Economic Evaluation of Screening Strategies Combined with HPV Vaccination of Preadolescent Girls for the Prevention of Cervical Cancer in Vientiane, Lao PDR.

BACKGROUND: Several approaches to reduce the incidence of invasive cervical cancers exist. The approach adopted should take into account contextual factors that influence the cost-effectiveness of the available options. OBJECTIVE: To determine the cost-effectiveness of screening strategies combined with a vaccination program for 10-year old girls for cervical cancer prevention in Vientiane, Lao PDR. METHODS: A population-based dynamic compartment model was constructed. The interventions consisted of a 10-year old girl vaccination program only, or this program combined with screening strategies, i.e., visual inspection with acetic acid (VIA), cytology-based screening, rapid human papillomavirus (HPV) DNA testing, or combined VIA and cytology testing. Simulations were run over 100 years. In base-case scenario analyses, we assumed a 70% vaccination coverage with lifelong protection and a 50% screening coverage. The outcome of interest was the incremental cost per Disability-Adjusted Life Year (DALY) averted. RESULTS: In base-case scenarios, compared to the next best strategy, the model predicted that VIA screening of women aged 30-65 years old every three years, combined with vaccination, was the most attractive option, costing 2 544 international dollars (I$) per DALY averted. Meanwhile, rapid HPV DNA testing was predicted to be more attractive than cytology-based screening or its combination with VIA. Among cytology-based screening options, combined VIA with conventional cytology testing was predicted to be the most attractive option. Multi-way sensitivity analyses did not change the results. Compared to rapid HPV DNA testing, VIA had a probability of cost-effectiveness of 73%. Compared to the vaccination only option, the probability that a program consisting of screening women every five years would be cost-effective was around 60% and 80% if the willingness-to-pay threshold is fixed at one and three GDP per capita, respectively. CONCLUSIONS: A VIA screening program in addition to a girl vaccination program was predicted to be the most attractive option in the health care context of Lao PDR. When compared with other screening methods, VIA was the primary recommended method for combination with vaccination in Lao PDR.

The economic evaluation of human papillomavirus vaccination strategies against cervical cancer in women in Lao PDR: a mathematical modelling approach.

BACKGROUND: Cervical cancer, a preventable disease, is the third leading cause of cancer morbidity and mortality in the Lao People's Democratic Republic (Lao PDR). Since many cervical cancers are linked to human papilloma virus (HPV) infection, vaccination against this virus may lead to a reduction in these types of cancer. The study described here is the first to compare the cost-effectiveness of different HPV vaccination options in Lao PDR. METHODS: A dynamic compartment model was created. The model included routine screening activities already in place, as well as theoretical interventions that included a 10-year old girl-only vaccination programme combined with/without a 10-year old boy vaccination programme and/or a catch-up component. The simulation was run over 100 years. In base case analyses, we assumed 70 % vaccination coverage with lifelong protection and 100 % efficacy against HPV types 16/18. The outcomes of interest were the incremental cost per Disability-Adjusted Life Year (DALY) averted. RESULTS: In base case analyses, according to the WHO definition of cost-effectiveness thresholds, vaccinating 10-year-old girls was very cost-effective. Adding a catch-up vaccination element for females aged 11-25 years was also very cost-effective, costing 1559 international dollars (I$) per DALY averted. Increasing the age limit of the catch-up vaccination component to 75 years old showed that this remained a cost-effective option (I$ 5840 per DALY averted). Adding a vaccination programme for 10-year-old boys was not found to be cost-effective unless a short time simulation (30 years or less) was considered, along with a catch-up vaccination component for both males and females. CONCLUSIONS: Adding a catch-up female vaccination component is more attractive than adding a 10-year-old boy vaccination component.

Accuracy of Combined Visual Inspection with Acetic Acid and Cervical Cytology Testing as a Primary Screening Tool for Cervical Cancer: a Systematic Review and Meta-Analysis.

BACKGROUND: The performance of combined testing visual inspection with acetic acid (VIA) and cervical cytology tests might differ from one setting to another. The average estimate of the testing accuracy across studies is informative, but no meta-analysis has been carried out to assess this combined method. OBJECTIVE: The objective of this study was to estimate the average sensitivity and specificity of the combined VIA and cervical cytology tests for the detection of cervical precancerous lesions. MATERIALS AND METHODS: We conducted a systematic review and a meta-analysis, according to the Cochrane Handbook for Systematic Review of Diagnostic Test Accuracy. We considered two cases. In the either-positive result case, a positive result implies positivity in at least one of the tests. A negative result implies negativity in both tests. In the both-positive case, a positive result implies having both tests positive. Eligible studies were identified using Pubmed, Embase, Website of Science, CINHAL and COCRANE databases. True positive, false positive, false negative and true negative values were extracted. Estimates of sensitivity and specificity, positive and negative likelihood (LR) and diagnostic odds ratios (DOR) were pooled using a hierarchical random effect model. Hierarchical summary receiver operating characteristics (HSROC) were generated and heterogeneity was verified through covariates potentially influencing the diagnostic odds ratio. FINDINGS: Nine studies fulfilled inclusion criteria and were included in the analysis. Pooled estimates of the sensitivities of the combined tests in either-positive and both-positive cases were 0.87 (95% CI: 0.83-0.90) and 0.38 (95% CI: 0.29-0.48), respectively. Corresponding specificities were 0.79 (95% CI: 0.63-0.89) and 0.98 (95% CI: 0.96-0.99) respectively. The DORs of the combined tests in either-positive or both-positive result cases were 27.7 (95% CI: 12.5-61.5) and 52 (95% CI: 22.1-122.2), respectively. When including only articles without partial verification bias and also a high-grade cervical intraepithelial neoplasia as a threshold of the disease, DOR of combined test in both-positive result cases remained the highest. However, DORs decreased to 12.1 (95% CI: 6.05-24.1) and 13.8 (95% CI: 7.92-23.9) in studies without partial verification bias for the combined tests in the either-positive and both-positive result cases, respectively. The screener, the place of study and the size of the population significantly influenced the DOR of combined tests in the both-positive result case in restriction analyses that considered only articles with CIN2+ as disease threshold. CONCLUSIONS: The combined test in the either-positive result case has a high sensitivity, but a low specificity. These results suggest that the combined test should be considered in developing countries as a primary screening test if facilities exist to confirm, through colposcopy and biopsy, a positive result.

Outcome and patterns of recurrence for International Federation of Gynecology and Obstetrics (FIGO) stages I and II squamous cell vulvar cancer.

OBJECTIVE: To study patterns of recurrence, to evaluate pathologic features correlating with recurrence, and to estimate the prognostic implications for each different pattern of recurrence in the International Federation of Gynecology and Obstetrics (FIGO) stages I and II squamous cell vulvar cancer. METHODS: This was a retrospective study of 121 cases of vulvar cancer managed at our institution from 1987 to 2005. Time to recurrence, sites of local and distant recurrence, and the type of surgery were recorded. Relapse-free and overall survival were calculated. RESULTS: There was no difference in recurrence rates, time to recurrence, or survival between patients with FIGO stages I or II disease. The 5-year actuarial survival (corrected for competing risks) for stage I disease was 97% compared with 95% for stage II (P=.83). Progression-free survival at 5 years was 86% for stage I and 94% for stage II.In this study, 95.9% of patients were treated with vulvar-conserving surgery without detriment with respect to recurrence or survival. CONCLUSION: Vulvar-conserving surgery, even for large tumors, results in excellent outcomes. Vulvar recurrences have an excellent prognosis, but primary site and remote site vulvar recurrences are biologically different. There is no justification for the FIGO differentiation of node-negative cancers confined to the vulva on the basis of tumor size. LEVEL OF EVIDENCE: III.

Triage of ovarian masses.

BACKGROUND: Triage of ovarian masses for appropriate management is important in ensuring the best outcome for patients. The Risk of Malignancy Indices (RMI) seem to represent a low cost and effective tool for triage and management of women with ovarian masses. AIM: To review patients with an ovarian mass referred to the Gynaecological Cancer Centre at the Royal Hospital for Women, and to assess the effectiveness of the RMI in differentiating benign from malignant tumours in this group of patients. METHODS: A retrospective review of the case records of all patients with an ovarian mass referred to our centre from January 2003 to December 2005 was undertaken. RESULTS: Two hundred and four patients were eligible for RMI calculation. An RMI of < 200 correctly identified 83 of 108 (77%) benign ovarian tumours. An RMI of > 200 correctly identified 11 of 19 (58%) borderline ovarian tumours and 70 of 77 (91%) invasive ovarian tumours. An RMI of > 200 had a sensitivity of 84%, specificity of 77%, positive predictive value of 76% and negative predictive value of 85% in detecting both borderline and invasive ovarian tumours. The false negative rate for invasive tumours was 9%. CONCLUSIONS: This study showed that using RMI at a cut-off of 200 for referral could have prevented 83 benign cases (41%) from being referred. We propose that the RMI could be utilised as a triage tool for referral of ovarian masses to gynaecological cancer centres.

Thromboembolic complications in patients with clear cell carcinoma of the ovary.

OBJECTIVE: The purpose of this study was to define the incidence of deep venous thrombosis (DVT) and pulmonary embolism (PE) in patients with clear cell carcinoma (CCC) of the ovary and to investigate the prognostic factors in such patients. METHODS: Between January 1987 and December 2003, 641 women with primary invasive epithelial ovarian cancer underwent treatment at the Royal Hospital for Women in Sydney, Australia. Sixty-six patients (10.3%) with CCC were identified from the data bank, and their data were compared with a matched-control group of 132 patients with non-clear cell epithelial ovarian carcinoma. RESULTS: A thromboembolic event (DVT or PE) was noted in 27.3% of patients with CCC, compared to 6.8% of patients with other epithelial ovarian cancers. PE was detected in 13.6% and 3.8% of patients, respectively. In patients with CCC, DVT was frequently observed before operation or at the time of recurrence. In a multivariate analysis of patients matched for age and stage, the occurrence of a DVT or the presence of endometriosis was significant predictors of clear cell histology. Within the clear cell group, no particular risk factor for DVT could be identified. Metastases of 50 mm or greater in diameter, ascites of 1000 ml or more, advanced FIGO stage, and the occurrence of DVT were poor prognostic factors for CCC in univariate analysis, but in a multivariate Cox regression analysis, only FIGO stage and occurrence of DVT remained significant. CONCLUSION: The incidence of venous thromboembolic events was found to be significantly higher in patients with CCC when compared to patients with other epithelial ovarian cancers.

A new prognostic model for FIGO stage 1 epithelial ovarian cancer.

BACKGROUND: No consensus exists which patients with surgical stage 1 epithelial ovarian should receive postoperative chemotherapy. The purpose of this study was to evaluate the prognostic impact of preoperative CA-125 and to establish a prognostic index to identify patients in different risk categories. METHODS: Data of 600 surgically staged patients with FIGO stage 1 EOC treated in eleven gynecological cancer centers in Australia, the USA and Europe were analyzed. Eligible patients include those with invasive EOC where a preoperative CA-125 was obtained and standard surgical staging performed. Overall survival (OS) was chosen as study endpoint. Preoperative CA-125 values were compared with other prognostic factors, and univariate and multivariate Cox models were calculated. RESULTS: Two hundred and one patients (33.5%) had preoperative CA-125 < or =30 U/ml and CA-125 levels < or =30 U/ml were associated with lower grade, sub-stage 1A and mucinous histologic cell type. Patients with elevated CA-125 levels were more likely to receive chemotherapy. OS probability was 95% and 85% for patients with pretreatment CA-125 < or =30 U/ml and >30 U/ml, respectively (p 0.003). Multivariate analysis confirmed preoperative serum CA-125 >30 U/ml (OR 2.7) and age at diagnosis >70 years (OR 2.6) as the only independent predictors for overall survival. CONCLUSION: Pretreatment of CA-125 < or =30 U/ml dominates over histologic cell type, sub-stage and grade to identify a subgroup of FIGO stage 1 patients with a genuinely good prognosis with extremely good survival and who could possibly be spared with adjuvant chemotherapy.

Prognostic importance of preoperative CA-125 in International Federation of Gynecology and Obstetrics stage I epithelial ovarian cancer: an Australian multicenter study.

PURPOSE: To evaluate the prognostic significance of preoperative CA-125 levels on overall survival of patients with International Federation of Gynecology and Obstetrics (FIGO) stage I epithelial ovarian cancer (EOC). PATIENTS AND METHODS: Data from 518 patients with FIGO stage I EOC treated in seven gynecologic oncology centers throughout Australia between 1990 and 2002 were analyzed. Patients with borderline tumors and nonepithelial ovarian carcinomas were excluded, as were women in whom CA-125 had not been determined preoperatively. Preoperative CA-125 levels were studied in surgically staged and incompletely staged patients and compared with prognostic factors, such as substage, grade, and histologic type. Multivariate Cox models were calculated. RESULTS: CA-125 levels more than 30 U/mL were associated with higher grade, substage 1B and 1C, nonmucinous histologic type, and older age. In univariate analysis, higher histologic grade, the absence of surgical staging, and preoperative CA-125 levels more than 30 U/mL were associated with impaired survival. Multivariate analysis identified histologic grade, preoperative CA-125, and surgical staging as independent predictors for survival. In the subgroup of completely surgically staged patients, the 5-year overall survival rate was 82% (95% CI, 76% to 88%) for patients with CA-125 levels more than 30 U/mL and 95% (95% CI, 90% to 99%) for patients with CA-125 levels of 30 U/mL or less (P = .028). In the group of incompletely staged patients, the 5-year survival rates were similar for patients with elevated and normal serum CA-125 levels. CONCLUSION: Complete surgical staging, histologic grade, and preoperative serum CA-125 levels are independent prognostic factors and should be included in the decision making for chemotherapy.

Presenting symptoms of epithelial ovarian cancer.

OBJECTIVES: Epithelial ovarian cancer is a common disease with a high mortality, the latter being frequently attributed to late diagnosis due to failure to recognise symptoms of early disease. This study was designed to determine any differences in symptomatology between patients with early and advanced stage disease. DESIGN: A retrospective cohort study of 100 patients with stage 1 disease and 100 with stage 3 disease. Ten consecutive patients with stage 1 disease and 10 with stage 3 disease were identified from the database of patients treated each year from 1990 to 1999. SETTING: A tertiary referral centre for gynecological malignancy. OUTCOME MEASURES: The nature and duration of symptoms, age at presentation, and the size, histologic type and grade of tumour were determined by chart review, and the findings compared using logistic regression analysis. RESULTS: Ninety percent of women with early, and 100% with advanced disease reported at least one symptom. With early disease, abdominal pain was reported by 51% and abdominal swelling by 32%, and with advanced disease abdominal swelling by 62% and abdominal pain by 44%. Seventy percent of the early stage and 69% of the advanced stage cohorts reported symptoms of less than 3 months duration. Tumours less than 5 cm diameter were three times more likely to have advanced disease (P = 0.02). Grade 1 tumours were 40 times more likely to be early stage than grade 3 tumours. Serous tumours occurred in 25% of patients with early disease, and 45% with advanced disease (P = 0.01). CONCLUSION: Patients with early stage ovarian cancer are likely to be younger and to have larger, better differentiated tumours that are more often non-serous histologically. Advanced disease is not invariably due to delayed diagnosis.

Fertility effects of cancer treatment.

BACKGROUND: Cancer sufferers are a subfertile group, and most treatments have the potential to adversely affect gonadal function. As cancer treatment becomes more effective and survival rates improve there are more cancer survivors in the reproductive age group for whom parenting is an important consideration. OBJECTIVE: This article outlines the effects on fertility of cancer treatments and techniques to minimise the risk of infertility. DISCUSSION: The overall prospects for younger cancer sufferers to either retain their fertility or have genetic offspring is now better than ever before, due to advances in assisted reproductive technology, the appropriate use of fertility sparing surgery and other techniques to reduce the toxicity of therapy on the reproductive organs. These advances raise new moral and ethical concerns that must be considered before advising cancer sufferers of the options for preserving reproductive capacity.