Estimating the efficacy of screening by auditing smear histories of women with and without cervical cancer. The National Co-ordinating Network for Cervical Screening Working Group.

The screening histories of all 348 women with invasive cervical cancer diagnosed in 1992 in 24 self-selected district health authorities and health boards in England, Wales and Scotland were compared with those of 677 age- and residency-matched controls. The controls were randomly selected from the family health services authority (FHSA) register. Screening histories, comprising the dates and results of all smears taken before the date of diagnosis of the patient''s cancer, were determined from the FHSA computer and laboratory records. We estimate that the number of cases of cervical cancer in participating districts in 1992 would have been 57% (95% confidence interval 28-86%) greater if there had been no previous screening. In women under the age of 70 it would have been approximately 75% (31-115%) greater. Extrapolation of the results from this pilot suggests that screening prevented between 1100 and 3900 cases of invasive cervical cancer in the UK in 1992. Women with stage 1B cancer or worse were more likely to have no record of previous screening than controls: 47% of these women under the age of 70 had been adequately screened according to current (5 yearly screening) guidelines, compared with 75% of matched controls. Thirteen per cent of all patients under age 70 had screening histories indicative of inadequate follow-up of smears requiring colposcopy. The proportion of microinvasive cases with screening predating diagnosis was similar to the proportion of controls. There was a strong correlation between stage and age: 56% of cancers in women under 35 were microinvasive compared with just 9% in women 65 years or over. The ''relative protection'' following a negative smear was greatest in the first 12 months and fell off towards the end of the fifth year. These data suggest that full adherence to current guidelines could perhaps have prevented another 1250 cases, but additional steps would have been required to prevent some of the 2300 remaining cases in women under the age of 70.     

Standardized lifetime risk

The authors propose the use of two new standardized measures of risk, the standardized lifetime risk and the standardized number of years of life lost. These measures maintain the advantages of standardized rates but are more readily understood without special training. In this paper, standardizing weights based on 1992 data from England and Wales are provided, and the new measures are illustrated with a variety of examples. The new standardized rates are useful for examining trends over time; for comparing the impact of various diseases on public health; and for comparing rates of a given disease in several different countries. The authors think it is far more informative to say that 41 out of every 1,000 women die of breast cancer than to say that the standardized mortality rate is 51 per 100,000 women per year.     

Refining the Amsterdam Criteria and Bethesda Guidelines: testing algorithms for the prediction of mismatch repair mutation status in the familial cancer clinic.

PURPOSE: Hereditary nonpolyposis colon cancer (HNPCC) is a Mendelian dominant syndrome of bowel, endometrial, and other cancers and results from germline mutations in mismatch repair (MMR) genes. HNPCC is now best diagnosed on molecular grounds using MMR mutation screening, aided by microsatellite instability (MSI) and immunohistochemistry in tumors. Selection of families for molecular investigation of HNPCC is usually based on suboptimal methods (Amsterdam Criteria or Bethesda Guidelines), but these can be improved using additional clinical data (mean ages of affected persons and presence of endometrial cancer) in a quantitative model. METHODS: We have verified the performance of the Wijnen model and have shown that it remains valid when HNPCC is diagnosed using mutation screening, MSI, and immunohistochemistry. We have also set up and verified our own models (Amsterdam-plus and Alternative), which perform at least as well as the Wijnen model. RESULTS: The Amsterdam-plus model improves on the Amsterdam Criteria by using five extra variables (numbers of colorectal and endometrial cancers in the family, number of patients with five or more adenomas, number with more than one primary cancer of the colorectum or endometrium, and mean age of presentation) and performs better than the Wijnen model. The Alternative model avoids the need to evaluate the Amsterdam Criteria and performs nearly as well as the other models. CONCLUSION: We believe that a quantitative model, such as the Amsterdam-plus model, should be the first choice for selecting families or patients for evaluation of HNPCC using molecular tests. We present an algorithm for this process.     

Evaluation of the UK breast screening programmes

National breast screening programmes were set up in the UK inthe early 1990s. Although they are quality-assured and publishprocess measures of performance, there is a lack of data linkingthe screening process to breast cancer mortality. A new analysisof trends in England and Wales suggests that the effect of screeninghas been to reduce mortality by 8% over 10 years in those eligiblefor screening in 1990.     

Risk of cutaneous melanoma in relation to the numbers, types and sites of naevi: a case-control study.

The atypical mole syndrome (AMS) phenotype, characterised by a large number of common naevi as well as atypical naevi, has been described in families with a genetic susceptibility to melanoma. However, the importance of this phenotype for melanoma in the general population has not been conclusively determined. This study was designed to examine the types and distribution of naevi as well as the prevalence of the AMS phenotype in melanoma patients in England compared with controls. A total of 426 cutaneous melanoma cases (61% of all incident cases) aged 16-75 years were recruited between 1989 and 1993 from the north-east Thames region of the UK and 416 controls from the same age group were recruited over the same period and from the same region. Each subject answered a questionnaire covering demographic details, sun exposure history and other risk factors and underwent a skin examination with total body naevus count performed by a dermatologist. The AMS phenotype was defined using a scoring system. Atypical naevi gave the highest relative risk for cutaneous melanoma, with an odds ratio (OR) of 28.7 (P < 0.0001) for four or more atypical naevi compared with none. Many common naevi were also an important risk factor: the OR for 100 or more naevi 2 mm or above in diameter compared with 0-4 naevi was 7.7 (P < 0.0001). Melanoma was also associated with naevi on sun-exposed sites but also with naevi on non-sun-exposed sites such as the dorsum of the feet, buttocks and anterior scalp. Sixteen per cent of the cases had the AMS phenotype compared with 2% of the controls (OR 10.4, P < 0.0001). The AMS phenotype was more common in males than females (P = 0.008). The odds ratio for the presence of the AMS phenotype was dependent on age, with an odds ratio of 16.1 (95% CI 4.6-57.5) for the presence of the AMS phenotype if aged less than 40 compared with an odds ratio of 6.9 (95% CI 2.9-16.6) if aged 40 or more. The AMS phenotype was strongly predictive of an increased risk of melanoma outside the familial context.     

Benefit of cervical screening at different ages: evidence from the UK audit of screening histories

While most experts agree that cervical screening is effective, there remains controversy over the most appropriate screening interval. Annual screening is common in North America. In England, some argue for 3-yearly screening while others believe 5-yearly screening is adequate, and the frequency varies from one part of the country to another. Screening histories of 1305 women aged 20-69 years, diagnosed with frankly invasive cervical cancer and 2532 age-matched controls were obtained from UK screening programme databases. Data were analysed in terms of time since last negative, and time since last screening smear. Five-yearly screening offers considerable protection (83%) against cancer at ages 55-69 years and even annual screening offers only modest additional protection (87%). Three-yearly screening offers additional protection (84%) over 5-yearly screening (73%) for cancers at ages 40-54 years, but is almost as good as annual screening (88%). In women aged 20-39 years, even annual screening is not as effective (76%) as 3-yearly screening in older women, and 3 years after screening cancer rates return to those in unscreened women. This calls into question the policy of having a uniform screening interval from age 20 to 64 years and stresses the value of screening in middle-aged women.British Journal of Cancer (2003) 89, 88-93. doi:10.1038/sj.bjc.6600974 www.bjcancer.com     

Antibodies to heat-shock protein 27 are associated with improved survival in patients with breast cancer.

The overexpression of the heat-shock proteins hsp90, hsp70 and hsp27 in human mammary carcinomas has previously been shown to correlate with reduced overall survival. Moreover, antibodies to hsp90 were detectable in the serum of a large proportion of breast cancer patients but they were not found in normal controls. High antibody levels also correlated with reduced survival. Here, we show that antibodies to hsp27 were also detectable in the sera from breast cancer patients but not from normal controls, whereas antibodies to hsp70 were detectable in approximately one-third of both groups. The presence of antibodies to hsp27 was correlated with an improved rather than a reduced survival, particularly beyond the first 5 years. Hence, the overexpression of hsps in breast cancer cells does not provoke a generalized immune response to all the hsps. Moreover, the presence of antibodies to different hsps has distinct associations with survival. These effects are discussed in terms of the mechanisms that provoke an immune response to the hsps and the protective/non-protective effects of such a response.