Cost-Effectiveness of Primary HPV Screening Strategies and Triage With Cytology or Dual Stain for Cervical Cancer.

To identify the optimal cost-effective strategy for cervical cancer screening program in Thailand by comparing the different algorithms which based on the use of primary human papilloma virus (HPV) assay. We use a Microsoft Excel-based spreadsheet to calculate the accumulated cases of preinvasive and invasive cervical cancer and the budget impact of each screening program. The model was developed to determine the cost-effectiveness of 3 screening strategies: pooled HPV test with reflex liquid-based cytology triage, HPV genotyping with reflex p16/ki67 dual stain cytology, and pooled HPV test with dual stain. The main outcomes were the total cost, incremental quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). Strategy entailing primary HPV genotyping and reflex dual stain cytology is the least costly strategy (total cost US$37 893 407) and provides the similar QALY gained compared to pooled high-risk HPV testing with reflex dual stain (Average QALY 24.03). Pooled HPV test with reflex dual staining is more costly compared to strategy without reflex dual staining. The ICER was US$353.40 per QALY gained. One-way sensitivity analysis showed that the model is sensitive to the cost of dual stain and the cost of cancer treatment. Decreasing the incidence of cervical cancer case and increasing the QALYs can be successful by using dual stain cytology as the triage test for pooled HPV test or HPV genotyping. The result of our analysis favors the use of HPV genotyping with the reflex dual stain as it offers the most QALY at the lowest cost.

Application of Sentinel Lymph Node Technique to Transvaginal Natural Orifices Transluminal Endoscopic Surgery in Endometrial Cancer.

STUDY OBJECTIVE: This report outlines our first experience of sentinel lymph node (SLN) mapping in the natural orifices transluminal endoscopic surgery (NOTES) technique, which is the combination of the least invasive surgical approach and the least invasive way of assessing lymph node status. DESIGN: Descriptive study (Canadian Task Force classification III). SETTING: Tertiary referral and educational center. PATIENTS: Four patients with endometrial cancer clinical stage 1. INTERVENTIONS: NOTES with SLN mapping using an indocyanine green-based near-infrared fluorescence imaging technique. MEASUREMENTS AND MAIN RESULTS: The average operative time was 182.75 minutes (standard deviation, 34.5). Mean estimated blood loss was 67.5 mL (standard deviation, 39.4). All patients had surgical staging of International Federation of Gynecology and Obstetrics stage IA (pT1aN0). The overall detection rate and bilateral detection rate were 100% (4/4). All procedures were successfully completed without complication or conversion to conventional laparoscopy. CONCLUSION: In our preliminary experience, SLN mapping in NOTES surgery appears to be feasible and safe. It can be considered as an alternative method to reduce morbidity from radical lymphadenectomy and provide the benefits from the NOTES technique. However, studies in a larger population are necessary.

Pelvic Retroperitoneal Cellular Leiomyoma: A Case Report.

Leiomyomas are common benign gynecological tumors and usually arise in the uterus. The retroperitoneal cellular leiomyoma, one of the unusual manifestations, is a rare tumor. Diagnosis and treatment are challenges. We report a case of 65-year-old women presented with an asymptomatic mass beneath the right posterior vaginal mucosa. CT imaging revealed heterogeneous mass 6 cm in the pelvic cavity abutted lower segment of uterus, cervix, and vagina. The provisional diagnosis was subserosal cervical leiomyoma. She underwent exploratory laparotomy. Intra-operative, a normal size uterus was found separately from retroperitoneal pelvic mass at the level of internal os. Histological report confirmed cellular leiomyoma later Total hysterectomy, bilateral salpingoophorectomy and completely excision of tumor were achieved with good outcome. Our patient represents the rare case of retroperitoneal cellular leiomyoma, which is hardly identified from internal examination and preoperative imaging. Surgical removal is essential for pathological diagnosis and treatment.

Cost-effectiveness analysis of single-dose or 2-dose of bivalent, quadrivalent, or nonavalent HPV vaccine in a low/middle-income country setting.

OBJECTIVE: To compare the health impact and economic benefits among individuals who did not receive the human papillomavirus (HPV) vaccine to those who received a single dose, or 2 doses. The comparison was stratified by 4 types of vaccine in conjunction with primary HPV screening in a low/middle-income country setting. METHODS: A Markov model was employed to simulate HPV infection and cervical cancer in a cohort of 100,000 12-year-old girls free of HPV. The study scrutinized 9 strategies: 1 dose and 2 doses of 2vHPV (Cervarix®), 2vHPV (Cecolin®), 4vHPV (Gardasil®), 9vHPV vaccine (Gardasil9®), and no vaccination. The primary outcome measure was the quality-adjusted life year (QALY) of each strategy. Incremental cost-effectiveness ratios were estimated over a lifetime horizon, accompanied by sensitivity analyses conducted. RESULTS: All vaccination programs yielded 41,298-71,057 QALYs gained accompanied by cost savings of 14,914,186-19,821,655 USD compared to no vaccination. Administering 2 doses of 9vHPV vaccine emerged as the most cost-effective strategy, boasting 406 USD/QALY, within a lower willingness to pay threshold. Sensitivity analysis demonstrated an 80% probability of the cost-effectiveness of the 2 doses of 9vHPV vaccine regimen. Furthermore, uncertainty around the costs of vaccination and vaccine efficacy exerted the most substantial influence on the cost-effectiveness findings. CONCLUSION: Oping for 2 doses of 9vHPV vaccine in conjunction with a primary HPV screening represents the most cost-effective option for implementing a school-based HPV vaccination program targeting 12-year-old girls in Thailand. Such findings provide valuable insights for policymakers in the realm of cervical cancer prevention.

Outcomes and Prognostic Factors of Patients with Platinum- Resistant or Refractory Epithelial Ovarian Cancer, Fallopian Tube Cancer and Peritoneal Cancer.

OBJECTIVE: To determine the survival outcomes and prognostic factors of the patients with recurrent platinumresistant and refractory epithelial ovarian cancer (EOC), tubal, and peritoneal cancer. METHODS: Women with recurrent platinum-resistant and refractory EOC, tubal and peritoneal cancer who received treatment at the HRH Princess Maha Chakri Sirindhorn Medical Center (MSMC) between January 2010 and December 2019 were included. Demographic data, serum marker, surgical factors, pathological factors and response of treatment were reviewed. Kaplan-Meier was used to calculate survival outcome. RESULT: Forty patients were recruited in this study (platinum-resistant 24 patients and refractory 16 patients). The median survival times were 19 and 21 months in and platinum-resistant and platinumrefractory patients, respectively. There were no significant differences in overall survival according to age, comorbidity, tumor grading, primary treatment, and secondary surgery. However, histology of clear cell carcinoma may associate with increased risk of death. The median overall survival of patients with clear cell carcinoma, serous carcinoma, and others were 14.4, 22.9, and 32.2, respectively (p = 0.003). CONCLUSION: Almost 10 years, the survival rate of the patients in these group has not increased despite new treatments option. Novel strategies should be considered in National policy of the treatment for ovarian cancer in our country.

Prognostic Value of The Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Platelet Count for Platinum-Sensitive Recurrent Epithelial Ovarian Cancer.

OBJECTIVE: To study the prognostic value of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and platelet count in patients with platinum-sensitive recurrent epithelial ovarian cancer (PS-ROC). METHODS: This was a retrospective study on a database of platinum-sensitive recurrent epithelial ovarian cancer patients who received treatment at HRH Princess Maha Chakri Sirindhorn Medical Center (MSMC) between January 2010 and December 2020. The patients' demographic data, surgical factors, pathological factors, laboratory findings, and response to treatment were reviewed from the patients' medical records. Survival analysis was conducted using the Kaplan-Meier survival estimate and Cox regression model. RESULTS: In total, 56 patients were recruited in this study. The median overall survival (OS) and progression-free survival (PFS) were 33 (95%CI 23-43) and 11 (95%CI 8-16) months, respectively. Survival analysis showed a high PLR was associated with decreased OS compared with low value but no significant difference in PFS. High NLR was associated with poor OS and PFS. There was no association between the platelet count and survival outcome (OS and PFS). In the multivariable Cox regression analysis, the NLR, PLR, and platelet count were not significant prognostic factors for survival outcome. However, low hemoglobin and a decreased disease-free interval were significantly associated with poor PFS. A white blood cell count (WBC) ≥ 8,000 cells/mm3 was a poor prognostic factor for overall survival (Adjusted HR 7.64; 95%CI: 2.21-26.42; p-value = 0.001). CONCLUSIONS: The NLR, PLR, and platelet count were not associated with both the OS or PFS in patients with PS-ROC. However, the WBC level is an easy, readily available, and economical way to predict survival outcomes in PS-ROC patients and may help physicians to tailor therapeutic interventions in the future.

An Ultralate Female Growing Teratoma Syndrome: 19 Years after Aggressive Treatment for Advanced Ovarian Immature Teratoma.

We report a rare case with the late occurrence of growing teratoma syndrome (GTS). A 24-year-old woman with Grade 3 immature teratoma of ovary underwent complete surgery and chemotherapy. Nineteen years later, she developed hematuria and pelvic mass that was completely resected and pathology revealed mature cystic teratoma. She has regularly followed up with tumor marker and computed tomography every three months. No evidence of disease has been detected throughout 14 years. In addition, we present a brief review of literature of ovarian GTS in the last decade. We have found that advanced stage, high grade, or early recurrence of germ cell tumor (GCT) could be the risk factors of GTS. It tends to appear within 1 year if the patients had the incomplete resection of primary disease. We stress the importance of long-term follow-up after treatment GCT to early recognition and treatment.

Laparoscopic versus open radical hysterectomy in women with early stage cervical cancer: A systematic review and meta-analysis.

This review aimed to evaluate the short term and long-term outcomes of laparoscopic radical hysterectomy (LRH) versus abdominal radical hysterectomy (ARH) for early-stage cervical cancer. A search of PubMed, Medline and Scopus databased from 2000 to 2018 was conducted. Thirty studies were retrieved including 22 retrospective cohort studies and 8 prospective cohort studies. LRH was comparable with ARH in 5-year overall survival (RR = 1.0. 95%CI 0.98-1.03; p = 0.33) and 5-year disease-free survival (RR = 1.02 95%CI 0.97-1.06; p = 0.98). The majority of included studies reported the negative cancer factors which drive adjuvant therapy were similar between two approaches. LRH was associated with lower blood loss and blood transfusion, less postoperative complication, shorter hospital stays and similar intraoperative complication rate compared to ARH. Our data suggested LRH for early-stage cervical cancer was as safe and effective in terms of long-term outcomes, but with lower surgical morbidities.

Bladder Safety during Natural Orifice Transluminal Endoscopic Surgery Hysterectomy in the Patients with Extensive Vesicouterine Adhesion.

Adhesion at the vesicouterine fold presents a great challenge when performing hysterectomy through transvaginal natural orifice transluminal endoscopy surgery (NOTES) in women with a history of cesarean section. An attempt to lyse adhesions often prolongs the procedure and may inadvertently result in cystostomy. The purpose of this report is to demonstrate a safe technique for the lysis of vesicouterine adhesions during NOTES hysterectomy. We present the cases of two patients with a history of cesarean section. Severe adhesions at the vesicouterine peritoneum were encountered in both cases, and one patient had an extensive adhesion involving lower half of the uterus. Although the lateral approach is sufficient in most cases, it does not allow a surgeon to approach the peritoneal cavity if there is extensive adhesion. In cases such as these, direct dissection of the adhesion on the uterus is required.

Cost effectiveness analysis of HPV primary screening and dual stain cytology triage compared with cervical cytology.

OBJECTIVES: To assess the clinical and cost-effectiveness of human papillomavirus (HPV) primary screening triage with p16/Ki-67 dual stain cytology compared to cytology. METHODS: We conducted an Excel®-based budget impact model to estimate the preinvasive and invasive cervical cancer cases identified, mortality rate, direct medical costs, quality-adjusted life years (QALYs) and the incremental cost-effectiveness analysis of two strategies from the healthcare payer perspective. The study population is a cohort of women 30-65 years of age presenting for cervical screening. RESULTS: HPV primary screening triage with p16/Ki-67 dual stain showed higher sensitivity without losing specificity compared to conventional Pap smear. The improving the screening performance leads to decrease the prevalence of precancerous lesion, annual incidence and mortality of cervical cancer. The incidence of cervical cancer case detected by new algorithm compared with conventional method were 31,607 and 38,927, respectively. In addition, the new algorithm was more effective and more costly (average QALY 24.03, annual cost $13,262,693) than conventional cytology (average QALY 23.98, annual cost $7,713,251). The incremental cost-effective ratio (ICER) per QALY gained was $1,395. The sensitivity analysis showed if the cost of cytology and HPV test increased three times, the ICER would fall to $303/QALY gained and increased to $4,970/QALY gained, respectively. CONCLUSION: Our model results suggest that screening by use of HPV genotyping test as a primary screening test combined with dual stain cytology as the triage of HPV positive women in Thai population 30-65 years old is expected to be more cost-effective than conventional Pap cytology.

Is It the Time for Laparoscopic Management of Early-stage Ovarian Malignancies?

The laparoscopic management of early-stage ovarian cancer remains controversial. Some surgeons hesitate to perform laparoscopic staging due to concern with the adequacy of staging, the possibility of tumor spillage and risk of port-site metastasis. Previous studies and literature reviews have reinforced the argument and supported the use of laparoscopy. However, the results were drawn with limited sample size obtained from case-series and case-control studies which result in difficult to make definite conclusions. Till date, the list of laparoscopic procedures has grown at a pace consistent with improvements in technology and technical skill of the surgeon. The number of studies with larger sample size, more prospective data, and longer duration of follow-up has been increasing. This review serves as an update on safety, feasibility, surgical, and oncological outcomes in cases of early-stage ovarian cancer treated by laparoscopic surgery of the literature published since 2008. We aim to clarify whether laparoscopy is safe and effective enough to be considered as standard management. Rely on nonrandomize studies, the current clinical evidence supports the role of laparoscopy in the management of early-stage ovarian cancer. Laparoscopy appears to offer several perioperative benefits without compromise of surgical morbidity and oncological outcome.

Outcome and Management of Uterine Leiomyosarcoma Treated Following Surgery for Presumed Benign Disease: Review of Literature.

Uterine leiomyosarcoma (uLMS) is a rare and aggressive cancer, usually diagnosed incidentally at the time of myomectomy or hysterectomy. There have been concerns for several years about the fact that the inadvertent disruption of occult uLMS may have a negative impact on patient outcome. This study reviews the outcome and management of patients with a diagnosis of uLMS after surgery for presumed benign disease. We conducted a literature search in which 47 published English-language articles were obtained for evaluation. A total of 23 studies with outcomes data were included. It is evidenced that patients who underwent surgery with tumor disruption resulted in poorer outcomes compared with en bloc tumor, especially by power morcellation. The power morcellation was associated with an increased risk of recurrence, shorten time to recurrence, and upstage after re-exploration. Early re-exploration and surgical staging are appreciated for better prognosis and may alter postoperative treatment. We also updated on the incidence and preoperative evaluation to assess the risk of patient and give an effective counseling.

Clear cell adenocarcinoma of the cervix in second generation young women who are without maternal exposure to diethylstilbestrol: A case report.

Clear cell adenocarcinoma of the cervix (CCAC) is a rare type of gynecological cancer. The risk factors and pathogenesis have yet to be clearly determined. This is a case report of a 19-year-old woman, who was never exposed to DES from her mother, who had gone for an examination for vaginal bleeding. A polypoid mass measured at 3 cm presenting in her cervix was discovered. Histological diagnosis following cervical biopsy proved the tumor to be a clear cell carcinoma. The patient was then referred to our hospital. A loop electrosurgical excision procedure (LEEP) was done and the pathological diagnosis was confirmed for clear cell carcinoma with a positive endocervical margin. Radical hysterectomy, pelvic lymphadenectomy and incidental appendectomy were achieved without any complications. The microscopic findings had revealed no residual tumor. The patient did not require adjuvant treatment. No sign of recurrence has been detected throughout 6 months of follow-up. We have performed the literature review on the clinical presentation, pathogenesis, pathology, diagnosis, treatment, and prognosis of this unusual tumor.

A Model Approach for Assessing the Benefits of HPV Testing against Cytology in Screening for Cervical Cancer Precursors in Thailand

Objective: The aim of this study was to compare the efficacy of HPV 16/18 genotyping test, high risk HPV DNA testing, alone and in conjunction with the liquid-based cytology method in screening for cervical cancer precursors. Methods: A Markov model was used to describe the course of the cases of CIN2+ that had been detected over a 35 year period. Screening programs started at age 30 and were performed at an interval of once every five years. The model compared three strategies of HPV 16/18 genotyping with reflex cytology triage, high-risk HPV testing alone with referral to colposcopy and cytology-based screening with referral to colposcopy. We assumed the rate of patients lost to follow-up for those referred to colposcopy would be 0%. The clinical parameters were estimated using the data from a study conducted by the Thailand National Cancer Institute. Result: Of the three screening strategies evaluated, the high risk HPV DNA testing alone was the most effective for detecting CIN2+ over the 35 year study period. It detected 143 and 510 cases per 100,000 women more than the HPV 16/18 genotyping test and cytology-based strategy, respectively. The HPV genotyping test detected 368 cases per 100,000 women more than the cytology-based approach. In addition, when viewed with five year intervals, there were missed cases totaling approximately half of the detected cases screened by the cytology strategy and 10% of cases detected with screening by the HPV genotyping test. Conclusion: This study strongly indicates that HPV/DNA testing is preferable to cytology-based screening for cervical cancer precursors. However, the balance between the benefits, burdens and cost of each screening program should be considered.

Cost-effectiveness analysis study of HPV testing as a primary cervical cancer screening in Thailand.

OBJECTIVES: The aim of this study is to compare the cost and benefit of four different cervical cancer screening strategies involving primary HPV 16/18 genotyping, hrHPV testing alone and cytology for detecting CIN2 +. METHODS: Economical analysis using Markov modeling approach to combine the epidemiological data from current population-based study of The National Cancer Institute of Thailand. A cohort of 100,000 hypothetical female population age 30-65 years was simulated in each strategy. The compared strategies are HPV 16/18 genotyping with reflexed cytology, hrHPV testing alone followed by colposcopy, Papanicolaou standard cytology and liquid based cytology followed by colposcopy. The interval of screening was 5 years' interval. The main outcomes were defined as a number of CIN2 + cases and cost per 100,000 women screening over 35 years. RESULTS: Model predictions indicated that, the most cost-effectiveness strategy is hrHPV testing alone by reducing cost and also increase CIN2 + detection rate. It identify an additional 130 cases and decrease cost by 46,950,840 THB (1,394,441 USD) per 100,000 women screened when compared to HPV 16/18 genotyping. Compared with cytology, hrHPV testing decrease cost by 51,279,781 THB (1,523,011 USD) and detected more 506 cases of CIN2 +. From sensitivity analysis, the cost of HPV testing, cost of colposcopy, incidence of HPV infection and sensitivity of cytology may affect the results. (1 USD = 33.67 Baht). CONCLUSION: The results of this cost-effectiveness analysis support the full scale implementation of HPV testing as a primary cervical cancer screening in Thailand.

Cost-Effectiveness Analysis of Different Management Strategies for Detection CIN2+ of Women with Atypical Squamous Cells of Undetermined Significance (ASC-US) Pap Smear in Thailand.

BACKGROUND: To identify the optimal cost effective strategy for the management of women having ASC-US who attended at King Chulalongkorn Memorial Hospital (KMCH). DESIGN: An Economical Analysis based on a retrospective study. SUBJECT: The women who were referred to the gynecological department due to screening result of ASC-US at King Chulalongkorn Memorial Hospital, a general and tertiary referral center in Bangkok Thailand, from Jan 2008 - Dec 2012. MATERIALS AND METHODS: A decision tree-based was constructed to evaluate the cost effectiveness of three follow up strategies in the management of ASC-US results: repeat cytology, triage with HPV testing and immediate colposcopy. Each ASC-US woman made the decision of each strategy after receiving all details about this algorithm, advantages and disadvantages of each strategy from a doctor. The model compared the incremental costs per case of high-grade cervical intraepithelial neoplasia (CIN2+) detected as measured by incremental cost-effectiveness ratio (ICER). RESULTS: From the provider's perspective, immediate colposcopy is the least costly strategy and also the most effective option among the three follow up strategies. Compared with HPV triage, repeat cytology triage is less costly than HPV triage, whereas the latter provides a more effective option at an incremental cost-effectiveness ratio (ICER) of 56,048 Baht per additional case of CIN 2+ detected. From the patient's perspective, the least costly and least effective is repeat cytology triage. Repeat colposcopy has an incremental cost-effectiveness (ICER) of 2,500 Baht per additional case of CIN2+ detected when compared to colposcopy. From the sensitivity analysis, immediate colposcopy triage is no longer cost effective when the cost exceeds 2,250 Baht or the cost of cytology is less than 50 Baht (1USD = 31.58 THB). CONCLUSIONS: In women with ASC-US cytology, colposcopy is more cost-effective than repeat cytology or triage with HPV testing for both provider and patient perspectives.