A machine learning-based prediction model of pelvic lymph node metastasis in women with early-stage cervical cancer.

OBJECTIVE: To develop a novel machine learning-based preoperative prediction model for pelvic lymph node metastasis (PLNM) in early-stage cervical cancer by combining the clinical findings and preoperative computerized tomography (CT) of the whole abdomen and pelvis. METHODS: Patients diagnosed with International Federation of Gynecology and Obstetrics stage IA2-IIA1 squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma of the cervix who had primary radical surgery with bilateral pelvic lymphadenectomy from January 1, 2003 to December 31, 2020, were included. Seven supervised machine learning algorithms, including logistic regression, random forest, support vector machine, adaptive boosting, gradient boosting, extreme gradient boosting, and category boosting, were used to evaluate the risk of PLNM. RESULTS: PLNM was found in 199 (23.9%) of 832 patients included. Younger age, larger tumor size, higher stage, no prior conization, tumor appearance, adenosquamous histology, and vaginal metastasis as well as the CT findings of larger tumor size, parametrial metastasis, pelvic lymph node enlargement, and vaginal metastasis, were significantly associated with PLNM. The models' predictive performance, including accuracy (89.1%-90.6%), area under the receiver operating characteristics curve (86.9%-91.0%), sensitivity (77.4%-82.4%), specificity (92.1%-94.3%), positive predictive value (77.0%-81.7%), and negative predictive value (93.0%-94.4%), appeared satisfactory and comparable among all the algorithms. After optimizing the model's decision threshold to enhance the sensitivity to at least 95%, the 'highly sensitive' model was obtained with a 2.5%-4.4% false-negative rate of PLNM prediction. CONCLUSION: We developed prediction models for PLNM in early-stage cervical cancer with promising prediction performance in our setting. Further external validation in other populations is needed with potential clinical applications.

Adjuvant pelvic radiation versus observation in intermediate-risk early-stage cervical cancer patients following primary radical surgery: a propensity score-adjusted analysis.

OBJECTIVE: To compare survival outcomes, posttreatment complications, and quality of life (QoL) of early-stage cervical cancer patients with intermediate-risk factors between those who received adjuvant pelvic radiation and those without adjuvant treatment. METHODS: Stages IB-IIA cervical cancer patients classified as having intermediate-risk following primary radical surgery were included. After propensity score weighted adjustment, all baseline demographic and pathological characteristics of 108 women who received adjuvant radiation and 111 women who had no adjuvant treatment were compared. The primary outcomes were progression-free survival (PFS) and overall survival (OS). The secondary outcomes included treatment-related complications and QoL. RESULTS: Median follow-up time was 76.1 months in the adjuvant radiation group and 95.4 months in the observation group. The 5-year PFS (91.6% in the adjuvant radiation group and 88.4% in the observation group, p=0.42) and OS (90.1% in the adjuvant radiation group and 93.5% in the observation group, p=0.36) were not significantly different between the groups. There was no significant association between adjuvant treatment and overall recurrence/death in the Cox proportional hazard model. However, a substantial reduction in pelvic recurrence was observed in participants with adjuvant radiation (hazard ratio=0.15; 95% confidence interval=0.03-0.71). Grade 3/4 treatment-related morbidities and QoL scores were not significantly different between the groups. CONCLUSION: Adjuvant radiation was associated with a lower risk of pelvic recurrence. However, its significant benefit in reducing overall recurrence and improving survival in early-stage cervical cancer patients with intermediate-risk factors could not be demonstrated.

Prognostic Factors for Advanced Epithelial Ovarian Cancer Following Primary Cytoreductive Surgery or Neoadjuvant Chemotherapy.

AIM: To examine the association between clinicopathological factors and survival in advanced epithelial ovarian, tubal, and primary peritoneal cancers patients who had primary cytoreductive surgery (CRS) and those that received neoadjuvant chemotherapy (NAC). METHODS: Women who had CRS or NAC between 2008-2017 were included. Association between clinical characteristics, pretreatment imaging, serum markers, surgical and pathological factors, and disease recurrence/progression/death was examined in multivariable analysis. RESULTS: Two hundred and three women were recruited in this study (CRS 128 women and NAC 75 women). Median overall survival was 33.7 months for the CRS group and 27.9 months for the NAC group (p=0.04). Median progression-free survival was 14.9 months in the CRS group and 12.1 months in the NAC group (p=0.04). For the CRS group, factors independently associated with increased risk of death included primary peritoneal carcinoma (adjusted hazard ratio [aHR] 6.94), stable disease/progression at treatment completion (aHR 5.97), and initial tumor size of more than 12 cm (aHR 1.87). For the NAC group, stable disease/progression after complete treatment (aHR 6.45) and pre-treatment platelet to lymphocyte ratio of more than 310 (aHR 2.20) were significantly associated with an increased risk of death. CONCLUSIONS: NAC appeared to be a good alternative treatment for stage III/IV tubo-ovarian carcinoma. The worse survival outcome associated with primary peritoneal carcinoma and large initial tumor size in the patients who received CRS suggested that NAC could be an attractive option for those with these characteristics.

Change of contraceptive preference after the free-LARC program for Thai teenagers.

BACKGROUND: In 2014, the Thai government launched a free-of-charge long-acting reversible contraception (LARC) program for Thai female adolescents. However, its acceptance had not been reported. Therefore, this study aimed to describe contraceptive use among women of reproductive age before and after the program was implemented. METHODS: This retrospective cross-sectional study was carried out from the medical records of 9000 women of reproductive age, who attended the Family Planning Clinic at Maharaj Nakorn Chiang Mai Hospital between 2009 and 2018. The Chi-square test was used to compare the contraceptive methods administered before and after the program was implemented, and binary logistic regression was used to find the factors associated with implant use after completion of the program. RESULTS: Depot medroxy progesterone acetate (DMPA) injection was the most popular contraceptive method used among 40.9% of the women. The rates of subdermal implant use were increased significantly after the program was implemented (2.3-9.3%, p < 0.001). Implant use for adolescents aged less than 20 years increased from 2.6% to 56.4%, while DMPA was the most popular method used among adult women at 36.4%. Factors associated significantly with implant use after implement of the program included age of less than 20 years (aOR = 4.17 (CI: 1.84-9.44); p = 0.001) and nulliparity (aOR = 8.55 (CI: 3.77-19.39); p < 0.001). CONCLUSION: This study showed a significant increase in contraceptive implant use after the free-LARC program for adolescents had been applied. STATEMENT OF IMPLICATIONS: Contraceptive implant is the most effective hormonal reversible contraception. Its use rate is low among all age groups, but increased clearly after the free-of-charge program was applied for adolescents.

Awareness, perception and perpetration of cyberbullying by high school students and undergraduates in Thailand.

The modern online society requires everyone, especially children and young people, to learn how to use the Internet. Cyberbullying is one misuse that can be detrimental to the cyberbullied individuals' mental health and lifestyle, and it often ends up with the victim becoming depressed, fearful of society, and in the worst cases, suicidal ideation. The aim of this study is to investigate the awareness, perception, and perpetration of cyberbullying by high school students and undergraduates to find ways to prevent cyberbullying in the future. For this cross-sectional study, data were collected in 2020 from 14 schools throughout Thailand and 4 universities in Chiang Mai, Thailand, using two-stage sampling. Chi-squared tests were used to compare differences between the groups. Of the 2,683 high school students, girls perceived cyberbullying more than boys (81.6% vs. 75.4%; p <0.001), with those from the later academic years being more aware of cyberbullying (p = 0.033) and more likely to conduct cyberbullying behavior (p = 0.027). Of the 721 undergraduates, women were more aware of cyberbullying than men (92.1% vs. 82.7%; p <0.001). The most common cause of cyberbullying was aiming to tease the target (67.6% of high school students vs. 82.5% of undergraduates). The most commonly cyberbullying victimization was sending mocking or rebuking messages (29.6% of high school students and 39.6% of undergraduates). The most popular solutions for cyberbullying were to avoid leaving a trace on social media and be with friends who accept who you are. Our findings show that most of the cyberbullying perpetrators did not consider that their actions would have serious consequences and only carried out cyberbullying because of wanting to tease their victims. This is useful information for the cyberbullying solution center, teachers, and parents to recognize how to make the students realize the effects of cyberbullying on the victims.

Effectiveness of enhanced recovery after surgery protocol in open gynecologic oncology surgery: A randomized controlled trial.

OBJECTIVE: To examine the effectiveness of applying the recommended enhanced recovery after surgery (ERAS) protocol compared with our usual care in women with gynecologic malignancy undergoing elective laparotomy. METHODS: From June 2020 to May 2021, 93 women with gynecologic cancers (cervix, endometrium, and ovary) undergoing elective laparotomy at our institution were randomly assigned into an intervention group (ERAS protocol, 46 women) or control group (usual care, 47 women). For the intervention group, each woman was brought through the pre-specified ERAS protocol starting from preoperative counseling to postoperative management. For the control group, participants underwent routine standard care. The primary outcomes were length of hospital stay and postoperative pain. RESULTS: The intervention group demonstrated shorter hospital stay by 20 h (47.48 h vs 67.17 h, P = 0.02) with lower postoperative pain score at postoperative day 0 (1.58 vs 4.00, P < 0.01) and day 1 (1.00 vs 2.67, P < 0.01) while having decreased opioid consumption (P < 0.01). The intervention group also had faster recovery of gastrointestinal function. Overall, good compliance to most of the ERAS pathway domains was obtained. CONCLUSION: The ERAS protocol demonstrates benefits on shortening hospital stay, reducing pain, and bowel function recovery without increasing complications in our population. CLINICAL TRIAL REGISTRATION: The present study was registered at clinicaltrials.gov (NCT04201626) on December 3, 2019. Initial participant enrollment began on June 1, 2020. Access through URL of the registration site: https://clinicaltrials.gov/ct2/show/NCT04201626?cond=ERAS&cntry=TH&draw=2&rank=3.

Hormone Concentrations in Transgender Women Who Self-Prescribe Gender Affirming Hormone Therapy: A Retrospective Study.

BACKGROUND: Self-prescribed gender-affirming hormone therapy (GAHT) is common practice among transgender women, especially in resource-limited countries, yet the effectiveness of each GAHT regimen to achieve female range sex hormone concentrations is not known. AIM: To describe the use and sex hormone concentrations of various GAHT regimens among transgender women who self prescribe in Thailand. METHODS: This was a retrospective study in a community-based setting. Five hundred and 27 records of transgender women taking GAHT who were receiving care at a community health center between January 1, 2018, and December 31, 2020 were included for the analysis. MAIN OUTCOME MEASURES: Blood total testosterone and estradiol concentration after at least a 6-month period of GAHT. RESULTS: Multiple GAHT regimens were identified including oral estradiol valerate (EV), transdermal 17ß-estradiol gel, injectable EV with hydroxyprogesterone caproate, injectable estradiol benzoate with progesterone, oral EV with cyproterone acetate (CPA), and oral contraceptive pills (OCPs). The most common GAHT regimen used by 49.1% of the participants was OCPs that contained 0.035 mg of ethinyl estradiol and 2 mg of CPA. Only 25.2% of this group had female range testosterone concentrations (<50 ng/dL). Oral EV and CPA were used by 23.1% of the participants. Most of them used 12.5 mg of CPA and 47.7% of this group had female range testosterone concentrations. There was no statistical significance between mean testosterone concentrations in CPA 12.5 and 25 mg groups, (P = .086). CLINICAL IMPLICATIONS: The inadequate sex hormone levels found in these commonly self-prescribed GAHT regimens provide information regarding the efficacy and safety of GAHT regimens for health care providers working with transgender women in a community-based setting. STRENGTHS AND LIMITATIONS: This study reflected a real-world situation and provided hormonal profiles among transgender women taking self-prescribed GAHT. However, issues in recall, medical literacy, and adherence to the medication may limit the results. CONCLUSION: Combined hormonal contraceptive pill was a commonly used GAHT regimen in Thai transgender women who self prescribe GAHT. However, this regimen was not effective to decrease testosterone concentrations to the recommended range of less than 50 ng/dL. Overall, self-prescription of GAHT does not appear to be effective in reaching target sex hormone concentrations. Including health care providers in the prescription and monitoring of GAHT may be a more effective approach in the delivery of GAHT. Salakphet T, Mattawanon N, Manojai N, et al. Hormone Concentrations in Transgender Women Who Self-Prescribe Gender Affirming Hormone Therapy: A Retrospective Study. J Sex Med 2022;19:864-871.

Efficacy of Listening to Music on Pain Reduction during Colposcopy-Directed Cervical Biopsy: A Randomized, Controlled Trial.

Background and Objective: To investigate the efficacy of listening to music on pain reduction during colposcopy-directed cervical biopsy (CDB). Materials and Methods: From June 2020 to November 2021, 240 women undergoing CDB were enrolled. The participants were randomized into three groups: Group 1, colposcopic examination while wearing headphones and listening to music; Group 2, colposcopy while wearing headphones but not listening to music; Group 3 (control group), colposcopy while neither listening to music nor wearing headphones. All participating women completed a 10 cm visual analog scale for subjective pain at three time points: baseline, immediately after cervical biopsy, and 15 min after the procedure. The primary endpoint was the biopsy pain score. Result: Of the 240 women, a sample size of 80 was randomly assigned per group. The clinical-pathological and procedure-related characteristics of the participants in all groups were similar. The mean baseline pain score between each group was not significantly different (2.83 in the music group, 2.54 in group 2, and 2.94 in the control group, p = 0.47). There were no significant differences between each group in terms of mean biopsy pain score (4.21 in the music group, 4.24 in group 2, and 4.30 in the control group, p = 0.98). The differences in changes between the baseline pain score and the biopsy pain score were not statistically significant (1.39 in the music group, 1.70 in group 2, and 1.36 in the control group, p = 0.69). In the multiple comparison analysis, the differences in changes between the biopsy pain score and the baseline pain score between each group were also not statistically significant. There were no complications with the intervention observed. Conclusion: This study demonstrated that there was no beneficial effect of listening to music on pain reduction during colposcopy-directed cervical biopsies.

Health-related quality of life for early-stage cervical cancer survivors after primary radical surgery followed by radiotherapy versus radical surgery alone.

This study compared the quality of life (QoL) of 265 stage IA2-IIA cervical cancer patients treated with radical surgery alone (group 1: 137 patients) versus those who underwent primary radical surgery followed by radiotherapy (group 2: 128 patients) and identified clinical characteristics that predict the poor quality of life. All participants completed quality of life questionnaires: EORTC QLQ-C30 and CMU cervical cancer QoL. For the EORTC QLQ-C30, the study groups were comparable regarding global health status/QoL scale and summary scores. Group 1 participants had better scores on the physical functioning domain and some symptom scales/items. For the CMU Cervical Cancer QoL, group 1 participants had better scores on gastrointestinal, lymphatic, and sexual/hormonal domains. In multivariable analysis, adjuvant radiation was consistently associated with poor quality of life in most domains. In general, early-stage cervical cancer survivors had a satisfactory quality of life. The clinical significance of the quality of life score differences between the study groups remains debateable.Impact statementWhat is already known on this subject? For women with early cervical cancer, surgery is the main treatment providing not only a good chance for a cure by total removal of the cancer but also an opportunity to preserve the hormone-producing function of the ovary as well as the flexibility of the vagina. However, radiation treatment may be indicated after surgery in some patients depending on the findings from surgery. Because of the concern about increased complications and decreased long-term quality of life following the combined treatments, some may elect to avoid surgery and receive radiation alone in the first place. In this study, we compared the quality of life of women who had surgery alone to those who had surgery followed by radiation. This information is currently lacking in the medical literature.What do the results of this study add? We found that, in general, women with early cervical cancer had a satisfactory quality of life. For a patient who is surgically fit and chooses to receive primary surgery, if radiation is subsequently required, she could still expect the acceptable long-term quality of life-although slightly less satisfactory than receiving surgery alone but not inferior to those who receive primary radiation treatment.What are the implications of these findings for clinical practice and/or further research? These findings will be useful for pre-treatment counselling and posttreatment supportive care. The information regarding disease-related and treatment-induced morbidity should be thoroughly discussed with the patients before and after treatment. Also, the use of questionnaires examining general well-being together with a cancer-specific quality of life is recommended for the systematic evaluation of cancer survivors.

Effect of cancer stage on health-related quality of life of patients with epithelial ovarian cancer.

We compared the quality of life (QoL) of women with early versus advanced epithelial ovarian cancer and examined predicting factors for the poor QoL. We classified 157 participants into 108 with early disease (stage I-II) and 49 with advanced disease (stage III-IV). They completed two questionnaires: EORTC QLQ-C30 and Chiang Mai University (CMU) ovarian cancer QoL. For EORTC QLQ-C30, the study groups were comparable regarding global health status/QoL, functional scales, and summary scores. The advanced group had worse scores on symptom scales specifically appetite loss and constipation. For CMU Ovarian Cancer QoL, the advanced group had worse scores only in the gastrointestinal domain but not in urinary, lymphatic, and sexual/hormonal domains. These findings remained mostly unchanged after excluding those with recurrence. In multivariable analysis, currently receiving treatment was consistently associated with worse QoL scores. The advanced stage had more adverse impact only on the gastrointestinal domains of QoL, mainly during periods of receiving chemotherapy.IMPACT STATEMENTWhat is already known on this subject? Survival outcome for women with epithelial ovarian cancer varies depending mainly on stage. Those who survive advanced stage disease could expect long-term disease and treatment-related morbidities that significantly affected QoL. However, there has been very limited information regarding QoL of women who have the early disease in comparison to those with more advanced disease especially in the context of Asian culture.What do the results of this study add? Apart from the higher prevalence of gastrointestinal symptoms reported by the patients with advanced disease, the general well-being and other symptom-specific domains of QoL were comparable between women with early and advanced diseases. Receiving treatment is a consistent predictor for poor QoL.What are the implications of these findings for clinical practice and/or further research? In comparison to early-stage epithelial ovarian cancer, the advanced stage had more adverse impact only on the gastrointestinal domains of QoL, mainly during periods of receiving chemotherapy. This information will be useful for patient counselling. Future research should examine the underlying causes of this finding.

HIV-Infected Women with Low-Grade Squamous Intraepithelial Lesion on Cervical Cytology Have Higher Risk of Underlying High-Grade Cervical Intraepithelial Neoplasia.

OBJECTIVE: To evaluate the risk of histological high-grade cervical lesions defined as cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in women with human immunodeficiency virus (HIV) infection who had low-grade squamous intraepithelial lesions (LSIL) on cervical cytological screening compared with HIV-uninfected women who had similar cytology. METHODS: 127 HIV-positive women aged 18-65 years with LSIL cytology undergoing colposcopic examination between January 2008 and December 2019 at Chiang Mai University Hospital were reviewed. By matching 1:1 ratio for age (±5 years) and examination time period (±12 months), 127 HIV-negative women with LSIL cytology in the same period were recruited as controlled subjects for comparison. The patients' characteristics, HIV status, CD4 counts, antiretroviral therapy, and histopathology on cervical biopsy were analyzed. RESULTS: HIV-infected women significantly had early sexual debut (age < 20 years) and more sexual partners (≥2) than HIV-uninfected women. The risk of underlying CIN2+ in HIV-infected women was significantly higher than that in HIV-negative women (20.5% vs. 9.4%, p = 0.021) with an odds ratio (OR) of 2.47 and 95% confidence interval (CI) = 1.18-5.14. After adjustment, the risk of underlying CIN2+ in HIV-infected women remained significantly higher than that in HIV-uninfected women (adjusted OR = 2.55, 95% CI = 1.11-5.82, p = 0.027). CONCLUSION: Among women with LSIL on cervical cytology, the risk of underlying CIN2+ in HIV-infected women was approximately 2.5 times higher than those without HIV infection. Colposcopy is indicated particularly in the case of women with a long duration of HIV infection.

iPMI: Machine Learning-Aided Identification of Parametrial Invasion in Women with Early-Stage Cervical Cancer.

Radical hysterectomy is a recommended treatment for early-stage cervical cancer. However, the procedure is associated with significant morbidities resulting from the removal of the parametrium. Parametrial cancer invasion (PMI) is found in a minority of patients but the efficient system used to predict it is lacking. In this study, we develop a novel machine learning (ML)-based predictive model based on a random forest model (called iPMI) for the practical identification of PMI in women. Data of 1112 stage IA-IIA cervical cancer patients who underwent primary surgery were collected and considered as the training dataset, while data from an independent cohort of 116 consecutive patients were used as the independent test dataset. Based on these datasets, iPMI-Econ was then developed by using basic clinicopathological data available prior to surgery, while iPMI-Power was also introduced by adding pelvic node metastasis and uterine corpus invasion to the iPMI-Econ. Both 10-fold cross-validations and independent test results showed that iPMI-Power outperformed other well-known ML classifiers (e.g., logistic regression, decision tree, k-nearest neighbor, multi-layer perceptron, naive Bayes, support vector machine, and extreme gradient boosting). Upon comparison, it was found that iPMI-Power was effective and had a superior performance to other well-known ML classifiers in predicting PMI. It is anticipated that the proposed iPMI may serve as a cost-effective and rapid approach to guide important clinical decision-making.

Risk of High-Grade Cervical Lesions in Atypical Squamous Cells of Undetermined Significance (ASC-US) Cytology: Comparison between HIV-Infected and HIV-Negative Women.

BACKGROUND AND OBJECTIVE: Women with human immunodeficiency virus (HIV) infection have an increased risk of HPV infection, cervical neoplasia. This study was undertaken to compare the risk of having high-grade cervical lesions defined as cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in HIV-infected versus HIV-uninfected women who had atypical squamous cells of undetermined significance (ASC-US) on cervical cytology. METHODS: Fifty-seven HIV-positive women aged 25-65 years with ASC-US cytology undergoing colposcopic examination between January 2008 and December 2020 at Chiang Mai University Hospital were reviewed. By matching 1:5 ratio, 285 HIV-negative women with ASC-US cytology in the same period were recruited as controlled subjects for comparison. The patient characteristics, HIV status, CD4 cell count within 6 months of colposcopy, antiretroviral therapy, parity, contraception, smoking history, number of sexual partners, and histopathology on cervical biopsy were analyzed. RESULTS: Mean age ± SD of the HIV-positive and HIV-negative groups was 44.28 ± 8.53 years and 44.28 ± 9.68 years, respectively. HIV-positive women were significantly less likely to use contraceptive methods (36.8 % versus 48.8 % in HIV-negative women; P = 0.002). HIV-infected women significantly had more sexual partners than HIV-uninfected women. Both groups had similar risk for CIN 2+ (5.3 % in HIV-positive women compared with 4.9 % in HIV-negative women; odds ratio [OR] = 1.08, 95% confidence interval [CI] = 0.30 -3.87). After adjustment for no contraception use and number of sexual partners, the risk of CIN2+ in HIV-infected women remained unchanged; adjusted OR= 1.15, 95% CI = 0.27-4.92, P= 0.846). CONCLUSION: The risk of underlying high-grade cervical lesions in women with ASC-US on cervical cytology was approximately 5 %, regardless of HIV status.