Optimal Dietary Intake of Riboflavin Associated with Lower Risk of Cervical Cancer in Korea: Korean National Health and Nutrition Examination Survey 2010-2021.

BACKGROUND: This study aimed to evaluate the association between the dietary intake of vitamin B complex (thiamine, riboflavin, and niacin) and cervical cancer in Korea. METHODS: The data from the Korean National Health and Nutrition Examination Survey (KNHANES) from 2010 to 2021 were analyzed, which included 28,306 participants who were categorized into non-cervical cancer and cervical cancer groups. The following dietary intake threshold levels of thiamine, riboflavin, and niacin were identified based on the recommended daily allowances (RDAs): thiamine, 1.1 mg/day; riboflavin, 1.2 mg/day; and niacin, 14 mg/day. RESULTS: Among 28,306 participants, 27,976 were in the non-cervical cancer group and 330 were in the cervical cancer group. Riboflavin intakes of more than 1.2 mg/day but less than 2.4 mg/day were associated with a significantly reduced risk of cervical cancer, whereas intakes of above 2.4 mg/day were not associated with cervical cancer. Thiamine and niacin intakes were not significantly related to the risk of cervical cancer. CONCLUSIONS: The results of this study suggest that an intake of riboflavin of 1.2-2.4 mg/day may contribute to a lower risk of cervical cancer.

Enhancing Cervical Cancer Screening: Review of p16/Ki-67 Dual Staining as a Promising Triage Strategy.

Cervical cancer, primarily caused by high-risk human papillomavirus (HR-HPV) types 16 and 18, is a major global health concern. Persistent HR-HPV infection can progress from reversible precancerous lesions to invasive cervical cancer, which is driven by the oncogenic activity of human papillomavirus (HPV) genes, particularly E6 and E7. Traditional screening methods, including cytology and HPV testing, have limited sensitivity and specificity. This review explores the application of p16/Ki-67 dual-staining cytology for cervical cancer screening. This advanced immunocytochemical method allows for simultaneously detecting p16 and Ki-67 proteins within cervical epithelial cells, offering a more specific approach for triaging HPV-positive women. Dual staining and traditional methods are compared, demonstrating their high sensitivity and negative predictive value but low specificity. The increased sensitivity of dual staining results in higher detection rates of CIN2+ lesions, which is crucial for preventing cervical cancer progression. However, its low specificity may lead to increased false-positive results and unnecessary biopsies. The implications of integrating dual staining into contemporary screening strategies, particularly considering the evolving landscape of HPV vaccination and changes in HPV genotype prevalence, are also discussed. New guidelines and further research are necessary to elucidate the long-term effects of integrating dual staining into screening protocols.

Depressed Mood as a Significant Risk Factor for Gynecological Cancer Aggravation.

BACKGROUND: The aim of this study was to evaluate the relationship between depressed mood and gynecological cancer outcomes, identifying risk factors for cancer aggravation. METHODS: This study was a retrospective analysis of gynecological cancer patients (January 2020-August 2022) at Korea University Anam Hospital using Patient Health Questionnaire-9 (PHQ-9). Patients were classified into non-depressed mood (NDM)- and depressed mood (DM)-based scores. Statistical analysis was performed using Student's t-test, chi-square test, Fisher's exact test, Kaplan-Meier analysis, and Cox regression analyzing using SPSS. RESULTS: Of the 217 participants, the NDM group comprised 129 patients, and the DM group comprised 88. The two-year disease-free survival (DFS) rates showed significant differences (NDM, 93.6%; DM 86.4%; p = 0.006), but overall survival (OS) did not (p = 0.128). Patients with stage 3 or higher cancer, undergoing five or more chemotherapies, experiencing post-chemotherapy side effects, and depressed mood had an increased risk of cancer aggravation. CONCLUSIONS: Appropriate treatment of depressed mood, as well as adequate treatment for advanced gynecological cancer patients, those with numerous CTx., and those with post-CTx. side effects, may contribute to reducing the risk of cancer aggravation.

Pivotal Clinical Study to Evaluate the Efficacy and Safety of Assistive Artificial Intelligence-Based Software for Cervical Cancer Diagnosis.

Colposcopy is the gold standard diagnostic tool for identifying cervical lesions. However, the accuracy of colposcopies depends on the proficiency of the colposcopist. Machine learning algorithms using an artificial intelligence (AI) system can quickly process large amounts of data and have been successfully applied in several clinical situations. This study evaluated the feasibility of an AI system as an assistive tool for diagnosing high-grade cervical intraepithelial neoplasia lesions compared to the human interpretation of cervical images. This two-centered, crossover, double-blind, randomized controlled trial included 886 randomly selected images. Four colposcopists (two proficient and two inexperienced) independently evaluated cervical images, once with and the other time without the aid of the Cerviray AI® system (AIDOT, Seoul, Republic of Korea). The AI aid demonstrated improved areas under the curve on the localization receiver-operating characteristic curve compared with the colposcopy impressions of colposcopists (difference 0.12, 95% confidence interval, 0.10-0.14, p < 0.001). Sensitivity and specificity also improved when using the AI system (89.18% vs. 71.33%; p < 0.001, 96.68% vs. 92.16%; p < 0.001, respectively). Additionally, the classification accuracy rate improved with the aid of AI (86.40% vs. 75.45%; p < 0.001). Overall, the AI system could be used as an assistive diagnostic tool for both proficient and inexperienced colposcopists in cervical cancer screenings to estimate the impression and location of pathologic lesions. Further utilization of this system could help inexperienced colposcopists confirm where to perform a biopsy to diagnose high-grade lesions.

Trends in Gynecologic Carcinosarcoma Based on Analysis of the Surveillance Epidemiology End Result (SEER) Database.

Carcinosarcomas (malignant mixed Mullerian tumors) of a female genital organ are rare tumors associated with a poor survival. The purpose of this study was to identify site-specific differences in the incidence and prognosis in carcinosarcomas originating in the uterus, cervix, or ovary. The data of patients with gynecologic carcinosarcomas were extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2016. The characteristics of gynecologic carcinosarcomas were compared using Pearson X2 and Fisher's exact tests. Kaplan-Meier models were used for cause-specific survival (CSS) analysis. The cohort included 7086 females, including 5731 cases of uterine carcinosarcoma, 161 cervical carcinosarcomas, and 1193 ovarian carcinosarcomas. The age-adjusted incidence rates of uterine, cervical, and ovarian carcinosarcoma were 3.9, 0.1, and 0.6 per 1,000,000, respectively. In the distribution of carcinosarcoma incidence by race, compared with the uterus or cervix, those originating from the ovary were unequally distributed in Caucasians (84.4% versus 69.6%, 67.7%; p < 0.001). The incidence of uterine carcinosarcoma steadily increased over time, from 2.2 in 2000 to 5.5 in 2016 (per 1,000,000), while cervical or ovarian carcinosarcoma showed no significant difference in incidence. The five-year CSS rates based on the site of origin (uterus, cervix, and ovary) were 39.9%, 33.1%, and 25.8%, respectively. The incidence rates of gynecologic carcinosarcoma, especially uterine carcinosarcoma, are gradually increasing. Although uterine carcinosarcoma is associated with a higher incidence than the others, it has a better prognosis compared with ovarian and cervical carcinosarcoma. The survival rates were worst in ovarian carcinosarcoma.

Comparison of Surgical Outcomes between Single-Port Laparoscopic Surgery and Da Vinci Single-Port Robotic Surgery.

BACKGROUND: The aim of this study is to compare the surgical outcomes of single-port laparoscopic surgery (SPLS) and single-port robotic surgery (SPRS). METHODS: We retrospectively analyzed patients who underwent a hysterectomy, ovarian cystectomy, or myomectomy with SPLS or SPRS from January 2020 to July 2022. Statistical analyses were performed using the SPSS chi-square test and student's t-test. RESULTS: A total of 566 surgeries including single-port laparoscopic hysterectomy (SPLH; n = 148), single-port robotic hysterectomy (SPRH; n = 35), single-port laparoscopic ovarian cystectomy (SPLC; n = 207), single-port robotic ovarian cystectomy (SPRC; n = 108), single-port laparoscopic myomectomy (SPLM; n = 12), and single-port robotic myomectomy (SPRM; n = 56). The SPRH, SPRC, and SPRM groups had a shorter operation time than the SPLS group, although the results were not statistically significant (SPRH vs. SPLH, p = 0.134; SPRC vs. SPLC, p = 0.098; SPRM vs. SPLM, p = 0.202). Incisional hernia occurred as a postoperative complication in two patients only in the SPLH group. Postoperative Hb changes were lower in the SPRC and SPRM groups than in the SPLC and SPLM groups (SPRC vs. SPLC, p = 0.023; SPRM vs. SPLM, p = 0.010). CONCLUSIONS: Our study demonstrated that the SPRS had comparable surgical outcomes when compared to the SPLS. Therefore, the SPRS should be considered a feasible and safe option for gynecologic patients.

Application of Immune Checkpoint Inhibitors in Gynecological Cancers: What Do Gynecologists Need to Know before Using Immune Checkpoint Inhibitors?

Standard treatments for gynecological cancers include surgery, chemotherapy, and radiation therapy. However, there are limitations associated with the chemotherapeutic drugs used to treat advanced and recurrent gynecological cancers, and it is difficult to identify additional treatments. Therefore, immune checkpoint inhibitor (ICI) therapy products, including PD-1/PD-L1 inhibitors and CTLA-4 inhibitors, are in the spotlight as alternatives for the treatment of advanced gynecological cancers. Although the ICI monotherapy response rate in gynecological cancers is lower than that in melanoma or non-small cell lung cancer, the response rates are approximately 13-52%, 7-22%, and 4-17% for endometrial, ovarian, and cervical cancers, respectively. Several studies are being conducted to compare the outcomes of combining ICI therapy with chemotherapy, radiation therapy, and antiangiogenesis agents. Therefore, it is critical to determine the mechanism underlying ICI therapy-mediated anti-tumor activity and its application in gynecological cancers. Additionally, understanding the possible immune-related adverse events induced post-immunotherapy, as well as the appropriate management of diagnosis and treatment, are necessary to create a quality environment for immunotherapy in patients with gynecological cancers. Therefore, in this review, we summarize the ICI mechanisms, ICIs applied to gynecological cancers, and appropriate diagnosis and treatment of immune-related side effects to help gynecologists treat gynecological cancers using immunotherapy.

Factors associated with cervical cancer screening behaviors among young married female (aged 20-29) immigrants in South Korea.

OBJECTIVE: To identify factors that affect the participation of female immigrants in their 20s in the national cervical cancer screening programs. METHODS: Data were obtained from the National Health Insurance Services from 2016 to 2017. A total of 17,730 women who agreed to undergo cervical cancer screening during 2016-2017 were included in the study. RESULTS: Of the 17,730 women, 8,149 (46%) participated in cervical cancer screening, whereas, 9,581 (54%) did not. Logistic regression analysis of factors related to cervical cancer screening showed that the odds ratio (OR) of screening was higher in short duration of stay (OR, 1.18; 95% confidence interval [CI], 1.03-1.35), Chinese nationality (OR, 1.43; 95% CI, 1.28-1.59), unemployment (OR, 1; 95% CI, reference), participation in general health screening (OR, 4.16; 95% CI, 3.24-5.33), and comorbidities (OR, 1.16; 95% CI, 1.09-1.24) when compared to the other populations. The highest OR was associated with participation in general health screening. CONCLUSION: Appropriate programs should be developed to increase participation of socially vulnerable groups in cervical cancer screening. Such programs will improve awareness regarding cervical cancer screening and reduce disparities in healthcare.

The necessity of continuing cervical cancer screening of elderly Korean women aged 65 years or older.

BACKGROUND: Although the incidence of cervical cancer has decreased since the 1980s in Korea, it remains high among the elderly women. This study evaluated the suitability of cervical cancer screening for elderly Korean women aged ≥65 years according to recommendations by the American Society of Cytopathology and American Society for Colposcopy and Cervical Pathology. METHODS: We retrospectively reviewed the records of patients who underwent cervical cancer screening, followed by liquid-based Pap test, human papillomavirus (HPV) test, and colposcopic punch biopsy at two academic hospitals from May 2008 to May 2018. The participants were divided into two groups <65 and ≥65 years old. Logistic regression analysis was performed to evaluate the association between cytology tests, HPV tests and the occurrence of high-risk lesions, ≥cervical intraepithelial neoplasia2 (CIN2). RESULTS: The mean patient age was 49.02 ± 15.437 (range 15-91) years. No patients aged <25 years showed atypical squamous cell-cannot exclude high grade (ASC-H), squamous cell carcinoma (SCC), or adenocarcinoma (ADC). The incidence of high-grade squamous intraepithelial lesion (HISL) (39.7%) and ≥CIN 3 (40.2%) was significantly higher in patients ≥65 years of age than in other age groups. However, patients ≥65 years showed increased HSIL and HPV negativity and ASC-H, HSIL, and HPV positivity in those with ≥CIN 2 (both p = .043). CONCLUSION: Korean women aged ≥65 years should undergo cervical cancer screening. The relevance of HPV or Cytology test alone or co-test for screening should be evaluated in this population.

Analysis of the Relationship between Socioeconomic Status and Incidence of Hysterectomy Using Data of the Korean Genome and Epidemiology Study (KoGES).

Hysterectomy remains a frequent gynecologic surgery, although its rates have been decreasing. The aim of this study was to investigate whether socioeconomic status affected the risk of hysterectomy in Korean women. This prospective cohort study used epidemiologic data from 2001 to 2016, from the Korean Genomic and Epidemiology Study (KoGES). Multivariate logistic regression analyses were performed to estimate the association between household income or education level and hysterectomy. Among 5272 Korean women aged 40−69 years, 720 who had a hysterectomy and 4552 controls were selected. Variable factors were adjusted using logistic regression analysis (adjusted model). Adjusted odds ratios (aORs) for insurance type and hysterectomy were not statistically significant. The aOR was 1.479 (95% confidence interval (CI): 1.018−2.146, p < 0.05) for women with education of high school or lower compared to college or higher. Women whose monthly household income was

Role of Artificial Intelligence Interpretation of Colposcopic Images in Cervical Cancer Screening.

The accuracy of colposcopic diagnosis depends on the skill and proficiency of physicians. This study evaluated the feasibility of interpreting colposcopic images with the assistance of artificial intelligence (AI) for the diagnosis of high-grade cervical intraepithelial lesions. This study included female patients who underwent colposcopy-guided biopsy in 2020 at two institutions in the Republic of Korea. Two experienced colposcopists reviewed all images separately. The Cerviray AI® system (AIDOT, Seoul, Korea) was used to interpret the cervical images. AI demonstrated improved sensitivity with comparable specificity and positive predictive value when compared with the colposcopic impressions of each clinician. The areas under the curve were greater with combined impressions (both AI and that of the two colposcopists) of high-grade lesions, when compared with the individual impressions of each colposcopist. This study highlights the feasibility of the application of an AI system in cervical cancer screening. AI interpretation can be utilized as an assisting tool in combination with human colposcopic evaluation of exocervix.

Learning curve could affect oncologic outcome of minimally invasive radical hysterectomy for cervical cancer.

BACKGROUND/OBJECTIVE: Recent prospective studies have shown poorer oncologic outcomes following minimally invasive surgery, which has led many surgeons to deeply inspect their practices. We reviewed our experience and evaluated the results of radical hysterectomy in patients with early stage cervical cancer. METHODS: This retrospective study included patients with early stage cervical cancer (Ia1 - IIa1) who were treated with radical hysterectomy from May 2006 to Dec 2016. Patients were divided into three groups according to the surgical approach: radical abdominal hysterectomy (RAH), laparoscopic radical hysterectomy (LRH), and robot-assisted radical hysterectomy (RRH). RESULTS: Learning curves of each type of surgery were obtained using the cumulative sum method. Survival rates were compared using Kaplan-Meier curves. To analyze the learning curve of a single surgeon, 89 patients were selected from the whole population. Learning curves of each group showed two distinct phases. The minimum number of cases required to achieve surgical improvement were 16 in RAH, 13 in LRH, and 21 in RRH. Progression-free survival (PFS) and overall survival did not vary between RAH and minimally invasive surgery (MIS) (p = .828 and p = .757, respectively). However, when stratified by the phases of the learning curves, patients included in the early phase of MIS showed a poorer PFS (p = .014). CONCLUSIONS: Surgical proficiency could significantly affect the oncologic outcome in MIS. A prospective study regarding sufficient surgical competence is necessary for elaborate analysis of the feasibility of minimally invasive radical hysterectomy.

Advances in the Treatment and Prevention of Chemotherapy-Induced Ovarian Toxicity.

Due to improvements in chemotherapeutic agents, cancer treatment efficacy and cancer patient survival rates have greatly improved, but unfortunately gonadal damage remains a major complication. Gonadotoxic chemotherapy, including alkylating agents during reproductive age, can lead to iatrogenic premature ovarian insufficiency (POI), and loss of fertility. In recent years, the demand for fertility preservation has increased dramatically among female cancer patients. Currently, embryo and oocyte cryopreservation are the only established options for fertility preservation in women. However, there is growing evidence for other experimental techniques including ovarian tissue cryopreservation, oocyte in vitro maturation, artificial ovaries, stem cell technologies, and ovarian suppression. To prevent fertility loss in women with cancer, individualized fertility preservation options including established and experimental techniques that take into consideration the patient's age, marital status, chemotherapy regimen, and the possibility of treatment delay should be provided. In addition, effective multidisciplinary oncofertility strategies that involve a highly skilled and experienced oncofertility team consisting of medical oncologists, gynecologists, reproductive biologists, surgical oncologists, patient care coordinators, and research scientists are necessary to provide cancer patients with high-quality care.

Risk factors for type-specific persistence of high-risk human papillomavirus and residual/recurrent cervical intraepithelial neoplasia after surgical treatment.

OBJECTIVE: This study aimed to investigate the clinicopathologic risk factors for type-specific persistence of high-risk human papillomavirus (hrHPV) and residual/recurrent cervical intraepithelial neoplasia (CIN) after surgical treatment. METHODS: Patients with CIN-2/3 who underwent conization or loop electrosurgical excision procedure (LEEP) at Korea University Hospital were enrolled. All patients underwent hrHPV testing and genotyping before conization or LEEP followed by both hrHPV genotyping and cytology. The significance of associations between patient characteristics and persistence of infection were assessed by multivariate logistic regression analyses. RESULTS: Among 398 women with pathologically confirmed CIN-2/3, 154 (38.7%) patients showed hrHPV persistence after surgical treatment. In multivariate analysis, high preoperative hrHPV load (P<0.05; odds ratio [OR], 2.063), presence of CIN-2 at treatment (P<0.01; OR, 2.732), and multiple hrHPV infections (P<0.001; OR, 4.752) were associated with hrHPV persistence. HPV 53 was the most likely to persist after treatment (24/43, 55.8%). The risk of residual/recurrent CIN-2/3 was higher in persistent infection with HPV 16 than other types (P<0.05). Menopause (P<0.001; OR, 3.969), preoperative and postoperative hrHPV load (P<0.05; OR, 2.430; P<0.05; OR, 5.351), and infection with multiple hrHPV types (P<0.05; OR, 2.345) were significantly related to residual/recurrent CIN following surgical treatment. CONCLUSION: HPV load before treatment and infection with multiple hrHPV types were predictors of postoperative hrHPV persistence. HPV 53 was the type most likely to persist, but HPV 16 was the type that was most closely associated with residual/recurrent CIN-2/3.

Comparing efficacy of high-dose rate brachytherapy versus helical tomotherapy in the treatment of cervical cancer.

OBJECTIVE: Boost radiation using brachytherapy (BT) is a standard treatment for local disease control in concomitant chemoradiation therapy (CCRT) for advanced cervical cancer. However, it is associated with gastrointestinal and genitourinary complications. Hence, this study investigates the feasibility of helical tomotherapy (HT) as an alternative to BT. METHODS: Medical records of patients who underwent CCRT between 2000 and 2017 at a single institution were retrospectively reviewed. Patients with stage IIB-IVA cancers were selected based on the 2009 criteria of The International Federation of Gynaecology and Obstetrics. External beam radiation combined with chemotherapy was followed by either BT or HT. The propensity score matching of both groups was calculated using logistic regression analysis. Disease outcomes and treatment-related adverse events were compared between the 2 groups. RESULTS: The matched population included 70 BT patients and 35 HT patients. The 5-year progression-free survival rates for BT and HT were 72.6% and 72.5%, respectively (p=0.721). There was no difference in the overall survival rate between the two groups (p=0.203). The presence of acute and chronic gastrointestinal complications was also similar between the groups (p=0.460 and p=0.563, respectively). The chronic genitourinary toxicities were also comparable (p=0.105). CONCLUSIONS: HT boost treatment showed comparable disease outcomes with those observed with conventional BT in patients with advanced cervical cancer. HT could be a complementary boost protocol as a single modality or hybrid with BT in selected patients. Further studies with longer follow-up periods are warranted to confirm long-term outcomes.

Learning curve for sentinel lymph node mapping in gynecologic malignancies.

BACKGROUND AND OBJECTIVES: Only a few studies have reported the learning curve for sentinel lymph node (SLN) detection in gynecologic malignancies. We investigated the learning curve for SLN detection during robot-assisted laparoscopic surgery for endometrial and cervical carcinomas. METHODS: This retrospective analysis included patients with stage IA to IIA1 cervical cancer or stage I to III endometrial cancer who underwent SLN mapping using indocyanine green during robot-assisted laparoscopic surgery performed by a single surgeon. Learning curves were analyzed in consecutive cases using SLN detection rates and the cumulative sum (CUSUM) method. RESULTS: SLN mapping was achieved in 81.25% (65/80), 77.50% (62/80), and 66.25% (53/80) of the cases involving the right, left, and simultaneous bilateral pelvic areas, respectively. Learning curve analysis based on the cumulative detection rate showed initial fluctuations followed by stabilization; the time required for proficiency was discordant among the LN regions. However, the CUSUM method showed proficient mapping of the right, left, and bilateral SLNs after 27 to 28 cases. CONCLUSION: At least 27 cases were required for SLN mapping proficiency in gynecologic cancer; the learning period could influence the surgical quality. Further studies are warranted to confirm the impact of this learning curve on disease outcomes.

The impact of previous cesarean section (C/S) on the risk for post-molar gestational trophoblastic neoplasia (GTN).

OBJECTIVE: To investigate the relationship between previous cesarean section (C/S) and risk for post-molar gestational trophoblastic neoplasia (GTN). METHODS: Data from patients who were treated for hydatidiform moles between 1995 and 2016 were retrospectively reviewed. Patient age, gravidity, parity, abortion history, gestational age, pretreatment beta-human chorionic gonadotropin (HCG), previous molar pregnancy, clinical symptoms, enlarged uterus, theca lutein cyst, type of GTN, World Health Organization risk score, chemotherapy, and mode of delivery were recorded. Hazard ratios (HR) and 95% confidence intervals (CI) for variables associated with the occurrence of post-molar GTN and invasive mole were estimated by univariate and multivariate Cox proportional hazards models. RESULTS: From 1995 to 2016, 182 patients were diagnosed with molar pregnancy and underwent treatment. Patients with previous C/S (C/S group) had higher age (37.0 vs 32.8. p = 0.004), gravidity (3.1 vs 2.0, p < 0.001), and parity (1.6 vs 0.9, p < 0.001) than patients without previous C/S (non-C/S group). Post-molar GTN (43.5 vs 26.5%, p < 0.001), invasive mole (21.7 vs 3.7%, p < 0.001), hysterectomy (28.3 vs 6.6%, p < 0.001), and chemotherapy (45.7 vs 28.7%, p = 0.03) were more frequent in the C/S group. In multivariate analysis, independent risk factors for post-molar GTN were previous C/S (HR 5.1, 95% CI 2.1-12.7), abortion history (HR 6.3, 95% CI 2.5-15.6), and pretreatment ß-hCG (HR 1.3, 95% CI 1.1-1.6). CONCLUSIONS: In this study, C/S was a strong risk factor for occurrence of post-molar GTN and invasive mole. Aggressive treatment, such as multi-agent chemotherapy or hysterectomy, can be considered for hydatidiform moles in patients with a C/S history.

Doctor and patient awareness of treatment options for cervical intraepithelial neoplasia 1 (CIN 1): a survey questionnaire approach.

The purpose of this study was to investigate doctors' and patients' perceptions of cervical intraepithelial neoplasia 1 (CIN 1) and its treatment methods. A survey questionnaire was offered to obstetrics and gynaecology doctors and patients with CIN 1 in 2017. Only 43% of patients knew of this disease. Regarding perceptions of its aetiology, 64% of the patients perceived human papillomavirus infection to be the main cause of CIN 1. Patients' most preferred treatments were medication (20%), followed by alternative treatment (14%). Among doctors, regular follow-up was the most preferred method for managing CIN 1. The survey showed that current treatment modalities for CIN 1 were satisfactory to only half of doctors (50%) and patients (53%). Overall, 70% of doctors responded that new drug development for CIN 1 is needed. Although, CIN 1 is a low-grade lesion, doctors and patients expressed the desire for new therapeutic agents to manage it.IMPACT STATEMENTWhat is already known on this subject? In general, treatment is not recommended for CIN 1 because lesions are considered indicative of transient HPV infection and spontaneously regress in most patients.What do the results of this study add? Regular follow-up for CIN 1 were satisfactory to only half of doctors and patients. Thirty-six percent of patients wanted active treatment instead of regular follow-up. In addition, 70% of doctors responded that new drug development for CIN 1 is needed.What are the implications of these findings for clinical practice and/or further research? Our results support the need for therapeutic agents for CIN 1.

Overexpression of HER2/HER3 and clinical feature of ovarian cancer.

OBJECTIVES: Human epidermal growth factor receptor-2 (HER2) and 3 (HER3) belong to the epidermal growth factor receptor (EGFR) family of transmembrane receptor tyrosine kinases. In this study, we assessed HER2/HER3 expression levels in specimens of epithelial ovarian cancer and determined their correlation with clinical features of ovarian cancer. METHODS: Tissue microarrays (TMAs) were prepared from paraffin blocks of 105 ovarian tumour samples. HER2, HER3, PI3K, Akt, p-Akt, mTOR, p-mTOR, S6, and p-S6 expression levels were investigated using immunohistochemistry (IHC). HER2 and HER3 amplifications were determined using in situ hybridization (ISH). The correlation between HER2/3 expression and disease outcome of the patients including surgical outcome, progression-free survival (PFS) and overall survival (OS) was analysed. RESULTS: HER2 positivity was 3.8% by IHC and 5.7% by ISH, whereas that of HER3 was 12.4% and 8.6%, respectively. HER2 status by either IHC or ISH was not related to PFS (p=0.128, 0.168, respectively) and OS (p=0.245, 0.164, respectively). However, the HER3 status determined using fluorescence ISH was associated with poor PFS (p=0.035 on log rank test), which was a significant risk factor even after adjusting other possible risk factors in multivariate analysis (hazard ratio=2.377 [1.18-7.49], p=0.021). Expressions of Akt, p-mTOR, and S6 were also related with poor progression (p=0.008, 0.049, 0.014, respectively). CONCLUSION: HER3 is possibly an independent marker for poor prognosis in individuals with ovarian cancer, as the HER3 signalling pathway is distinct from that of HER2. The possibility of targeted therapy for patients with HER3 alteration in ovarian cancer should be evaluated.