[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.

[Analysis of related factors for cervical intraepithelial neoplasia â ¡+ detection in grade 1 abnormal colposcopic finding of cervix].

Objective: To screen out high risk factors of cervical intraepithelial neoplasia (CIN) of grade Ⅱ or worse (CIN Ⅱ+) by analyzing related factors for CIN Ⅱ+ detection in grade 1 abnormal colposcopic finding (G1) of cervix and provide reference for individual management of colposcopic performance. Methods: A retrospective study was performed on patients who were reffered to colposcopy for abnormal results of cervical cancer screening and only had G1 colposcopic findings of cervix at the First Affiliated Hospital of Nanjing Medical University, from April 2017 to January 2021. The factors influencing the detection of CIN Ⅱ+ were analyzed by univariate and multivariate analysis. Results: (1) A total of 403 patients were included in this study whose median age was 38 years old (range: 22-67 years old), and utimately 108 had high-grade squamous intraepithelial lesion, 1 had adenocarcinoma in situ and 1 had adenocarcinoma. The overall detection rate of CIN Ⅱ+ was 27.3% (110/403). (2) Univariate analysis showed that the detection rate of CIN Ⅱ+, in patients ≥50 years old was higher than that in patients <50 years old (38.3% vs 25.4%; χ²=4.328, P=0.037), and in HPV 16 positive cases was higher than that in non-HPV 16 positive cases (41.8% vs 21.8%; χ²=16.080, P<0.01); as the cytological severity (χ²=6.775, P=0.009) and the number of involving quadrants (χ²=31.117, P<0.01) increased, the risk of CIN Ⅱ+ detection increased; but the types of colpolscopic signs were not related to detection of CIN Ⅱ+(χ²=0.323, P=0.851). Multivariable analysis showed that the age of ≥50 years old (OR=2.504, 95%CI: 1.299-4.830, P=0.006), HPV 16 positive type (OR=3.353, 95%CI: 2.004-5.608, P<0.01) and the increase of involving quadrants (OR=1.899, 95%CI: 1.518-2.376, P<0.01) were independent risk factors. (3) The detection rate of CIN Ⅱ+ was highest in the women with HPV 16 positive type and four quadrants of G1 (73.7%), while lowest in the women with non-HPV 16 positive type and one quadrant of G1 (10.4%). Conclusions: The age of ≥50 years old, HPV 16 positive type and the increase of involving quadrants are independent risk factors of detecting CIN Ⅱ+ in G1 colposcopic findings. So the key point of the individual management of G1 groups with different risk stratification is to adequately biopsy in high-risk group to avoid miss diagnosis of CIN Ⅱ+.

[Optimizing biopsy procedures during colposcopy and detection of high-grade cervical lesions].

Objective: To investigate the value of biopsies on diagnosing cervical intraepithelial neoplasia of grade 2 or worse (CIN Ⅱ+), and optimize biopsy procedures of risk-based colposcopy practice. Methods: A prospective study was performed on 346 women referred to colposcopy following abnormal cervical cancer screening results at the First Affiliated Hospital of Nanjing Medical University, from April 2017 to December 2019. Up to 4 cervical biopsies were taken during colposcopy and each biopsy specimen was evaluated separately in histology. CIN Ⅱ+ identified by any biopsy was the reference standard of disease used to evaluate the diagnostic value of targeted biopsy and random biopsy, and to quantify the improved detection of CIN Ⅱ+ by taking multiple biopsies. Cervical cytology, HPV genotyping, and colposcopic impression were used to establish different risk strata to select various multiple biopsies procedures during colposcopy to improve accuracy and efficiency of CIN Ⅱ+ detection. Results: In total 346 women, 190 (54.9%, 190/346) cases of them were diagnosed as CIN Ⅱ+. (1) In total 346 women, 96.8% (184/190) CIN Ⅱ+ were detected by targeted biopsies, 27.9% (53/190) CIN Ⅱ+ were detected in biopsies targeted grade 1 abnormal colposcopic findings (G1) on the cervix, and 68.9% (131/190) CIN Ⅱ+ were detected in biopsies targetrd grade 2 abnormal colposcopic findings (G2) on the cervix. Colposcopy had a sensitivity of 68.9% when the biopsy threshold was G2, sensitivity increased to 96.8% when the biopsy threshold was defined to be G1. Among women with G1, adding 2 targeted biopsies to the first biopsy were sufficient to detect all CIN Ⅱ+, among women with G2, adding 1 targeted biopsy was sufficient. (2) Among 270 women, random biopsies targeted normal colposcopic findings on the cervix were performed in addition to targeted biopsies and in total 3.2% (6/190) additional CIN Ⅱ+ were detected. As the number of cervical quadrants involved by abnormal colposcopic images increased, random biopsy detected fewer CIN Ⅱ+ that would have otherwise been missed by targeted biopsies (P=0.010). (3) Women with atypical squamous cells,cannot exclude high grade squamous intraepithelial lesion (ASC-H), high grade squamous intraepithelial lesion (HSIL) or atypical glandular cell (AGC) referral cytology, HPV 16-positive, G2 were more likely to have CIN Ⅱ+(P<0.01); for those meeting only one category, the yield of CIN Ⅱ+ increased from 34.0% for one biopsy to 51.0% for two biopsies, the absolute increase in CIN Ⅱ+ yield increased from the first to the second biopsy was 17.0%, two biopsies were sufficient to detect all CIN Ⅱ+; for those meeting at least two categories, the yield of CIN Ⅱ+ increased from 90.7% for one biopsy to 92.6% for two biopsies, the absolute increase in CIN Ⅱ+ yield increased from the first to the second biopsy was 1.9%, two biopsies were sufficient to detect all CIN Ⅱ+; for those not meeting any category, the yield of CIN Ⅱ+ increased from 8.8% for one biopsy to 17.6% for two biopsies, to 23.5% for three biopsies, the absolute increase in CIN Ⅱ+ yield increased from the first to the second biopsy, from the second to the third biopsy was 8.8%, 5.9%, three biopsies were sufficient to detect all CIN Ⅱ+. Conclusions: Performing multiple targeted biopsies could improve efficiency of CIN Ⅱ+ detection. Adding random biopsies to multiple targeted biopsies showed very limited additional benefit for detection of CIN Ⅱ+. The biopsy procedures undertaken during the colposcopy visit could be modified based on various colposcopic impressions and reasons for referral.

[Discussion on the diagnosis and treatment of high-grade squamous intraepithelial lesions in post-menopausal women].

Objective: To analyze the performance of colposcopy and investigate the diagnosis and treatment characteristics of high-grade squamous intraepithelial lesion (HSIL) diagnosed by cervical tissue sampling in post-menopausal women. Methods: A retrospective study was performed on 1 449 patients with HSIL diagnosed by cervical tissue sampling under colposcopy and treated by loop electrosurgical excision procedure (LEEP) or extrafascial hysterectomy as the primary therapy at the First Affiliated Hospital of Nanjing Medical University, from November 2015 to October 2017. In order to investigate the diagnosis and treatment of HSIL in post-menopausal women, a case-control study was conducted to compare the difference in performance of colposcopy and treatment modality between 213 post-menopausal patients (14.7%, 213/1 449) and 1 236 pre-menopausal patients (85.3%, 1 236/1 449). Results: (1)The proportion of cases pathologically upgraded to cervical cancer was significantly greater in post-menopausal patients (9.4%, 20/213) compared with pre-menopausal patients (3.8%, 47/1 236; P<0.05). (2) The proportion of ≥HSIL diagnosed by colposcopy showed no significant difference between post-menopausal patients (76.1%, 162/213) and pre-menopausal patients (78.2%, 967/1 236; P=0.479). The proportion of type Ⅲ transformation zone (TZ) was significantly greater in post-menopausal patients (91.1%, 194/213) compared with pre-menopausal patients (59.1%, 731/1 236; P<0.05). The rate of missed diagnosis of cervical cancer was significantly higher in type Ⅲ TZ (6.4%, 59/925) compared with type Ⅰ and(or) Ⅱ TZ (1.5%, 8/524; P<0.05). The proportion of HSIL detected by endocervical curettage alone was greater in post-menopausal patients (9.9%, 21/213) compared with pre-menopausal patients (2.6%, 32/1 236; P<0.05). (3)Initial treatment with LEEP: the positive rate of endocervical margin was significantly greater in post-menopausal patients (20.5%, 36/176) compared with pre-menopausal patients (10.5%, 130/1 236;P<0.05); in patients who were diagnosed as HSIL after LEEP, the positive rate of endocervical margin and the residual rate were both greater in post-menopausal patients compared with pre-menopausal patients [15.4% (25/162) versus 8.8% (105/1 189), P=0.008; 52.0% (13/25) versus 26.7% (28/105), P=0.014]. (4)Thirty-seven post-menopausal patients were treated by extrafascial hysterectomy as the primary therapy, 5 cases (13.5%, 5/37) were diagnosed as cervical cancer (stage Ⅰa1) after the surgery. Conclusions: (1) The lesions of HSIL in post-menopausal patients still have definite features under colposcopy as same as pre-menopausal patients. Endocervical curettage could help detect more HSIL in post-menopausal patients. Compared with pre-menopausal patients, post-menopausal HSIL patients have an increased risk of cervical cancer and are more likely missed by cervical tissue sampling. (2) LEEP has the dual effects of diagnosis and treatment, and is still the recommended treatment for post-menopausal HSIL patients. However, the increase in positive rate of endocervical margin and residual rate requires further active intervention. (3) Considering those post-menopausal HSIL patients who cannot accept conization as the initial treatment, the selection of hysterectomy type requires more thorough study.

[Analysis of the missed diagnosis of invasive carcinoma under the microscope in HSIL diagnosed by colposcopy-guided biopsy and related influencing factors].

Objective: To observe the missed diagnosis of invasive carcinoma under the microscope (ICUM) in high grade squamous intraepithelial neoplasia (HSIL) , and analyze associated factors influencing missed ICUM. Methods: A retrospective study was performed on patients diagnosed with HSIL by colposcopy-guided biopsy and treated with loop electrosurgical excision procedure (LEEP) at the First Affiliated Hospital of Nanjing Medical University, from December 2014 to December 2016. They were non-pregnant, ≤50 years old and the cervical volume without obvious enlargement and exogenous surface without and ulcerative lesions. A total of 283 cases with early cervical cytology results, never received cervical traumatic treatment or cervical biopsy in another hospital before, and their colposcopic images were clear enough to reevaluate. The ultimate pathological diagnosis was based on the higher-level pathological diagnosis between the results of cervical biopsy and LEEP to evaluate ICUM missed in HSIL and the risk factors. Results: (1) Among the 283 cases with HSIL diagnosed by colposcopy-directed biopsy, 44 cases (15.5%, 44/283) were missed diagnosis of ICUM, which consisted of 29 cases Ⅰ a1, 4 cases Ⅰ a2 and 11 cases Ⅰ b1 in the ultimate pathology. (2) Analysis of associated factors for missed ICUM: univariate analysis showed that, as the age increased, the risk of missed ICUM also increased (the rates of missed diagnosis for <30, 30-39, 40-50 years were 7.7%, 11.5%, 22.0%, respectively; χ(2)=6.254, P=0.012 by trend test) . The more the number of high-grade features, the higher risks (the rates of missed diagnosis for 1, 2, 3, 4 high-grade features were 10.2%, 17.6%, 23.8%, 30.8%, respectively; χ(2)=7.686, P=0.006 by trend test) . The locations of HSIL were only endocervical, only ectocervical and mixed, the risk increased by this sequence (2.8%, 5.1%, 28.7%; χ(2)=26.193, P<0.01 by trend test) . The rate of missed diagnosis for not completely visible squamocolumnar junction (SCJ) was higher than that of the completely visible one (22.3% vs 2.1%; χ(2)=19.680, P<0.01) . The rate of missed diagnosis was higher for existing atypical vessels than those without (60.7% vs 10.6%; χ(2)=48.279, P<0.01) . The rate of missed diagnosis for visible lesion size ≥40 mm(2) was higher than that of <40 mm(2) (27.3% vs 4.2%; χ(2)=28.921, P<0.01) . The rate of missed diagnosis for the proportion of visible lesion size in ectocervical size ≥0.75 was higher than that of <0.75 (83.3% vs 14.1%; P<0.01) . The rate of missed diagnosis for the maximum linear length of visible lesion ≥10 mm was higher than that of <10 mm (46.9% vs 9.0%; χ(2)=44.473, P<0.01) . But the different severity of cervical cytology before colposcopy was not associated with missed ICUM (P>0.05) . Multivariable analysis found that visibility of SCJ, atypical vessels, visible lesion size and maximum linear length of visible lesion were associated with missed diagnosis of ICUM (all P<0.05) . Conclusions: The diagnostic value of HSIL by colposcopy is limited. Meanwhile, for the patients who are ≤50 years old with HSIL diagnosed by cervical biopsy, invisibility of SCJ, atypical vessels, visible lesion size and maximum linear length of visible lesion evaluated by colposcopy are the independent risk factors of missed ICUM. Thereby, it is necessary to take active intervention for HSIL with these risk factors.