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

Wichai Termrungruanglert,Nipon Khemapech,Tanitra Tantitamit,Piyalamporn Havanond 대한부인종양학회 2019 Journal of Gynecologic Oncology Vol.30 No.2

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, qualityadjusted 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.

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

Tantitamit, Tanitra,Termrungruanglert, Wichai,Oranratanaphan, Shina,Niruthisard, Somchai,Tanbirojn, Patuou,Havanond, Piyalamporn Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.16

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.

Incidence and Clinical Characteristic of Venous Thromboembolism in Gynecologic Oncology Patients attending King Chulalongkorn Memorial Hospital over a 10 Year Period

Oranratanaphan, S,Termrungruanglert, W,Khemapech, N Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

Background: Venous thromboembolisms (VTEs) constitute a group of diseases including deep vein thrombosis (DVT) and pulmonary embolism (PE). They regarded as the second leading cause of death in cancer patients and several studies have confirmed that VTEs have a negative impact on survival and recurrent rate in both ovarian and endometrial cancer cases. The incidence of VTEs differs worldwide and depends on several risk factors including race, underlying disease, lifestyle, body weight, BMI and genetic risk factors. There is heterogeneity of DVT rates between Asian and Western countries. This study was conducted in order to evaluate the character and incidence of VTEs in gynecologic oncology patients in King Chulalongkorn Memorial Hospital over a 10 year period. Materials and Methods: A retrospective chart review was performed with VTEs defined as objective diagnosis of acute DVT or PE with typical symptoms and signs. Diagnoses were approved byan internist and/or confirmed with imaging studies. Data from both outpatient and inpatient sessions of the affected cases from January 2004 to December 2013 were extracted. General characteristics of the patients were collected with details of the diseases, types of cancer, stage, date of diagnosis of cancer, operative data, treatment outcome, progression free survival and overall survival. Results: Thirty cases of VTEs were identified in a total 2,316 gynecologic oncology cases. The incidence of symptomatic VTEs in total gynecologic oncology patients in our institution is 1.295%. The incidence of VTEs in ovarian cancer patients in our institution was 5.9%. Duration for VTE detection ranged from 13 months before diagnosis of cancer to 33 months after diagnosis of cancer. Most of the VTE cases were detected in ovarian cancer patients (60%). The most common cell type was adenocarcinoma (moderately to poorly differentiated) which accounted for 26.7% of the cases. The second most common cell type was clear cell carcinoma with 23.3% of the cases. Thirty percent of VTE cases developed before cancer was diagnosed, 20% were diagnosed at the same time as cancer detection and fifty percent developed after cancer was diagnosed. Median disease free survival of the gynecologic oncology patients with VTE was 7.5 months. Median overall survival (OS) was 12 months. Median progession free survivals of DVT and PE groups were 11.5 and 5.5 months, respectively. OS of DVT and PE was 12.0 and 11.5 months respectively. Conclusions: The incidence of VTE in Asian countries is believed to be lower than in European or Western countries. From our retrospective review, the incidence of VTEs in all types of gynecologic oncology was 1.295%, much lower than reported in the West. The reason for the lower incidence may genetic differences. Another factor is that VTE in this review was symptomatic, which is less than asymptomatic VTE. More than half of VTEs in this study developed in ovarian cancer patients. The results are compatible with earlier reports that among gynecologic malignancies, the incidence of VTE is highest in ovarian cancer.

Acceptability of Self-Sampling HPV Testing Among Thai Women for Cervical Cancer Screening

Oranratanaphan, Shina,Termrungruanglert, Wichai,Khemapech, Nipon Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.17

Background: Acceptability of self-sampling HPV testing is confirmed worldwide. However, some cultural differences may affect this question. Therefore, this study was conducted to evaluate the acceptability of self-sampling HPV testing in Thai women. Materials and Methods: One hundred women aged 30-65 years with an intact cervix were included in this study. The participants were asked to do the Pap test by physicians and then brush type self-sampling instruments were assigned for self-collection and finally completed a questionnaire for acceptability evaluation. The questionnaire contains 2 parts. Part one covered general information of the participants and part two is the acceptability questions. Results: Mean age was 40.6 years. The incidence of high risk HPV detection in this study was 16%. The most common reason for doing Pap smear was for annual checkup. On the topic of ease of use, 85 % of the subjects agreed. Most of the participants (82%) reported that they felt less pain. However, reliability of the result was not satisfactory because 37% of the participants hesitated to rely on the results of the test. According to the price, if the price is less than 1,000 Baht (32.59 Baht = 1USD), 82% of the subjects would use it for their next screening. Conclusions: The acceptability of self-sampling device in this study is quite good but the reliability of the test was questioned by some of the participants. Moreover, the price of the test in Thailand may also influence the acceptability of the test.

Characteristics of Gynecologic Oncology Patients in King Chulalongkorn Memorial Hospital - Complications and Outcome of Pelvic Exenteration

Oranratanaphan, Shina,Termrungruanglert, Wichai,Sirisabya, Nakarin Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.4

Background: Pelvic exenteration is a procedure which includes enbloc resection of pelvic organs followed by surgical reconstruction. Aims include both cure and palliation but data for pelvic exenteration in Thailand are very limited. Objective: This study was conducted to evaluate characteristics of patients, operative procedure outcomes and complications. Materials and Methods: This retrospective review covered all of the charts of exenteration patients during January 2002 to December 2011. Baseline characteristic of the patients were collected as well as details of clinical results. Results: A total of 13 cases of pelvic exenteration were included. Most underwent total pelvic exenteration (9 cases) and the remainder posterior and anterior exenteration. Their primary cancers were ovarian, cervical and vulva. Mean operative time was 532 minutes (SD 160.2, range 270-750) and estimated blood loss was 2830 ml (1850, 1000-8000). Mean tumor size was 7.33 cm (3.75, 4-15). Mean hospital stay was 35.2 days (29.8, 13-109). The most common post operative complication was urinary tract infection. Overall disease free survival with a negative surgical margin was significantly better than in positive surgical margin patients (p=0.014). Conclusions: Surgical margin was the most significant prognostic factor for disease free survival, in line with earlier studies.

Salvage Chemotherapy in Recurrent Platinum-Resistant or Refractory Epithelial Ovarian Cancer with Carboplatin and Distearoylphosphatidylcholine Pegylated Liposomal Doxorubicin (Lipo-Dox^®)

Khemapech, Nipon,Oranratanaphan, S.,Termrungruanglert, W.,Lertkhachonsuk, R.,Vasurattana, A. Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.3

Background: To evaluate the efficacy and safety of distearoylphosphatidylcholine pegylated liposomal doxorubicin (DPLD) combined with carboplatin for the treatment of platinum resistant or refractory epithelial ovarian cancer (EOC) or fallopian tube cancer. Materials and Methods: A retrospective analysis of women who received DPLD with carboplatin for recurrent EOC or fallopian tube cancer in King Chulalongkorn Memorial Hospital Thailand from January 2006 to August 2011 was conducted. Patients were identified from the medical records and data on demographic factors, stage, histology, surgical findings, cytoreduction status, and prior chemotherapies were abstracted. The efficacy and toxicity of DPLD/carboplatin were evaluated. Progression-free (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Results: A total of 65 patients, 64 with platinum resistant or refractory epithelial ovarian cancer and 1 with fallopian tube cancer, were enrolled. DPLD and carboplatin were given for an average of 4.46 cycles per patient with a total of 273 cycles. Among the 65 evaluable patients, 0% achieved CR, 7.69% PR, 15.4% SD and 76.% PD. The overall response rate was 23.1%. With a median follow-up of 27.4 months, the median progression-free and median overall survival in the 36 patients was 4.46 months and 8.76 months respectively. In the aspect of side effects, palmar-plantar erythrodysesthesia (PPE) occurred in 33.3% (Grade I 22.2%, Grade II 11.1%) and mucositis in 41.7% (Grade I 27.8%, Grade II 13.9%) of all treatment cycles, all Grade 1 or 2. Anemia, leukopenia and thrombocytopenia occurred in 58.3% (Grade I 41.7%, Grade II 16.7%), 66.7% (Grade I 47.2%, Grade II 19.4%), and 22.2% (Grade I 16.6%, Grade II 5.56%) of cycle respectively, and were mostly Grade 1 or 2. Conclusions: DPLD, the second-generation PLD drug combined with carboplatin every 4 weeks, is effective and has low toxicity for treatment of patients with recurrent platinum-resistant or refractory epithelial ovarian cancer.

Feasibility and Safety of Robotic Surgery for Gynecologic Cancers

Manchana, Tarinee,Sirisabya, Nakarin,Vasuratna, Apichai,Termrungruanglert, Wichai,Tresukosol, Damrong,Wisawasukmongchol, Wirach Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.13

Background: To determine surgical outcomes, perioperative complications, and patient outcomes in gynecologic cancer patients undergoing robotic surgery. Materials and Methods: Surgical outcomes, including docking time, total operative time, console time, estimated blood loss (EBL), conversion rate and perioperative complications were retrospectively reviewed in 30 gynecologic cancer patients undergoing robotic surgery. Patient outcomes included recovery time and patient satisfaction, as scored by a visual analogue scale (VAS) from 0-10. Results: The operations included 24 hysterectomies with pelvic lymphadenectomy (PLD) and/or para-aortic lymphadenectomy, four radical hysterectomies with PLD, and two radical trachelectomies with PLD. Mean docking time was $12.8{\pm}9.7min$, total operative time was $345.5{\pm}85.0min$, and console time was $281.9{\pm}78.6min$. These times were decreased in the second half of the cases. There was no conversion rate. Three intraoperative complications, including one external iliac artery injury, one bladder injury, and one massive bleeding requiring blood transfusion were reported. Postoperative complications occurred in eight patients, most were minor. Only one patient had port herniation that required reoperation. Mean hospital stay was $3.5{\pm}1.7days$, and recovery time was $14.2{\pm}8.1days$. Two-thirds of patients felt very satisfied and one-third felt satisfied; the mean satisfaction score was 9.4 +0.9. Two patients with stage III endometrial cancer developed isolated port site metastasis at five and 13 months postoperatively. Conclusions: Robotic surgery for gynecologic cancer appears to be feasible, with acceptable perioperative complication rate, fast recovery time and high patient satisfaction.

Comparison of Perioperative and Oncologic Outcomes with Laparotomy, and Laparoscopic or Robotic Surgery for Women with Endometrial Cancer

Manchana, Tarinee,Puangsricharoen, Pimpitcha,Sirisabya, Nakarin,Worasethsin, Pongkasem,Vasuratna, Apichai,Termrungruanglert, Wichai,Tresukosol, Damrong Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.13

Purpose: To compare perioperative outcomes and oncologic outcomes in endometrial cancer patients treated with laparotomy, and laparoscopic or robotic surgery. Materials and Methods: Endometrial cancer patients who underwent primary surgery from January 2011 to December 2014 were retrospectively reviewed. Perioperative outcomes, including estimated blood loss (EBL), operation time, number of lymph nodes retrieved, and intra and postoperative complications, were reviewed. Recovery time, disease free survival (DFS) and overall survival (OS) were compared. Results: Of the total of 218 patients, 143 underwent laparotomy, 47 laparoscopy, and 28 robotic surgery. The laparotomy group had the highest EBL (300, 200, 200 ml, p<0.05) while the robotic group had the longest operative time (302 min) as compared with laparoscopy (180 min) and laparotomy (125 min) (p<0.05). Intra and postoperative complications were not different with any of the surgical approaches. No significant difference in number of lymph nodes retrieved was identified. The longest hospital stay was reported in the laparotomy group (four days) but there was no difference between the laparoscopy (three days) and robotic (three days) groups. Recovery was significantly faster in robotic group than laparotomy group (14 and 28 days, p =0.003). No significant difference in DFS and OS at 21 months of median follow up time was observed among the three groups. Conclusions: Minimally invasive surgery has more favorable outcomes, including lower blood loss, shorter hospital stay, and faster recovery time than laparotomy. It also has equivalent perioperative complications and short term oncologic outcomes. MIS is feasible as an alternative option to surgery of endometrial cancer.

National screening programs for cervical cancer in Asian countries

Eiko Saitoh Aoki,Rutie Yin,Kemin Li,Neerja Bhatla,Seema Singhal,Dwiana Ocviyanti,Kumiko Saika,서민아,김미선,Wichai Termrungruanglert 대한부인종양학회 2020 Journal of Gynecologic Oncology Vol.31 No.3

Cervical cancer is still one of the most common female cancers in Asia and the leading cause of cancer-related deaths in low- and middle-income countries. Nowadays, national screening programs for cervical cancer are widely provided in Asian countries. We reviewed the National Cancer Screening Program (NCSP) in China, India, Indonesia, Japan, Korea, and Thailand. The NCSP were established at varying times, from 1962 in Japan to 2014 in Indonesia. The primary screening method is based on cytology in all countries except for India and Indonesia. In India and Indonesia, visual inspection of the cervix with acetic acid (VIA) is mainly used as a primary screening method, and a “see and treat” strategy is applied to women with a positive VIA result. The starting age of NCSP ranges from 18 years in China to 30 years in Thailand. The screening interval is 2 years in all countries except for China and Indonesia, in which it is 3 years. Uptake rates of NCSP vary from 5.0%–59.7%. Many women in low- and middle-income countries still do not participate in NCSP. To improve uptake rates and thereby prevent more cases of cervical cancer, Asian countries should continue to promote NCSP to the public using various approaches.