Costs of detection and treatment of cervical cancer,cervical dysplasia and genital warts in the UK

ABSTRACT

Objective: Infection with human Papillomavirus (HPV) is a necessary cause of cervical cancer (CC) and genital warts (GW). HPV vaccination studies have shown excellent efficacy against HPV-induced lesions. To assess the cost-effectiveness of a HPV quadrivalent (6, 11, 16 and 18) vaccine it is necessary to estimate the costs of managing current levels of HPV-related diseases. This study estimates the annual 2003 expenditures in the UK for CC screening, follow-up of abnormal findings, CC treatment and GW treatment.

Design and methods: CC screening programmes provided the annual number of screening tests, their results and use of colposcopy procedures in women with abnormal findings. Incident CC cases and hospital admissions for CC in 2003 were used to estimate CC costs. Health Protection Agency data provided the annual number of new, recurrent or persistent cases of GW treated in Genitourinary Medicine (GUM) clinics. Treatment patterns for managing GW were estimated by GUM clinicians. The annual physician visits, tests, procedures, hospital admissions and topical genital wart medications were costed to estimate the total annual expenditures for CC and GW.

Results: There were 4.8 million screening tests and 230?303 colposcopy procedures. Estimated costs for screening, management of abnormal and inadequate findings were £138.5 million. Annual management costs for incident and prevalent CC cases were £46.8 million. There were an estimated 76?457 incident and 55?657 recurrent/persistent GW cases in 2003. The costs for managing these cases were approximately £22.4 million. Total annual estimated costs for CC screening, management and treatment of GW were £208 million and ranged from £186.9 to £214 million based upon sensitivity analyses.

Conclusions: The direct medical costs for the NHS associated with detection and management of CC, cervical dysplasia and treatment of GW in the UK are substantial. These medical costs are invaluable for future cost-effectiveness analyses of a quadrivalent HPV vaccine programme.     

Optimum treatment of genital warts

Genital warts (condylomata acuminata) must be treated and controlled carefully because of their frequent relapses and the risk of malignancy. Treatment is by destruction of the lesions. The most frequently used treatment for external warts is podophyllin 20% in ethanol which is applied to the affected area and then carefully washed off after 4 to 6 hours. The effectiveness of this method of treatment varies between 20 and 98%, with the warts generally disappearing in 3 to 4 days. If podophyllin is ineffective or is contraindicated (e.g. in pregnancy), other measures such as surgical removal, electrocautery, cryo-surgery or laser treatment can be used independently or in combination. Other treatments that have been used include topical application of 5-fluorouracil and intralesional or systemic use of interferons. Patients and their sexual partners should be followed for several months after treatment. A Papanicolaou smear should be obtained from women prior to treatment because of the association of human papilloma virus infection with cervical invasive neoplasia.     

尖锐湿疣的病理特点及临床治疗分析

目的 探讨诊断尖锐湿疣的病理特点及临床治疗分析.方法 对125例尖锐湿疣患者病理特点进行研究分析.结果 显示出尖锐湿疣发病原因.结论 尖锐湿疣的病理特点及临床治疗,需多种病理因素与临床的结合.     

Section Review: Biologicals & Immunologicals: Human papillomavirus infection,genital warts and cervical cancer: prospects for prophylactic and therapeutic vaccines

Papillomaviruses cause warts of the skin, anogenital mucosa, and bronchial mucosa, and also pre-neoplastic lesions of the cervical and vulval mucosae, which in a proportion of women progress to invasive carcinomata. Papillomaviruses cannot be propagated in vitro, which has hindered the development of prophylactic vaccines, but recent production of synthetic virus like particles (VLPs) in vitro using recombinant DNA technology has resulted in vaccines which prevent papillomavirus infection in animal models, and has given rise to commercial interest in human prophylactic vaccines. Papillomavirus proteins are generally poorly presented to the immune system in the course of natural infection and, therefore, therapeutic immunity may be produced by appropriate choice of viral protein and delivery system. Immunotherapy for PV associated cancer is targeted at two non-structural PV proteins expressed in cancer cells (E6 and E7), which have been shown to be effective targets for immunotherapy in experimental tumour models: Phase I/II clinical trials are now underway. Immunotherapy for pre-neoplastic lesions presents a greater choice of potential viral antigenic targets: as animal models give conflicting data, clinical trials in man may be necessary to choose the correct antigens.     

阿维A辅助治疗复发性尖锐湿疣临床观察

目的：探讨阿维A辅助治疗复发性尖锐湿疣临床效果及安全性。方法选取本院近年来收治复发性尖锐湿疣患者70例,随机分为对照组和阿维A组,每组各35例;其中对照组采用常规对症治疗;阿维A组在对照组治疗基础上,加用阿维A口服治疗;比较两组患者临床复发率,治疗前后血清细胞因子水平及不良反应发生率等。结果阿维A组患者治疗后1个月、3个月及6个月临床复发率均显著低于对照组（ P＜0.05）;对照组和阿维A组患者治疗后IL-4、IL-10及IFN-γ等细胞因子水平均显著优于治疗前,且阿维A组患者细胞因子水平改善程度均显著优于于对照组（ P＜0.05）;阿维A组患者皮肤不适及口干发生率均显著高于对照组,但皮肤溃烂发生率显著低于对照组（P＜0.05）。结论阿维A辅助治疗复发性尖锐湿疣可有效降低临床复发风险,改善机体细胞因子水平,提高机体免疫力,且无严重不良反应。     

Polyhexamethylene biguanide for treatment of external genital warts: a prospective, double-blind, randomized study

Genital human papillomavirus infection is one of the most common sexually transmitted diseases. Polyhexamethylene biguanide is a new agent, that has been demonstrated to have potent in vivo antiviral effects in animal and in human models. The present prospective, double-blind, randomized, placebo (vehicle-controlled) trial evaluated the efficacy and safety of daily patient-applied polyhexamethylene biguanide for up to 16-weeks for the treatment of external genital warts. Wart recurrence was investigated during a 12-week treatment-free follow-up period. In the intent-to-treat analysis, baseline warts cleared from 49 of 94 (52%) patients treated with polyhexamethylene biguanide cream versus and 3 of 95 (4%) placebo patients; the differences between the groups treated with placebo and polyhexamethylene biguanide were significant (P < 0.0001). For subjects who completed the follow-up period, recurrence rates after a complete response were 19% (9 of 48 patients) in the polyhexamethylene biguanide cream group, 17% cream group, and 0% (0 of 3) in the placebo group. There were no systemic reactions, although local skin reactions (generally of mild or moderate severity) were common in the polyhexamethylene biguanide cream group. Local reactions caused two patients to discontinue treatment. The most frequently reported local skin reactions were erythema, excoriation or flaking, and erosion. Patient-applied polyhexamethylene biguanide cream is effective for the treatment of external genital warts and has a favorable safety profile.     

Economic and humanistic burden of external genital warts

External genital warts (EGW) are a sexually transmitted infection caused by various strains of human papillomavirus (HPV). Several studies have described the direct and indirect costs of EGW, while others have reported on the burden of EGW in terms of the impact on the quality of life (QOL) of patients. The arrival of a quadrivalent HPV vaccine that protects against both cervical cancer and EGW requires a proper understanding of the impact of vaccines on costs and QOL. Using pre-defined search terms and inclusion/exclusion criteria, we performed a systematic review of the economic and humanistic burden of EGW. The focus of our review was on literature describing the direct and indirect costs of EGW per episode of care (EoC) or per year, as well as the impact of EGW on disease-specific, generic, or preference-based QOL measures. We also reviewed the literature on the national economic burden of EGW from the perspectives of different countries. Other aspects of EGW management that can inform economic modelling studies, such as length of EoC, number of physician visits and indirect costs, were also explored. Our review sheds light on the high economic and humanistic burden of EGW and important differences in the costs between men and women, as well as the differences in health resource utilization and costs across countries. Our study also highlights the dearth of information on the impact of EGW on the QOL and productivity of patients.     

高频电刀联合膦甲酸钠和咪喹莫特乳膏治疗女性尖锐湿疣

目的观察高频电刀联合膦甲酸钠和咪喹莫特乳膏治疗女性尖锐湿疣的疗效。方法将130例女性尖锐湿疣患者分成3组,A组采用单纯高频电刀治疗;B组采用高频电刀治疗,患处涂咪喹莫特乳膏;C组在B组治疗方案的基础上给予膦甲酸钠。三组治疗结束后随访6个月,比较三组的复发率。结果 A组复发率为37.14%,B组为27.19%,C组为15.38%,3组比较均有显著性差异。结论高频电刀联合膦甲酸钠和咪喹莫特乳膏治疗女性尖锐湿疣复发率低,不良反应少。     

Treatment patterns and associated costs for genital warts in Italy

ABSTRACT

Objective: Genital warts are caused by human papillomavirus (HPV), principally types 6 and 11, and are highly contagious. This study assessed treatment patterns and costs of management of genital warts in Italy.

Research design and methods: This was a retrospective, observational study conducted among gynaecologists, dermatologists, and specialists at sexually transmitted disease clinics in Italy. Resource-use data related to genital warts were collected for patients at risk in the age range 14–64 years examined during 2005. Unit costs were assigned to resource use to provide estimates of the direct, indirect and total costs per case of genital warts.

Results: Twenty-eight investigators enrolled 341 patients aged 15–64 years, including 194 (56.9%), 81 (23.7%) and 66 (19.4%) patients with newly diagnosed, recurrent and resistant genital warts, respectively. Most patients (333/341; 97.7%) had at least one outpatient visit, while 43 (12.6%) patients were hospitalised, including 39 patients without an overnight stay (day-hospital cases, 11.4%). Self-applied medication was prescribed for 124 (36.4%) patients. Most outpatient cases (267/333; 80.2%) underwent an office-based procedure. Mean annual direct medical costs per patient, which were funded predominantly by the Italian National Health Service (there was some patient co-payment), were €242 for men and €332 for women. When productivity losses were included, mean total annual costs were €325 for men and €464 for women.

Conclusions: This is the first study of treatment patterns and costs for genital warts in Italy. Treatment patterns differ in some respects from those observed in other European countries, but costs generally appear similar. Despite the limitations of physician selection bias and over-representation of North Italy in the patient sample, the findings of this study may be useful in estimating the cost-effectiveness of introducing a quadrivalent HPV vaccination programme in Italy.     

CA在综合干预后依从性和复发的体会

目的 了解患者应用a-2b干扰素依从性差的原因,观察综合干预对患者治疗依从性及尖锐湿疣（CA）复发率的影响.方法 将133例CA患者随机分为干预组67例和对照组66例.对照组按常规给予健康教育及常规治疗,干预组除常规健康教育外,实施全程治疗护理干预.观察2组临床疗效和依从性.结果 干预组遵医行为优于对照组,临床疗效优于对照组,复发率低于对照组,差异均有统计学意义（P＜0.01）.结论 综合干预可明显提高CA患者治疗的依从性,降低CA的复发率.     

Costs of irritable bowel syndrome in the UK and US

Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, with an estimated prevalence rate in the general population of 10-15% in industrialised countries. Although IBS is not a life-threatening disease, it contributes significantly to a large segment of healthcare resource consumption. This review provides an overview of studies addressing the direct and indirect costs of IBS in the US and the UK. A systematic literature search was conducted in MEDLINE and the Cochrane library; additionally, all reference lists covering the years from 1960 to May 2004 were scanned. Twenty-four publications for the US and the UK, published between 1991 and 2003, were identified: 6 were excluded, 18 were included. Data for the UK, US and UK + US were reported in 5, 11 and 2 publications, respectively. Total direct cost estimates per patient per year ranged from US 348 dollars to US 8750 dollars (calculated for year 2002). The average number of days off work per year because of IBS was between 8.5 and 21.6; indirect costs ranged from US 355 dollars to US 3344 dollars. The total costs and cost components of IBS are influenced by several factors: features of the investigated patient group (age, limitation to healthcare seekers or all IBS patients, comorbidity, severity of symptoms), database used, method of data collection (retrospective or prospective, varying cost components, time-point of data collection in relation to index-date of IBS diagnosis, method of cost calculation [incidence or prevalence based]) and different healthcare systems in the US and the UK. These factors led to the incomparability of published data, thus no comprehensive picture can be drawn of the total costs related to IBS in the UK and US. Data underline the magnitude of the economic impact of IBS in the UK and US, which is increased by a factor of 1.1-6.0, compared with matched non-IBS control groups. IBS contributes both direct and indirect costs to the total healthcare bill. Further studies should take influencial factors into account and report related data carefully in order to provide useful and comparable published cost data. Additionally, further research on the cost effectiveness of diagnostic procedures and therapies in IBS is required to define strategies to help IBS patients improve their quality of life and reduce related costs.     

宫颈癌的筛查、早期诊断与治疗

1宫颈癌的筛查方法巴氏细胞学检查,即宫颈刮片细胞学检查,又名巴氏涂片法(Pap Smear),是以该检查方法的发明者George Papanicolaou博士的名字命名的。1943年,Papanicolaou和Traut发表了著名的宫颈细胞学论文,首次将宫颈细胞学检查作为宫颈癌的一种筛查方法。此后,巴氏涂片就成为了宫颈癌筛查中最常用的一种方法。迄今,其已经应用     

Colposcopy in the management of cervical dysplasia

A follow-up study was carried out on 27 patients with high dysplasia and 133 patients with mild dysplasia for at least 1 year, using mainly cytodiagnosis and colposcopy. Advanced cases were identified in 25.9% of the first group and 8.3% in the latter group. It was demonstrated that these advanced cases could be found without fail from colposcopic findings combined with cytodiagnosis.     

腹腔镜宫颈癌根治术治疗早期宫颈癌的效果

目的 探讨腹腔镜宫颈癌根治术对早期宫颈癌的治疗效果。方法 选取2019年10月至2021年3月辽宁省健康产业集团抚矿总医院收治的110例早期宫颈癌患者作为研究对象,按照随机数字表法分为试验组与对照组,各55例。试验组采用腹腔镜宫颈癌根治术治疗,对照组采用开腹宫颈癌根治术治疗。比较两组的术后并发症总发生率、术后恢复饮食时间、住院时间及排气时间以及手术满意度。结果 试验组的术后并发症总发生率低于对照组,差异有统计学意义（P<0.05）。试验组术后恢复饮食时间及排气时间均早于对照组,住院时间短于对照组,差异有统计学意义（P<0.05）。试验组的手术满意度高于对照组,差异有统计学意义（P<0.05）。结论 对于早期宫颈癌患者的临床治疗,采用腹腔镜宫颈癌根治术可以有效地减少患者的并发症,提升患者对于手术的满意度水平,值得在临床上大力宣传。     

Topical imiquimod: a review of its use in genital warts.

Imiquimod is a topically active immunomodulatory agent that is formulated as a 5% cream for application by the patient. It is the first agent of its class, the immune response modifiers, to be used in the treatment of genital warts. In immunocompetent patients with genital warts, imiquimod stimulates the production of interferon-alpha and various other cytokines, and has indirect antiviral activity. In randomised, double-blind, vehicle-controlled clinical trials, complete clearance of warts occurred in 37 to 50% of immunocompetent patients with genital warts treated with imiquimod 5% cream 3 times a week for up to 16 weeks; partial clearance of warts (defined as a reduction in wart area of > or = 50%) was observed in 76% of recipients of imiquimod 5% cream. Rates of complete or partial clearance of warts were significantly higher in patients who applied imiquimod 5% cream 3 times a week than in recipients of imiquimod 1% or vehicle cream, each applied 3 times a week. A between-gender difference in clinical response to imiquimod 5% cream has been reported, with female patients experiencing higher rates of complete clearance of warts than males. Recurrence(s) of > or = 1 wart occurred in 13 to 19% of immunocompetent patients in whom complete clearance of warts had been achieved with imiquimod 5% cream. Imiquimod 5% cream also shows some clearance of warts in immunosuppressed HIV-infected patients with genital warts. Preliminary results of a vehicle-controlled study showed that the rate of partial clearance of warts (defined as a reduction in baseline wart area of >50%) [38%] was significantly higher with imiquimod 5% cream than with vehicle cream; however, the rate of complete clearance was not significantly higher than with vehicle cream. Imiquimod 5% cream is generally well tolerated by immunocompetent and HIV-infected patients. Local skin reactions (mainly mild or moderate), including erythema, itching and burning, are the most commonly reported adverse events, occurring in < or = 67% of patients applying imiquimod 5% cream 3 times a week. The incidence of adverse events is lower in patients applying the cream 3 times a week than with daily application. The incidence of systemic adverse events with imiquimod 5% cream (applied daily or 3 times a week) is similar to that of vehicle cream. The tolerability profile of imiquimod cream appears favourable compared with that of podophyllotoxin. CONCLUSION: Imiquimod 5% cream is a new therapeutic option for patients with genital warts. It produces clearance rates broadly similar to those of other treatment approaches and rates of wart recurrence compare favourably with those reported for established treatments. In contrast to most alternative treatment strategies. which are administered in the physician's office, imiquimod cream is a self-administered therapy for outpatient use.     

Costs and consequences of using pamidronate compared with zoledronic acid in the management of breast cancer patients in the UK

OBJECTIVE: To estimate the costs and consequences of using pamidronate compared to zoledronic acid in the prophylactic management of skeletal morbidity among breast cancer patients in the UK. DESIGN AND SETTING: This was a modelling study performed from the perspective of the UK's National Health Service (NHS). METHODS: Published clinical outcomes from a comparative study were combined with resource utilisation estimates derived from a panel of clinicians. This enabled the construction of a decision model depicting the management of patients with breast cancer receiving antineoplastic therapy who are 18 years of age or above and who have at least one bone metastasis (lytic or mixed). There are no significant differences in outcome between using pamidronate and zoledronic acid in breast cancer patients. Therefore, a cost minimisation analysis was performed to identify the treatment strategy that achieves the same outcome for least cost. The expected time attributable to a pamidronate and zoledronic acid infusion was also estimated. MAIN OUTCOME MEASURES AND RESULTS: Starting treatment with pamidronate among patients receiving chemotherapy is expected to lead to a healthcare cost of 6046 pounds over 12 months compared to 6981 pounds with zoledronic acid. In comparison, for patients receiving hormonal therapy, starting treatment with pamidronate is expected to lead to a healthcare cost of 5401 pounds over 12 months compared to 6043 pounds with zoledronic acid. This cost difference is primarily due to the lower acquisition cost of pamidronate and fewer tests among pamidronate-treated patients. Accordingly, pamidronate affords a less expensive management modality. Multivariate analysis showed the expected time attributable to a pamidronate infusion to be 110 to 277 minutes compared with 136 to 296 minutes for a zoledronic acid infusion. CONCLUSION: Use of pamidronate instead of zoledronic acid affords an economic benefit to the NHS. Moreover, published clinical trials show no statistical difference between pamidronate and zoledronic acid at 1 year. Hence, within the limitations of our model and the published evidence, pamidronate is the preferred first-line intravenous bisphosphonate for use in breast cancer patients receiving antineoplastic therapy who are 18 years of age or above and who have at least one bone metastasis (lytic or mixed).     

Costs and consequences of using pamidronate compared with zoledronic acid in the management of breast cancer patients in the UK

ABSTRACT

Objective: To estimate the costs and consequences of using pamidronate compared to zoledronic acid in the prophylactic management of skeletal morbidity among breast cancer patients in the UK.

Design and setting: This was a modelling study performed from the perspective of the UK's National Health Service (NHS).

Methods: Published clinical outcomes from a comparative study were combined with resource utilisation estimates derived from a panel of clinicians. This enabled the construction of a decision model depicting the management of patients with breast cancer receiving antineoplastic therapy who are 18 years of age or above and who have at least one bone metastasis (lytic or mixed). There are no significant differences in outcome between using pamidronate and zoledronic acid in breast cancer patients. Therefore, a cost minimisation analysis was performed to identify the treatment strategy that achieves the same outcome for least cost. The expected time attributable to a pamidronate and zoledronic acid infusion was also estimated.

Main outcome measures and results: Starting treatment with pamidronate among patients receiving chemotherapy is expected to lead to a healthcare cost of £6046 over 12 months compared to £6981 with zoledronic acid. In comparison, for patients receiving hormonal therapy, starting treatment with pamidronate is expected to lead to a healthcare cost of £5401 over 12 months compared to £6043 with zoledronic acid. This cost difference is primarily due to the lower acquisition cost of pamidronate and fewer tests among pamidronate-treated patients. Accordingly, pamidronate affords a less expensive management modality. Multivariate analysis showed the expected time attributable to a pamidronate infusion to be 110 to 277 minutes compared with 136 to 296 minutes for a zoledronic acid infusion.

Conclusion: Use of pamidronate instead of zoledronic acid affords an economic benefit to the NHS. Moreover, published clinical trials show no statistical difference between pamidronate and zoledronic acid at 1 year. Hence, within the limitations of our model and the published evidence, pamidronate is the preferred first-line intravenous bisphosphonate for use in breast cancer patients receiving antineoplastic therapy who are 18 years of age or above and who have at least one bone metastasis (lytic or mixed).     

Gentamicin in the treatment of lower genital tract infections: level of the drug in menses, cervical mucus and vaginal fluid.

The concentration of gentamicin in serum, menses, cervical mucus and vaginal fluid of 39 women under treatment with this antibiotic (80 mg every 8 hr i. m.) was tested by the agar diffusion method. The levels of the drug in the serum varied from 1.88-5.41 micrograms/ml with a peak one hour after the last dosage. In the menses the levels ranged from 2.06-5.87 micrograms/ml with a peak also one hour after the last dosage. The concentration of gentamicin in the cervical mucus and vaginal fluid varied from 0.67-5.14 micrograms/ml and 0.63-6.43 micrograms/ml with a peak three hours after the last administration of the drug. Results are briefly discussed.