Cancer prevention in primary care. Screening for cervical cancer.

Cervical screening has been shown to be effective in several countries, although not by means of randomised controlled trials. A screening programme has been in operation in the United Kingdom since 1964, but it has, in the past, been beset with problems of organisation, accountability, and commitment. The introduction in 1988 of a systematic call and recall introduction in 1988 of a systematic call and recall system and the setting up of an NHS cervical screening programme national coordinating network has brought a greater sense of coherence. Coverage of the target population in England between 1989-90 and 1992-3 increased from 61% to 83%, and there is a strong indication that cervical screening is now beginning to reach those most at risk--namely, older women from lower social classes. Primary care is central to the overall success of the cervical screening programme. General practitioners are in a unique position to invite women for a smear test, to take smears, to ensure that abnormal smear test results are followed up, and to check on reasons for non-attendance. Numerous studies have looked at the involvement of general practice in cervical screening, identifying many ways in which the programme can be improved. Many practices are now running well organised and effective programmes.     

Screening for the prevention of cervical cancer in the era of human papillomavirus vaccination: an Australian perspective

Australia has a unique and highly successful screening program for cervical cancer which is based on the conventional Pap smear. Since its introduction in 1991 there has been a decline in both the incidence of and mortality from this disease. Part of the success of this program has been the introduction of Pap test registers and strict quality assurance measures for cervical cytology, including compulsory key performance indicators for laboratories. Using these measures, nationwide calculations give cervical cytology in Australia a sensitivity of 78% for high-grade lesions and a positive predictive value (PPV) of 78%. Australia was the first country to introduce a widespread government-funded human papillomavirus (HPV) vaccination program in 2007. Because of the high accuracy of Australian cytology, HPV testing alone, given its low PPV and high cost, is unlikely to be a viable alternative to cytology for primary screening in this country. Australia therefore faces unique issues and choices in integrating its extensive vaccination program with a successful cervical screening program.     

When time is of the essence: choosing a currency for prey-handling costs

1.  Heartbeat rate was measured in shore crabs Carcinus maenas (L.) feeding on mussels Mytilus edulis L. in order to estimate the energetic cost of handling prey and to assess the relative importance of energy and time as costing currencies.
2.  Energetic handling costs represented approximately 2% of corresponding gains.
3.  The tendency of profitability (gain per unit handling time) to increase with prey size was weakened by including energetic handling costs.
4.  Time was judged to be a more appropriate currency than energy for costing prey-handling behaviour.
5.  The importance of time as a costing currency, either through the principle of lost opportunity or through exposure to mortality risk, may extend to other behavioural systems, including aggression.     

Screening for cervical cancer by direct inspection.

OBJECTIVE--To assess the efficacy of visual screening for cervical cancer in the maternal and child health setting. DESIGN--Clinical and cytological screening. SETTING--Maternal and child health centres, Delhi. SUBJECTS--44,970 women attending the centres from May 1988 to March 1991. RESULTS--238 cancers in early stages (0-IIa) were detected cytologically and proved through biopsy. Prevalence of cancer in women defined as high risk through examination by speculum was 29/1000 as compared to 1.53/1000 among women with a normal looking cervix. Though only 11.4% women belonged to the high risk category, 63% had early stage cancer. If all women with bleeding symptoms were included in the high risk category, the yield of cancer would be 71.4% (170/238) by referring only 15.6% of women attending maternal and child health centres for further evaluation through cytology or colposcopy. CONCLUSION--Though visual screening is a suboptimal strategy in comparison to the cytological screening, it may be useful where there is a heavy load of prevalent cancer and where cytological screening may not be available for years to come.     

The future of cervical cancer prevention in Europe

Cervical cancer remains a significant source of disease and death in Europe. However, we now have the means to prevent virtually every case of cervical cancer through comprehensive, population-based, organised cervical cancer prevention programmes that effectively integrate cervical screening with the new technologies and vaccines that are now available. Given the potential health benefits of these programmes in reducing disease incidence and mortality, their establishment is now an ethical imperative for all European countries.     

Present challenges in cervical cancer prevention: Answers from cost-effectiveness analyses

Simulation models are commonly used to address important health policy issues that cannot be explored through experimental studies. These models are especially useful to determine a set of strategies that result in a good value for money (cost-effectiveness). Several mathematical models simulating the natural history of HPV and related diseases, especially cervical cancer, have been developed to calculate a relative effectiveness and cost-effectiveness of HPV vaccination and cervical cancer screening interventions. Virtually all cost-effectiveness analyses identify HPV vaccination programmes for preadolescent girls to be cost-effective, even for relatively low vaccination coverage rates. Routine vaccination of preadolescent girls is the primary target population for HPV vaccination as it shows to provide the greatest health impact. Cost-effectiveness analyses assessing other vaccine target groups are less conclusive. Adding additional age-cohorts would accelerate health benefits in some years, although cost-effectiveness becomes less favourable as age at vaccination increases. Including men in HPV vaccination programmes may be a less efficient strategy if done at the expense of female vaccination coverage for reducing the burden of HPV in the population. However, as the HPV vaccine price decreases, the cost-effectiveness of universal vaccination improves, becoming equally as efficient as female-only vaccination. Vaccine price is a decisive factor in the cost-effectiveness analyses. The lower the price, the greater the likelihood that vaccination groups other than the primary target would be considered cost-effective.     

Opportunities to improve the prevention and treatment of cervical cancer

Human papillomavirus (HPV) is a causal agent for approximately 5.3% of cancers worldwide, including cervical cancer, and subsets of genital and head and neck cancer. Persistent HPV infection is a necessary, but not sufficient, cause of cervical cancer. Of the >100 HPV genotypes, only about a dozen, termed "high-risk", are associated with cancer. HPV-16 is present in approximately 50% of all cervical cancers and HPV-16, HPV-18, HPV-31 and HPV-45 together account for approximately 80%. Most high-risk HPV infections are subclinical, and are cleared by the host's immune system. The remainder produces low or high-grade squamous intraepithelial lesions (SILs), also called cervical intraepithelial neoplasia (CIN), which also may regress spontaneously. However persistent high grade SIL represents the precursor lesion of cervical cancer and carcinogenic progression is associated with integration of the viral DNA, loss of E2 and upregulation of viral oncogene expression, and chromosomal rearrangements like 3q gain. Cytologic screening of the cervix for SIL and intervention has reduced the incidence of cervical cancer in the US by an estimated 80% and HPV viral DNA and other molecular tests may improve screening further. The licensure of a preventive HPV vaccine ushers in a new era, but issues remain, including: protection restricted to a few oncogenic HPV types, access in low resource settings and impact on current cytologic screening protocols. Importantly, preventive HPV vaccination does not help with current HPV infection or disease. Here we examine the potential of second-generation preventive HPV vaccines and therapeutic HPV vaccination to address these outstanding issues.     

子宫颈癌细胞学新型生物标志、诊断标志物的筛选和开发现状

子宫颈癌至今仍是全球范围内一个重要的公共卫生问题,是妇女疾病死亡的主要原因之一。因此,子宫颈癌细胞学的筛查、早期诊断和治疗越来越受到重视,虽然新的技术不断推出使子宫颈癌的早期筛查及诊治水平有了很大提高,但仍缺乏新型的特异性生物学标志物。本文从新的子宫颈癌相关蛋白生物标志物和诊断靶标的发现,治疗子宫颈癌的药物作用、治疗靶标和作用机制的评估,子宫颈癌相关微小核糖核酸作为诊断和治疗靶标的筛选等方面对子宫颈脱落细胞筛查方法的开发和研究进展进行综述,为子宫颈癌的早期筛查和诊断寻找新的生物学标志物。     

The ideal strategy for cervical cancer screening in Japan: Result from the Fukui Cervical Cancer Screening Study

Introduction

The aims of the Fukui Cervical Cancer Screening (FCCS) study are to determine the frequency of women with high‐risk HPV (hrHPV), whether HPV16 or HPV18 (HPV16/18), in the Japanese cancer screening population for the first time and to identify the best strategy for cervical cancer screening in Japan.

Methods

This study enrolled 7584 women aged ≥25 years who were undergoing routine screening. All women underwent LBC and cobas HPV tests. Women with abnormal cytology, whether hrHPV positive or negative; women with hrHPV positivity with either normal or abnormal cytology; and women randomly selected from women with normal cytology and negative hrHPV negative were referred for colposcopy.

Results

The prevalences of hrHPV positivity and HPV16/18 positivity were 6.8% and 1.7%, respectively. The baseline data from the FCCS study showed that the combination of HPV tests and cytology was more sensitive than cytology with respect to the detection of intraepithelial neoplasia grade 2 or worse. However, the specificity (94.1%) of the co‐testing strategy that required all women with abnormal cytology or hrHPV positivity to be referred for colposcopy was much lower than that (97.8%) of cytology. The sensitivity and specificity of the co‐testing strategy that required only women with abnormal cytology or HPV16/18 positivity to undergo colposcopy were 85.5% and 97.0%, respectively.

Conclusion

The baseline data from the FCCS study suggest that a cervical cancer screening strategy in which only women with abnormal cytology or HPV16/18 positivity undergo colposcopy offers a more balanced sensitivity and specificity than other strategies.