Objective: Triage testing is an integral part of high-risk human papillomavirus (HPV)-based cervical screening programs. This study assesses, from a healthcare payer perspective in Singapore, the cost-effectiveness of p16/Ki-67 dual-stained cytology (DS) compared to current standard of care (SOC). Methods: A decision-analytic Markov microsimulation model with a lifetime horizon was built to simulate the outcomes from HPV screening in Singaporean women aged 30–65 years. The intervention (primary testing with HPV genotyping followed by DS reflex test) was compared to current SOC (HPV genotyping followed by cytology) according to Singaporean clinical management guidelines. The progression through health states and associated costs and health outcomes were based on local clinical care data in Singapore. Screening impact was assessed by cost saving, number of colposcopy and quality-adjusted life years (QALYs). Results: Compared to SOC, implementation of HPV genotyping + DS was estimated to decrease the number of screening test (−2.02 times per patient) and colposcopy (−0.16 times per patient), and reduce the overall costs to the Singaporean healthcare system by S$225.59 per patient (95% confidence interval [CI]=S$199.05 to S$249.99). The total QALYs estimates for the 2 approaches were similar (−0.0003; 95% CI=−0.0031 to 0.0022). Sensitivity analyses confirmed the robustness of expected cost-savings and that the full value of avoided colposcopies may be larger than projected in the current analysis. Conclusion This economic modelling analysis projected that using DS instead of conventional cytology as the reflex test for positive test with non-HPV-16/18 subtypes significantly reduced the financial costs of cervical cancer screening in Singapore.

INTRODUCTIONCervical cancer is the tenth most common cancer and the eighth most frequent cause of death among women in Singapore. As human papillomavirus (HPV) infection is the necessary cause of cervical cancer, the risk of cervical cancer can be substantially reduced through vaccination. This study was conducted to evaluate the cost-effectiveness of two-dose HPV vaccination as part of a national vaccination programme for 12-year-old girls in Singapore, from the perspective of the healthcare payer.

METHODSA lifetime Markov cohort model was used to evaluate the cost-effectiveness of introducing the AS04-adjuvanted HPV-16/18 vaccine (AS04-HPV-16/18v) to the current cervical screening programme in Singapore. Furthermore, the cost-effectiveness of the AS04-HPV-16/18v was compared with the HPV-6/11/16/18 vaccine (4vHPV). Model inputs were derived from local data, where possible, and validated by clinical experts in Singapore.

RESULTSIntroduction of the AS04-HPV-16/18v in Singapore was shown to prevent 137 cervical cancer cases and 48 cervical cancer deaths when compared with screening alone. This resulted in an incremental cost-effectiveness ratio of SGD 12,645 per quality-adjusted life year (QALY) gained, which is cost-effective according to the World Health Organization threshold for Singapore. When discounted at 3%, AS04-HPV-16/18v was dominant over 4vHPV, with cost savings of SGD 80,559 and 28 additional QALYs gained. In the one-way sensitivity analysis, AS04-HPV-16/18v remained cost-effective compared with screening alone and dominant compared with 4vHPV.

CONCLUSIONAS04-HPV-16/18v is the most cost-effective choice for reducing the burden of cervical cancer through universal mass vaccination for 12-year-old girls in Singapore.

INTRODUCTIONThis study aimed to determine the prevalence of cervical intraepithelial neoplasia grade 3 or worse (≥CIN3) and cost-effectiveness of human papillomavirus (HPV) genotyping with reflex liquid-based cytology (LBC) for cervical cancer screening in Singapore.

MATERIALS AND METHODSWomen who were ≥25 years old and undertook co-testing with LBC and HPV-genotyping (Cobas-4800, Roche, USA) for HPV-16, HPV-18 and 12 high-risk HPV types in a single institution were studied retrospectively. A single cervical smear in ThinPrep® PreservCyt® solution (Hologic, USA) was separated for tests in independent cytology and molecular pathology laboratories. The results were reviewed by a designated gynaecologist according to institutional clinical management protocols. Those who tested positive for HPV-16 and/or HPV-18 (regardless of cytology results), cytology showing low-grade squamous intraepithelial lesions (LSIL) or high-grade SIL (HSIL), or atypical squamous cells of undetermined significance (ASCUS) with positive 12 high-risk HPV types were referred for colposcopy. Colposcopy was performed by experienced colposcopists. Cervical biopsy, either directed punch biopsies or excisional biopsy, was determined by a colposcopist. The diagnosis of ≥CIN3 was reviewed by a gynaecologic pathologist. Cost-effectiveness of HPV-based screening in terms of disease and financial burden was analysed using epidemiological, clinical and financial input data from Singapore.

RESULTSOf 1866 women studied, 167 (8.9%) had abnormal cytology (≥ASCUS) and 171 (9.2%) tested positive for high-risk HPV. Twenty-three CIN were detected. Three of the 10 ≥CIN3 cases had negative cytology but positive HPV-16. Compared to cytology, HPV genotyping detected more ≥CIN3 (OR: 1.43). HPV+16/18 genotyping with reflex LBC was superior in terms of cost-effectiveness to LBC with reflex HPV, both for disease detection rate and cost per case of ≥CIN2 detected.

CONCLUSIONCompared to cytology, HPV+16/18 genotyping with reflex LBC detected more ≥CIN3 and was cost-effective for cervical screening in Singapore.