance of separation into thin and thick HSIL. The oncogenic potential of HPV genotypes but also germline variants may influence the natural history.

Comparative measurement of D- and L-lactic acid isomers in vaginal secretions: association with high-grade cervical squamous intraepithelial lesions.

PURPOSE: Identification of low-cost protocols to identify women at elevated susceptibility to develop cervical intra-epithelial abnormalities would aid in more individualized monitoring. We evaluated whether quantitation of the D- and L-lactic acid isomers in vaginal secretions could differentiate women with normal cervical epithelia from those with a low (LSIL) or high (HSIL) grade squamous intraepithelial lesion or with cervical cancer. METHODS: Vaginal samples, collected from 78 women undetgoing cervical colposcopy and biopsy, were tested for pH, bacterial composition by Gram stain (Nugent score) and concentrations of D- and L-lactic acid by a colorimetric assay. RESULTS: Subsequent diagnosis was 23 women with normal cervical epithelium, 10 with LSIL, 43 with HSIL and 2 with cervical cancer. Vaginal pH and Nugent score were comparable in all subject groups. The concentration of L-lactic acid, but not D-lactic acid, as well as the L/D-lactic acid ratio, were significantly elevated (p < 0.01) in women with HSIL and cervical cancer. CONCLUSION: Comparative measurement of vaginal D- and L-lactic acid isomers may provide a low-cost alternative to identification of women with an elevated susceptibility to cervical abnormalities.