Conization Research Articles

Use Trends and Recent Expenditures for Cervical Cancer Screening–Associated Services in Medicare Fee-for-Service Beneficiaries Older Than 65 Years

Since 1996, the US Preventive Services Task Force has recommended against cervical cancer screening in average-risk women 65 years or older with adequate prior screening. Little is known about the use of cervical cancer screening-associated services in this age group. To examine annual use trends in cervical cancer screening-associated services, specifically cytology and human papillomavirus (HPV) tests, colposcopy, and cervical procedures (loop electrosurgical excision procedure, cone biopsy, and ablation) in Medicare fee-for-service beneficiaries during January 1, 1999, to December 31, 2019, and estimate expenditures for services performed in 2019. This population-based, cross-sectional analysis included health service use data across 21 years for women aged 65 to 114 years with Medicare fee-for-service coverage (15-16 million women per year). Data analysis was conducted between July 2021 and April 2022. Proportion of testing modalities (cytology alone, cytology plus HPV testing [cotesting], HPV testing alone); annual use rate per 100 000 women of cytology and HPV testing, colposcopy, and cervical procedures from 1999 to 2019; Medicare expenditure for these services in 2019. There were 15 323 635 women 65 years and older with Medicare fee-for-service coverage in 1999 and 15 298 656 in 2019. In 2019, the mean (SD) age of study population was 76.2 (8.1) years, 5.1% were Hispanic, 0.5% were non-Hispanic American Indian/Alaska Native, 3.0% were non-Hispanic Asian/Pacific Islander, 7.4% were non-Hispanic Black, and 82.0% were non-Hispanic White. From 1999 to 2019, the percentage of women who received at least 1 cytology or HPV test decreased from 18.9% (2.9 million women) in 1999 to 8.5% (1.3 million women) in 2019, a reduction of 55.3%; use rates of colposcopy and cervical procedures decreased 43.2% and 64.4%, respectively. Trend analyses showed a 4.6% average annual reduction in use of cytology or HPV testing during 1999 to 2019 (P < .001). Use rates of colposcopy and cervical procedures decreased before 2015 then plateaued during 2015 to 2019. The total Medicare expenditure for all services rendered in 2019 was about $83.5 million. About 3% of women older than 80 years received at least 1 service at a cost of $7.4 million in 2019. The results of this cross-sectional study suggest that while annual use of cervical cancer screening-associated services in the Medicare fee-for-service population older than 65 years has decreased during the last 2 decades, more than 1.3 million women received these services in 2019 at substantial costs.

Risk Factors of Preterm Birth in Okinawa Prefecture, the Southernmost Island Prefecture of Japan.

A high rate of preterm birth has been reported in Okinawa Prefecture, the southernmost island prefecture of Japan. Hence, this study aimed to identify the risk factors for preterm birth in this prefecture. This retrospective study included data from January 2013 to December 2019 from three facilities in Okinawa Prefecture. Of 13,468 cases of preterm birth at ≥ 22 weeks of gestation, 11,868 were included in this study. Stillbirth and multiparity cases were excluded. First, we compared the overall preterm and full-term birth groups by categorizing the patient background, obstetric, and fetal risk factors. Further, we categorized preterm births into three groups (22-27, 28-33, and 34-36 weeks of gestation) and examined patient background factors to identify potential risk factors for the occurrence of preterm birth in each group. Preterm births accounted for 21.2% (2,521 cases) of all cases, with the rates of 2.6% (317 cases), 6.7% (800 cases), and 11.8% (1,404 cases) at 22-27, 28-33, and 34-36 weeks of gestation, respectively. To prevent preterm birth in Okinawa Prefecture, the present study specifically focused on patient background characteristics. In the multinomial logistic regression, the risk factors for preterm birth at 22-27 weeks of gestation were previous preterm birth (P < 0.0001) and lower age (P = 0.026); at 28-33 weeks of gestation, the risk factors were previous preterm birth (P < 0.0001) and history of cervical conization (P = 0.009); and at 34-36 weeks of gestation, only previous preterm birth (P < 0.0001) was a risk factor. Previous preterm birth, younger age, and history of cervical conization were risk factors for Preterm birth in Okinawa. To reduce premature births in Okinawa Prefecture, it is important to pick up women with these risk factors and provide them with appropriate guidance and education on an ongoing basis.

Prognostic Value of Human Papillomavirus Genotyping before and after Cervical Conization for Squamous Intraepithelial Lesion

Introduction: We previously reported that preoperative human papillomavirus (HPV) type 16/18 positivity and postoperative high-risk (HR)-HPV test positivity are associated with abnormal postoperative cytology. In this study, we further examined whether preoperative and postoperative HR-HPV genotyping could predict cytological abnormalities and the risk of additional surgery. Methods: Patients who underwent cervical conization at our hospital between July 2009 and June 2018 were enrolled. HPV genotyping was performed preoperatively for all patients with HPV-positive. The association among preoperative and postoperative HR-HPV genotyping results, the cumulative risk of cytological abnormalities, and additional surgery were evaluated. The endpoint approach was used to investigate the cumulative incidence of additional surgery owing to cytological abnormalities, such as low-grade squamous intraepithelial lesion positivity and recurrence 2 years after cervical conization. Results: Positive and negative histological margins were observed in 21 and 287 of 308 cases, respectively. The cumulative incidence of abnormal cytology and additional surgery was significantly higher in margin-positive cases than that in margin-negative cases. Examination established according to the margin status demonstrated that the postoperative HR-HPV-positive group had a significantly worse prognosis than the HR-HPV-negative group. Additionally, 32 cases, wherein the same genotype detected before and after surgery, demonstrated significantly unfavorable outcomes. Fifteen patients with persistent HPV 16/18 had the worst prognosis than the other types. Conclusion: Preoperative and postoperative HR-HPV genotype tests were used to predict the cumulative incidence of abnormal cytology and additional surgery. Particularly, patients with suspected persistent HPV type 16/18 infection are at a high recurrence risk.

Evaluation of the efficacy and safety of 5-aminolevulinic acid-mediated photodynamic therapy in women with high-risk HPV persistent infection after cervical conization

ObjectiveTo evaluate the efficacy and safety of photodynamic therapy (PDT) in women with high-risk human papillomavirus (hr-HPV) persistent infection after cervical conization, including loop electrosurgical excision procedure (LEEP) and cold knife conization (CKC). Materials and methodsThe clinicopathological and follow-up data of 76 women with hr-HPV persistent infection after cervical conization (54 cases with LEEP and 22 cases with CKC) were collected. All the women in this group met these criteria: postoperative pathological diagnosis of LEEP/CKC showed high grade squamous intraepithelial lesions (HSIL) with negative incisal margin, hr-HPV persistent infection after LEEP/CKC ≥ 1 year, colposcopy and histopathology showed no intraepithelial lesions before PDT, and 5-aminolaevulinic acid (5-ALA) as photosensitizer treating for 6 times with an interval of 7-10 days. The above patients were followed up 6 months and 12 months after PDT, and the follow-up contents included Roche Cobas HPV classification test, cytology, colposcopy, and pathological examinations. HPV negative conversion rate is an index to evaluate the efficacy of PDT. In addition, we also assessed the safety of PDT. ResultsSix months after PDT, the overall HPV clearance rate was 59.21% (45/76). The HPV negative conversion rates in patients ≤ 50 years old group and > 50 years old group were 68.52% (37/54) and 36.36% (8/22), respectively (P=0.009). But there was no significant difference in HPV clearance rate between the HPV16/18 infection group and other hr-HPV infection group (P=0.3326). 12 months after PDT, 1 case underwent hysterectomy because of progression to HSIL, and 7 cases lost follow-up. The overall HPV clearance rate was 88.24% (60/68). The negative conversion rates of HPV16/18 and other hr-HPV infection groups were 76.00% (19/25) and 95.35% (41/43), respectively (P=0.0458). However, the HPV negative conversion rate was not correlated with the patient's age (P=0.2383). The adverse reactions after PDT were mild, mainly manifested as increased vaginal secretions or burning/tingling. ConclusionsPhotodynamic therapy could be an effective treatment for patients with hr-HPV persistent infection after cervical conization and it could promote the negative conversion of hr-HPV and prevent the recurrence progression of cervical intraepithelial neoplasia (CIN) after LEEP/CKC.

Biology and management of lobular endocervical glandular hyperplasia.

Lobular endocervical glandular hyperplasia (LEGH) is a multicystic proliferative disorder of the uterine cervix. The aim of this review was to clarify the current understanding of this unique tumor. This article reviews the chronological progress of research regarding clinico-pathological and genetic aspects of LEGH and related cervical cystic diseases such as Nabothian cyst and adenocarcinoma of gastric type (GAS), using the literature and data from our institute. We also describe clinical management including preoperative diagnosis and adequate surgical/expectant treatment based on the biological features. Recent studies revealed several unique aspects of LEGH, that is, (i) production of gastric mucin, (ii) symptomatic and histological similarity with minimal deviation adenocarcinoma (MDA), and (iii) frequent association with GAS, including MDA. These findings indicated that LEGH is a gastric metaplasia, as well as pre-cancerous neoplasia. For the preoperative diagnosis of LEGH, the combination of "cosmos" sign on magnetic resonance imaging, detection of gastric mucin, and lack of nuclear atypia on cytology is important. Cone biopsy is effective for pathological diagnosis. Simple hysterectomy is indicated as surgical treatment for LEGH; however, meticulous follow-up is also an option, especially for young patients, because the rate of malignant transformation was reported to be 1%-2%. For LEGH patients who selected follow-up, a worsening cytology and increase in lesion size were important signs of malignant change of LEGH for safe follow-up. Proper understanding of the characteristics of LEGH is important for adequate management.

Cerclage in surgically shortened uterine cervix and pregnancy outcome: A retrospective comparison between the abdominal and vaginal procedures.

Cerclage for uterine cervical incompetence can be performed by the transabdominal or transvaginal approach. Transabdominal cerclage (TAC) is indicated for women with a short cervix or a cervical laceration who are inapplicable to transvaginal cerclage (TVC). The larger the volume of tissue removed in cervical conization, the greater the rate of miscarriage or preterm delivery in the subsequent pregnancy. The aim of this study was to compare TAC and TVC in post-cervical conization pregnancies. A retrospective, two-group, comparative study was conducted involving subjects who underwent cervical cerclage (TAC, n=14; TVC, n=18) following cervical conization and who were cared for at the University of Miyazaki Hospital between 2008 and 2020. We compared study subject characteristics and outcomes between the two groups. Primary outcome was incidence of preterm labor <37 weeks of gestation between the two groups. The preoperative median cervical length was significantly shorter in the TAC group (20.0 mm) than in the TVC group (31.0 mm; p < 0.01). Preoperative vaginal discharge cultures positive for Gardnerella showed a tendency to be greater in the TAC group (p=0.073). There was no significant difference in the preterm delivery rate < 37 weeks of gestation between TAC (1/14, 7.1%) and TVC (6/18, 33.3%) groups, p=0.10. Noninferiority test using multiple regression analysis showed that TAC is not inferior to TVC regarding gestational age at delivery, even though cervical length of TAC was significantly shorter. Women who were inapplicable to TVC due to a short cervix still achieved an equivalent outcome with TAC.

Prevalence of multiple human papillomavirus infections and association with cervical lesions among outpatients in Fujian, China: A cross-sectional study.

Multiple human papillomavirus (HPV) infections are common, but their impact on cervical lesions remains controversial. A total of 6225 female patients who underwent colposcopies/conization following abnormal cervical cancer screening results were included in the study. The final pathological diagnosis was determined by the most severe pathological grade among the cervical biopsy, endocervical curettage, and conization. Univariate and multivariate logistic regression analyses were used to investigate the association between multiple HPV infections and cervical lesions, adjusting for age, HPV genotype, gravidity and parity. In total, 33.3% (n = 2076) of the study population was infected with multiple HPV genotypes. Multiple HPV infections were more prevalent in patients younger than 25 years and older than 55 years, with the rate of multiple HPV infections at 52.8% and 44.3%, respectively. HPV16\52\18\58 are the most common HPV genotypes and usually appear as a single infection. Compared to single HR-HPV infection, multiple HR-HPV infections do not increase the risk of HSIL+, while single HR-HPV coinfected with LR-HPV seems to reduce the risk of HSIL+ (odds ratio = 0.515, confidence interval: 0.370-0.719, p < 0.001). Multiple HR-HPV infections cannot be risk-stratified for triage of HR-HPV-positive women.

Cervical conization before primary radical hysterectomy has a protective effect on disease recurrence in early cervical cancer: A two-center matched cohort study (174)

Objectives: Preoperative cervical conization, while reducing the cervical mass size, might decrease the chance of tumor spillage during surgery. This study aimed to ascertain whether cervical conization before primary radical hysterectomy (RH) has a protective effect in patients with early cervical cancer. Methods: We retrospectively identified node-negative, marginnegative, parametria-negative, 2009 FIGO stage IB1 cervical cancer patients who received primary Type C RH at two tertiary institutional hospitals between July 2006 and June 2020. Whether they received preoperative cervical conization or not, patients were divided into conization group (n=144) and control group (n=434). To adjust for confounders, we conducted a 1:1 propensity score matching for histology, surgical approach, lymphovascular space invasion, and cervical mass size (calculated by summing pathologic tumor size on conization and uterine specimens). Then, survival outcomes were compared between the matched groups. Results: Overall, the conization group had less cervical mass size and received minimally invasive surgery (MIS) more frequently (p=0.010) and adjuvant treatment less often (p=0.002) compared to the control group. Of 37 patients who received preoperative conization and had no residual tumor in the uterine specimen, only one (2.7%) recurred during 56.5 months of a median observation period. After matching, the conization group showed significantly better progression-free survival (PFS) than the control group (3-year: 94.2% vs 86.3%; p=0.012), whereas no significant difference in overall survival (OS) was found. Subgroup analysis in the open RH (n=91) revealed that PFS did not differ by preoperative conization (p=0.799). In contrast, in the MIS RH subgroup (n=197), preoperative conization was associated with significantly better PFS (p=0.005). Conclusions: Despite the retrospective design, our matched cohort study suggests that preoperative cervical conization might have a protective effect on disease recurrence in early cervical cancer, especially for those who are planning to undergo MIS RH. Further prospective studies are warranted. Objectives: Preoperative cervical conization, while reducing the cervical mass size, might decrease the chance of tumor spillage during surgery. This study aimed to ascertain whether cervical conization before primary radical hysterectomy (RH) has a protective effect in patients with early cervical cancer. Methods: We retrospectively identified node-negative, marginnegative, parametria-negative, 2009 FIGO stage IB1 cervical cancer patients who received primary Type C RH at two tertiary institutional hospitals between July 2006 and June 2020. Whether they received preoperative cervical conization or not, patients were divided into conization group (n=144) and control group (n=434). To adjust for confounders, we conducted a 1:1 propensity score matching for histology, surgical approach, lymphovascular space invasion, and cervical mass size (calculated by summing pathologic tumor size on conization and uterine specimens). Then, survival outcomes were compared between the matched groups. Results: Overall, the conization group had less cervical mass size and received minimally invasive surgery (MIS) more frequently (p=0.010) and adjuvant treatment less often (p=0.002) compared to the control group. Of 37 patients who received preoperative conization and had no residual tumor in the uterine specimen, only one (2.7%) recurred during 56.5 months of a median observation period. After matching, the conization group showed significantly better progression-free survival (PFS) than the control group (3-year: 94.2% vs 86.3%; p=0.012), whereas no significant difference in overall survival (OS) was found. Subgroup analysis in the open RH (n=91) revealed that PFS did not differ by preoperative conization (p=0.799). In contrast, in the MIS RH subgroup (n=197), preoperative conization was associated with significantly better PFS (p=0.005). Conclusions: Despite the retrospective design, our matched cohort study suggests that preoperative cervical conization might have a protective effect on disease recurrence in early cervical cancer, especially for those who are planning to undergo MIS RH. Further prospective studies are warranted.

The effect of cervical conization on women’s sexual function and psychological health (341)

Objectives: Diagnosis of cervical dysplasia and subsequent conization of the uterine cervix might affect women’s sexual health. The study objective was to assess the effect of cervical conization on women’s sexual function and psychological wellbeing using structured questionnaires. Methods: Patients undergoing conization of the cervix completed questionnaires before and 6-12 months after conization. Assessment of sexual distress and function was done using the female sexual distress scale-revised (FSDS-r) and the female sexual function inventory (FSFI), respectively. Risk for anxiety and depression was assessed using the Hospital Anxiety and Depression Scale (HADS). Results: From October 2018 to March 2021, 55 patients undergoing cervical conization were recruited. No significant differences were found in FSDS-r scores before and after conization. An equal number of patients indicated having sexual distress (29 patients, 53%, before and after conization, p=1.0). No significant changes were noticed on any FSDS domains or the total FSDS score before and after conization (26.8 vs 26.0, p=0.461). The percent of patients that indicated an overall sexual dysfunction, increased from 49 percent before conization, to 59 percent after conization (p=0.388). A high percentage of patients indicated signs of anxiety on the HADS questionnaire, both before and after conization (49% and 47%, respectively). The median anxiety and depression scores did not change after conization (p=1.0). Conclusions: A high percentage of patients undergoing conization suffer from sexual distress, sexual dysfunction, and general anxiety, both before and after conization. The conization procedure itself did not seem to affect questionnaire scores. Gynecologists should be aware of the psychological and sexual effects of the diagnosis and treatment of cervical pre-cancerous lesions; patients should be counseled accordingly. Objectives: Diagnosis of cervical dysplasia and subsequent conization of the uterine cervix might affect women’s sexual health. The study objective was to assess the effect of cervical conization on women’s sexual function and psychological wellbeing using structured questionnaires. Methods: Patients undergoing conization of the cervix completed questionnaires before and 6-12 months after conization. Assessment of sexual distress and function was done using the female sexual distress scale-revised (FSDS-r) and the female sexual function inventory (FSFI), respectively. Risk for anxiety and depression was assessed using the Hospital Anxiety and Depression Scale (HADS). Results: From October 2018 to March 2021, 55 patients undergoing cervical conization were recruited. No significant differences were found in FSDS-r scores before and after conization. An equal number of patients indicated having sexual distress (29 patients, 53%, before and after conization, p=1.0). No significant changes were noticed on any FSDS domains or the total FSDS score before and after conization (26.8 vs 26.0, p=0.461). The percent of patients that indicated an overall sexual dysfunction, increased from 49 percent before conization, to 59 percent after conization (p=0.388). A high percentage of patients indicated signs of anxiety on the HADS questionnaire, both before and after conization (49% and 47%, respectively). The median anxiety and depression scores did not change after conization (p=1.0). Conclusions: A high percentage of patients undergoing conization suffer from sexual distress, sexual dysfunction, and general anxiety, both before and after conization. The conization procedure itself did not seem to affect questionnaire scores. Gynecologists should be aware of the psychological and sexual effects of the diagnosis and treatment of cervical pre-cancerous lesions; patients should be counseled accordingly.

Robotic versus vaginal radical trachelectomy for reproductive-aged women with early cervical cancer: a multi-center Canadian study (097)

Robotic versus vaginal radical trachelectomy for reproductive-aged women with early cervical cancer: a multi-center Canadian study (097)

Clinical Diagnosis and Treatment Analysis of 16 Cases of Gastric-Type Endocervical Adenocarcinoma

Objective: Cervical cancer classification based on human papillomavirus (HPV) infection status is necessary, as the popularity of HPV vaccination is increasing. Hence, this study aimed to explore the clinicopathological features, diagnosis, treatment, and prognosis of gastric-type endocervical adenocarcinoma (GAS) in west China. Methods: We performed a retrospective analysis and follow-up of patients with GAS who were hospitalized in West China Second University Hospital, a tertiary care center in west China, between September 2019 and April 2021. Results: A total of 16 cases were pathologically diagnosed as GAS at the hospital, most of which had no specific clinical manifestations. Among the 16 cases, 3 cases were confirmed preoperatively. The occurrence of full-layer cervix stroma infiltration, lymphatic vessel infiltration, and lymph node metastasis were 87.5%, 100%, and 50%, respectively. Among all cases, 8 cases were classified as stage III according to the International Federation of Gynecology and Obstetrics 2018 Clinical Staging Standard for cervical cancer. A total of 15 patients underwent a transabdominal or laparoscopic extensive hysterectomy, and the remaining 1 patient was pathologically diagnosed with GAS after a total hysterectomy and afterward underwent bilateral oophorectomy and pelvic lymph node dissection as supplementary surgeries. The follow-up data presented the survival of the 16 patients receiving concurrent chemoradiotherapy after surgery. However, GAS recurred in 3 non-medically-controlled patients among the 16 patients in 3 to 6 months after the treatment. Conclusions: GAS is a rare but highly malignant cancer that usually results in a poor prognosis. A few reports of GAS diagnosis and treatment, especially from developing countries, are available. Hitherto clinical routine screening methods might be insufficient to fulfill the requirements of GAS diagnosis owing to the difficulties in preoperative diagnosis and the probability of misdiagnosis. To reduce the rate of misdiagnosis, repeated deep multisite biopsies, cervical curettage, cervical conization, and hysteroscopy might be helpful in suspicious GAS cases.

Combing pre-workshop, web-based learning and hands-on workshop as a flipped classroom clinical skill training model during the COVID-19 pandemic

ObjectiveDue to the COVID-19 pandemic, there is a dramatic drop in in-person residency training due to the implementation of isolation and triage measurements. Here, we propose a new flipped classroom clinical skill training model utilizing a combination of pre-workshop, web-based learning and hands-on workshop that shortens in-person contact time to maintain residency training during the pandemic. Effectiveness of this training model was evaluated with a pre-test and post-test skills competency assessment, two-way feedback, and a five-point Likert scale structured survey questionnaire. Materials and methodsThe workshop was conducted in a flipped classroom fashion by the obstetrics and gynecology (OBGYN) department of a single tertiary teaching medical center covering topics from five OBGYN subspecialities. Every topic consisted of a pre-workshop, web-based, mini lecture (PWML) followed by a hands-on workshop (HW). All first to fourth year OBGYN residents were invited to attend the workshop. All the trainees were required to complete the PWML prior to the day of HW. The workshop consisted of rotational station for each topic and was conducted within one afternoon. A 0-100-point scale pre-test and post-test skills competency evaluation were performed for each station and was assessed by the attending doctor or fellow doctor of each subspeciality. Two-way feedback was done after the post-test evaluation. A five-point Likert scale structured survey instrument consisting of participant’s perceptions of the workshop design, relevance to clinical practice, and quality of instructors and materials was created during the curriculum development process and sent to each participant one month after the workshop. ResultsA total of 19 residents including five first-year, six second-year, three third-year, and five fourth-year residents completed the entire pre-workshop lecture, workshop, pre-test, and post-test. For all residents, the average post-test score of 5 stations was 95 and was significantly higher than the pre-test score of 60 (p < 0.001). For both junior residents and senior residents, the average post-test scores of 5 stations were also significantly higher than pre-test scores (p < 0.001). Survey generated one month after the workshop showed a high overall satisfaction with the workshop instructors on their professional knowledge, communication skills, and interactions between the instructors and trainees. The average satisfaction scores for manipulation of vaginal breech delivery (VBD), semen analysis (SA), cervical conization (CC), obstetrics anal sphincter injury (OASIS), and laparoscopic suture techniques (LST) were 4.84, 4.96, 4.92, 4.88, and 4.92, respectively The average score for practical application of the training materials, class design and teaching method, overall satisfaction of the session, and time scheduling was 4.84, 4.96, 4.96, and 4.48, respectively. The entire HW was completed within 180 min and was carried out within half a day. ConclusionWith the implementation of isolation and triage measures in the COVID-19 pandemic, there is a dramatic drop in in-person exposure to all aspects of the residency training, in particular, non-emergent surgeries. Utilization of PWML saved 1/3 of in-person time and the entire workshop was completed within 180 min that could be carried out within half a day. The decrease of person-to-person contact time during the COVID-19 pandemic is necessary while still providing curriculum-based residency training in spite of decreased hands-on experience.

Performance of HPV E4 and p16INK4a biomarkers in predicting regression of cervical intraepithelial neoplasia grade 2 (CIN2): protocol for a historical cohort study

IntroductionCervical intraepithelial neoplasia grade 2 (CIN2) represents a spectrum of lesions with variable progression and regression. Pathological diagnosis of CIN2 is subjective and poorly reproducible. Accurate diagnosis and identification of...

Analysis of the Clinical Value of MAGE-A9 Expressions in Cervical Cancer Tissues and PBMC.

Objective The aim of this study is to explore the expressions and clinical significance of melanoma-associated antigen-A9 (MAGE-A9) in cervical cancer tissues and peripheral blood mononuclear cells (PBMC). Methods 108 patients who were scheduled to undergo cervical conization or extensive hysterectomy between March 2019 and January 2021 due to cervical lesions were selected by convenient sampling. According to postoperative pathological results, the patients were divided into a cervical cancer group (n = 64) and cervical intraepithelial neoplasia (CIN) group (n = 44). The expression levels of MAGE-A9 mRNA in cervical lesion tissues and PBMC were detected by real-time fluorescence quantitative PCR, and the expression of MAGE-A9 protein in lesion tissues was detected by immunohistochemistry. The correlation between MAGE-A9 mRNA expressions in cancer tissues and PBMC and serum tumor markers in patients with cervical cancer and the relationship between MAGE-A9 protein expression in cancer tissues and clinicopathological characteristics were analyzed, and a receiver operating characteristic curve (ROC curve) was drawn to explore the diagnostic value of MAGE-A9 mRNA expressions in cancer tissues and PBMC on cervical cancer. Results The expression levels of MAGE-A9 mRNA in cervical lesion tissues and PBMC in the cervical cancer group were significantly higher than those in the CIN group (P < 0.05), and the levels of serum SCC-Ag, CA-125, and CEA were significantly higher than those in the CIN group (P < 0.05). The positive rate of the MAGE-A9 protein expression in cervical lesion tissues in the cervical cancer group was significantly higher than that in the CIN group (P < 0.05). The expression levels of MAGE-A9 mRNA in cancer tissues and PBMC of patients with cervical cancer were positively correlated with serum SCC-Ag, CA-125, and CEA (P < 0.05). The positive rate of the MAGE-A9 protein expression in cervical cancer tissues was related to FIGO stage, tumor diameter, degree of differentiation, lymph node metastasis, and high-risk HPV infection (P < 0.05) and was not correlated with age and pathological type (P > 0.05). The areas under the ROC curves of MAGE-A9 mRNA in lesion tissue and MAGE-A9 mRNA in PBMC were 0.925 and 0.900 in the diagnosis of cervical cancer (P < 0.05). Conclusion The expressions of MAGE-A9 in cancer tissues and PBMC of patients with cervical cancer are upregulated, which is related to the levels of serum tumor markers and the progression of disease. MAGE-A9 is expected to become an important marker for the diagnosis of early cervical cancer.

Global guidelines for cervical cancer and precancerous lesions treatment: a systematic review

Objective: To systematically summarize current status and recommendations of the global cervical cancer and precancerous lesions treatment guidelines. Methods: The retrieval for all the Chinese and English literature published before July 8, 2021 was conducted in PubMed, Embase, SinoMed Database, CNKI and Wanfang Database, supplemented by a search of health websites of countries worldwide, with"uterine cervical neoplasms""cervix cancer""cervical neoplasm""cervical precancerous lesions""treat*""guideline*""practice guideline*""consensus" "recommendation*""guidebook*"in English as well as"cervical precancerous lesions""cervical neoplasm""treatment""guideline*""consensus"in Chinese as search keywords. A total of 38 guidelines were included for data extraction and analysis. Results: Guidelines covered Asia, Europe, North America, South America and Oceania. Conservative observation was recommended for the CIN1 population. For the women with CIN2/CIN3, ablation or excision was recommended according to the specific situation and guidelines of developed countries give priority to the latter. In low and middle resource countries, given the availability of medical resources, ablative treatment was recommended as an alternative to excisional treatment if the women were eligible. For women with adenocarcinoma in situ (AIS), cervical conization or total hysterectomy was recommended depending on the patient's desire of fertility. For patients with cervical cancer, most guidelines recommended surgery for early disease and smaller lesions, otherwise concurrent chemoradiotherapy was usually the main treatment modality for advanced cancers. All guidelines recommended long-term follow-up to monitor disease recurrence after treatment. Follow-up methods included human papillomavirus (HPV) testing and/or cytology or colposcopy. Most guidelines recommended follow-up at 6 or 12 months after treatment for cervical precancerous lesions, and 3~4 months for cervical cancer. Conclusions: There are some differences in the treatment and management recommendations for cervical cancer and precancerous lesions issued by different countries and regions around the world. Based on the global treatment guidelines and medical resource of different regions, the treatment and management guidelines for cervical cancer and precancerous lesions suitable for different regions of China should be developed, so as to achieve effective treatment.

Is Endocervical Glandular Involvement Related to The Depth of Cone Biopsy?

Introduction. This study aimed to determine whether endocervical glandular involvement by squamous intraepithelial lesion would differ with respect to the depth of the excised specimen and analyze the related factors that may define endocervical glandular involvement among cases treated with cone biopsy. Methods. Between April 2016 and December 2018, women who underwent colposcopy and excisional procedures in the department of gynecologic oncology were retrospectively investigated. Patients with multiple specimens, or whose specimen depths were not measured, and a negative/unknown HPV status were excluded from the study. Also, patients with no dysplasia or microinvasive/invasive cancer in the final pathology report and those who had not undergone endocervical curettage during colposcopy were excluded. HPV genotypes, degree of dysplasia, surgical margin status, and specimen depth were documented from medical records. Further, the association of these factors with endocervical glandular involvement was evaluated. Results: A total of 321 patients who fulfilled the criteria were included in the study, with a mean age of 41.9 years. In total, 101 patients (31.5%) had endocervical glandular involvement. The mean excised specimen depth was 17.04 mm; 17.9 and 16.7 mm for the positive and negative glandular involvement groups, respectively (p = .13). The mean ages were 42.7 and 41.6 years for these groups, respectively (p = .32). There was no association between the HPV genotypes and glandular involvement. Conclusions: Endocervical glandular involvement is not associated with the depth of the excised specimen. A deeper cone biopsy may not necessarily enable a more effective treatment of the disease.

Modified method of cervical conization with hybrid use of a cold knife and an electric knife for high-grade squamous intraepithelial lesions.

ObjectiveTo evaluate the feasibility and surgical outcome of the modified method of cervical conization with hybrid use of a cold knife and an electric knife.MethodsA retrospective analysis of cervical conization for high-grade squamous intraepithelial lesions was performed between January 2020 and December 2020. Traditional cold knife conization and modified conization were used. The clinical characteristics and surgical outcomes were compared between these methods.ResultsNinety-two patients with high-grade squamous intraepithelial lesions were included. Traditional conization was performed in 46 patients, and the modified method was used in 46 patients. There were no differences in clinical characteristics, such as age, menopausal status, and conization height, between the methods. Intraoperative blood loss with the modified method was significantly lower than that with traditional conization (27.6 ± 4.7 vs 51.3 ± 18.3 mL). Postoperative vaginal bleeding requiring emergent measures, such as prolonged gauze compression, sutures, or electrocautery, was significantly less with the modified method than with traditional conization (4.3% vs 17.4%). A median follow-up of 10.2 months showed no significant difference in persistence or recurrence between the methods.ConclusionsThe modified method of cervical conization with hybrid use of cold and electric knives may be a good alternative to traditional cold knife conization.

Healthcare Costs and Resource Use Associated With Cervical Intraepithelial Neoplasia and Cervical Conization: A Retrospective Study of German Statutory Health Insurance Claims Data

Background: Cervical intraepithelial neoplasia (CIN) can be a consequence of human papillomavirus (HPV) infection. High-grade CIN (CIN2/CIN3) may develop from persistent HPV infection and progress to cervical cancer if left untreated. Management of CIN includes conservative surveillance or ablation and excision by conization. Internationally, CIN and its treatment generate a considerable economic burden, but no current data regarding costs and resource use from the perspective of the German statutory health insurance exist. Objectives: The aim of this study was to explore the health economic burden in women with CIN diagnoses who either underwent cervical conization or were managed conservatively. Methods: We conducted a retrospective claims data analysis using the InGef Research Database from 2013 to 2018. Healthcare costs and resource utilization in a 24-month observation period (1:1:1 matching) were compared in 18- to 45-year-old women with CIN (1-3) who underwent a conization procedure (study cohort 1) and in women with CIN (1-3) who did not undergo conization (study cohort 2) to women with neither CIN nor conization (control group). Results: For each group, 2749 women were identified. Mean total healthcare costs after 24 months were higher in study cohort 1 (€4446, _P_&lt;.01) and study cohort 2 (€3754, _P_=.09) compared with the control group (€3426). Comparing study cohort 1 and 2 to controls, mean differences were highest in age groups 41-45 years (cohort 1: €5115 vs €3354, _P_&lt;.01; cohort 2: €4152 vs €3354, _P_=.14). Significantly more women were hospitalized at least once in study cohort 1 (57.46%, _P_&lt;.01) and study cohort 2 (38.74%, _P_&lt;.01) compared with the control group (31.14%). Frequency of outpatient physician visits was significantly higher in both study cohorts (43.23 visits, P&lt;.01 and 38.60 visits, _P_&lt;.01) compared with the control group (32.07 visits). Conclusion: Our results revealed 30% and 10% increased total healthcare costs in women with CIN undergoing invasive treatment (study cohort 1) and conservative management (study cohort 2), respectively, compared with a control group of women with no CIN in a 2-year follow-up period.

Healthcare Costs and Resource Use Associated With Cervical Intraepithelial Neoplasia and Cervical Conization: A Retrospective Study of German Statutory Health Insurance Claims Data

Background: Cervical intraepithelial neoplasia (CIN) can be a consequence of human papillomavirus (HPV) infection. High-grade CIN (CIN2/CIN3) may develop from persistent HPV infection and progress to cervical cancer if left untreated. Management of CIN includes conservative surveillance or ablation and excision by conization. Internationally, CIN and its treatment generate a considerable economic burden, but no current data regarding costs and resource use from the perspective of the German statutory health insurance exist. Objectives: The aim of this study was to explore the health economic burden in women with CIN diagnoses who either underwent cervical conization or were managed conservatively. Methods: We conducted a retrospective claims data analysis using the InGef Research Database from 2013 to 2018. Healthcare costs and resource utilization in a 24-month observation period (1:1:1 matching) were compared in 18- to 45-year-old women with CIN (1-3) who underwent a conization procedure (study cohort 1) and in women with CIN (1-3) who did not undergo conization (study cohort 2) to women with neither CIN nor conization (control group). Results: For each group, 2749 women were identified. Mean total healthcare costs after 24 months were higher in study cohort 1 (€4446, P&lt;.01) and study cohort 2 (€3754, P=.09) compared with the control group (€3426). Comparing study cohort 1 and 2 to controls, mean differences were highest in age groups 41-45 years (cohort 1: €5115 vs €3354, P&lt;.01; cohort 2: €4152 vs €3354, P=.14). Significantly more women were hospitalized at least once in study cohort 1 (57.46%, P&lt;.01) and study cohort 2 (38.74%, P&lt;.01) compared with the control group (31.14%). Frequency of outpatient physician visits was significantly higher in both study cohorts (43.23 visits, P&lt;.01 and 38.60 visits, P&lt;.01) compared with the control group (32.07 visits). Conclusion: Our results revealed 30% and 10% increased total healthcare costs in women with CIN undergoing invasive treatment (study cohort 1) and conservative management (study cohort 2), respectively, compared with a control group of women with no CIN in a 2-year follow-up period.

Healthcare Costs and Resource Use Associated With Cervical Intraepithelial Neoplasia and Cervical Conization: A Retrospective Study of German Statutory Health Insurance Claims Data.

Background: Cervical intraepithelial neoplasia (CIN) can be a consequence of human papillomavirus (HPV) infection. High-grade CIN (CIN2/CIN3) may develop from persistent HPV infection and progress to cervical cancer if left untreated. Management of CIN includes conservative surveillance or ablation and excision by conization. Internationally, CIN and its treatment generate a considerable economic burden, but no current data regarding costs and resource use from the perspective of the German statutory health insurance exist. Objectives: The aim of this study was to explore the health economic burden in women with CIN diagnoses who either underwent cervical conization or were managed conservatively. Methods: We conducted a retrospective claims data analysis using the InGef Research Database from 2013 to 2018. Healthcare costs and resource utilization in a 24-month observation period (1:1:1 matching) were compared in 18- to 45-year-old women with CIN (1-3) who underwent a conization procedure (study cohort 1) and in women with CIN (1-3) who did not undergo conization (study cohort 2) to women with neither CIN nor conization (control group). Results: For each group, 2749 women were identified. Mean total healthcare costs after 24 months were higher in study cohort 1 (€4446, P<.01) and study cohort 2 (€3754, P=.09) compared with the control group (€3426). Comparing study cohort 1 and 2 to controls, mean differences were highest in age groups 41-45 years (cohort 1: €5115 vs €3354, P<.01; cohort 2: €4152 vs €3354, P=.14). Significantly more women were hospitalized at least once in study cohort 1 (57.46%, P<.01) and study cohort 2 (38.74%, P<.01) compared with the control group (31.14%). Frequency of outpatient physician visits was significantly higher in both study cohorts (43.23 visits, P<.01 and 38.60 visits, P<.01) compared with the control group (32.07 visits). Conclusion: Our results revealed 30% and 10% increased total healthcare costs in women with CIN undergoing invasive treatment (study cohort 1) and conservative management (study cohort 2), respectively, compared with a control group of women with no CIN in a 2-year follow-up period.