Correction: Chua et al. Cost-Effectiveness Analysis of HPV Extended versus Partial Genotyping for Cervical Cancer Screening in Singapore. Cancers 2023, 15, 1812.

The authors wish to revise two words in Table 1 row 3, and the first paragraph of Section 2 [...].

Cost-Effectiveness Analysis of HPV Extended versus Partial Genotyping for Cervical Cancer Screening in Singapore.

Human papillomavirus (HPV) partial genotyping (PGT) identifies HPV16 and HPV18 individually, alongside 12 other high-risk HPV genotypes (hrHPV) collectively. HPV extended genotyping (XGT) identifies four additional hrHPV individually (HPV31, 45, 51, and 52), and reports the remaining eight in three groups (HPV33|58; 56|59|66; 35|39|68). Quality-adjusted life years (QALY), health care resource use, and costs of XGT were compared to PGT for cervical cancer screening in Singapore using DICE simulation. Women with one of the three hrHPV identified by XGT (HPV35|39|68; 56|59|66; 51), and atypical squamous cells of undetermined significance (ASCUS) on cytology, are recalled for a repeat screening in one year, instead of undergoing an immediate colposcopy with PGT. At the repeat screening, the colposcopy is performed only for persistent same-genotype infections in XGT, while with PGT, all the women with persistent HPV have a colposcopy. Screening 500,122 women, aged 30-69, with XGT, provided an incremental cost-effectiveness ratio (ICER) versus PGT of SGD 16,370/QALY, with 7130 (19.4%) fewer colposcopies, 6027 (7.0%) fewer cytology tests, 9787 (1.6%) fewer clinic consultations, yet 2446 (0.5%) more HPV tests. The XGT ICER remains well below SGD 100,000 in sensitivity analyses, (-SGD 17,736/QALY to SGD 50,474/QALY). XGT is cost-effective compared to PGT, utilizes fewer resources, and provides a risk-based approach as the primary cervical cancer screening method.

Health care provider's experience and perspective of cervical cancer screening in Singapore: A qualitative study.

Background: In Singapore, the current cervical cancer screening (CCS) coverage rate of 48% falls below the national target of 70%. Health care providers (HCPs) play a critical role in promoting CCS uptake. However, there is limited understanding of the perspectives of HCPs regarding CCS. Hence, we aimed to understand the challenges encountered by HCPs delivering CCS in different care settings in the Singapore health system. We also aimed to explore perspectives on newer features of CCS such as self-sampling and HPV genotyping. Methods: Physicians, nurses, program administrators and laboratory technicians involved with CCS were invited for a one-on-one semi-structured interview conducted over Zoom between May to August 2021. The interviews were transcribed and analyzed using thematic analysis. Results: Eighteen HCPs from 12 institutions were interviewed. Most participants were women (61.1%) and worked in public health institutions (72.2%). For factors influencing CCS, nine key themes were identified and organized into four categories: (1) patient factors, (2) HCP factors, (3) health system factors and (4) health promotion factors. Key themes commonly highlighted by study participants were related to patients' preferences and acceptance for screening, the processes of delivering CCS, the national priority for cervical cancer and the effectiveness of existing health promotion efforts. Five key themes were identified for CCS innovations. Self-sampling was viewed favorably to increase CCS uptake, while primary HPV screening with HPV partial genotyping had higher sensitivities to detect pre-cancers and cancers compared to cytology. Extended HPV genotyping beyond HPV16/18 could play an important role in CCS with increasing HPV vaccination coverage, as well as in the management of persistent HPV infection. Conclusion: In Singapore, HCPs face multiple challenges for CCS in practice. Insights from this study are directly relevant to, and useful for developing policies around national CCS programs and treatment guidelines.

Reaching the women with the greatest needs: Two models for initiation and scale-up of gynecologic oncology fellowship trainings in low-resource settings.

Women in low- and middle-income countries (LMICs) are significantly more likely to develop and die from invasive cervical cancer, while rates of other gynecologic malignancies are comparable to those faced by women in high-income countries. Despite this increased need, there are few specialist physicians in LMICs available to treat women with gynecologic cancers. Training specialists in low-resource settings faces multiple challenges, including ensuring protected time from other clinical demands, access to best practice guidelines, training that is tailored to the specific challenges faced in the trainee's environment, and isolation from other fully trained professionals and securing support services. In addition, training specialists from LMICs in high-resource settings is costly and return of trainees to their own country is not guaranteed. Here we describe two approaches to gynecologic oncology training in LMICs. The International Gynecologic Cancer Society (IGCS) developed the Global Curriculum Mentorship and Training Program (Global Curriculum) to support gynecologic oncology fellowships in regions of the world that do not currently have formal training in gynecologic oncology. In India, on the other hand, leaders in world-class gynecologic oncology centers must find a way to meet the training needs of a vast and disparate country.

GAGE mediates radio resistance in cervical cancers via the regulation of chromatin accessibility.

Radiotherapy (RT) resistance is a major cause of treatment failure in cancers that use definitive RT as their primary treatment modality. This study identifies the cancer/testis (CT) antigen G antigen (GAGE) as a mediator of radio resistance in cervical cancers. Elevated GAGE expression positively associates with de novo RT resistance in clinical samples. GAGE, specifically the GAGE12 protein variant, confers RT resistance through synemin-dependent chromatin localization, promoting the association of histone deacetylase 1/2 (HDAC1/2) to its inhibitor actin. This cumulates to elevated histone 3 lysine 56 acetylation (H3K56Ac) levels, increased chromatin accessibility, and improved DNA repair efficiency. Molecular or pharmacological disruption of the GAGE-associated complex restores radiosensitivity. Molecularly, this study demonstrates the role of GAGE in the regulation of chromatin dynamics. Clinically, this study puts forward the utility of GAGE as a pre-screening biomarker to identify poor responders at initial diagnosis and the therapeutic potential of agents that target GAGE and its associated complex in combination with radiotherapy to improve outcomes.

Cervical cancer prevention training in South East Asian LMICs.

The Association of Southeast Asian Nations (ASEAN) is a confederation of 10 sovereign states occupying approximately 1.7 million square miles of Southeast Asia with an estimated population of just under 630 million. Southeast Asia continues to have one of the world's highest rates of cervical cancer-related death. Organised training in cervical cancer screening is essential but lacking in low to middle income countries (LMICs). Systematic training of local doctors is an essential part of an effective screening program and an effective strategy to reduce cervical cancer-related mortality. Singapore is a first-world economy with a healthcare system that can support this mode of training and is geographically proximate to Southeast Asian LMICs that need this training. This makes it possible for model of tiered training with trainers on site in the LMICs and more advanced training where trainees receive training in Singapore. We present a case study where this tiered system of training is applied to Cambodia and demonstrate that this model of training is not only effective but also sustainable.

Clinical outcomes in endometrial cancer care when the standard of care shifts from open surgery to robotics.

INTRODUCTION: In Singapore, the standard of care for endometrial cancer staging remains laparotomy. Since the introduction of gynecologic robotic surgery, there have been more data comparing robotic surgery to laparoscopy in the management of endometrial cancer. This study reviewed clinical outcomes in endometrial cancer in a program that moved from laparotomy to robotic surgery. METHODS: A retrospective review was performed on 124 consecutive endometrial cancer patients. Preoperative data and postoperative outcomes of 34 patients undergoing robotic surgical staging were compared with 90 patients who underwent open endometrial cancer staging during the same period and in the year before the introduction of robotics. RESULTS: There were no significant differences in the mean age, body mass index, rates of diabetes, hypertension, previous surgery, parity, medical conditions, size of specimens, histologic type, or stage of cancer between the robotic and the open surgery groups. The first 20 robotic-assisted cases had a mean (SD) operative time of 196 (60) minutes, and the next 14 cases had a mean time of 124 (64) minutes comparable to that for open surgery. The mean number of lymph nodes retrieved during robot-assisted staging was smaller than open laparotomy in the first 20 cases but not significantly different for the subsequent 14 cases. Robot-assisted surgery was associated with lower intraoperative blood loss (110 [24] vs 250 [83] mL, P < 0.05), a lower rate of postoperative complications (8.8% vs 26.8%, P = 0.032), a lower wound complication rate (0% vs 9.9%, P = 0.044), a decreased requirement for postoperative parenteral analgesia (5.9% vs 51.1, P < 0.001), and shorter length of hospitalization (2.0 [1.1] vs 6.0 [4.5] days, P < 0.001) compared to patients in the open laparotomy group. CONCLUSIONS: Our series shows that outcomes traditionally associated with laparoscopic endometrial cancer staging are achievable by laparoscopy-naive gynecologic cancer surgeons moving from laparotomy to robot-assisted endometrial cancer staging after a relatively small number of cases.