Introducing human papillomavirus (HPV) primary testing in the age of HPV vaccination: projected impact on colposcopy services in Wales.

OBJECTIVE: To determine the demand for colposcopy in the Cervical Screening Wales programme after the introduction of human papillomavirus (HPV) cervical screening, which coincided with the start of screening of women vaccinated against HPV types 16/18. DESIGN: The study used a computational model that assigns screening and screening-related colposcopy events to birth cohorts in individual calendar years. SETTING: Cervical Screening Wales. POPULATION: Women aged 25-64 years from birth cohorts 1953-2007. METHODS AND MAIN OUTCOME MEASURES: We estimated the numbers of colposcopies and high-grade cervical intraepithelial lesions (CIN2+) within Cervical Screening Wales in 2018-32, using official population projections for Wales and published estimates of the effects of HPV screening and vaccination. RESULTS: Vaccination will reduce the number of colposcopies by 10% within the first 3-4 years after the national roll-out of HPV screening, and by about 20% thereafter. The number of screening colposcopies is estimated to increase from 6100 in 2018 and peak at 8000 (+31%) in 2021, assuming current screening intervals are maintained. The numbers of CIN2+ lesions follow similar patterns, stabilising at around 1000 diagnoses per year by 2026, approximately 60% lower than at present. Extending the screening intervals to 5 years for all women shows similar trends but introduces peaks and troughs over the years. CONCLUSIONS: Vaccination will not fully prevent an increase in colposcopies and detected CIN2+ lesions during the first 2-3 years of HPV-based screening but the numbers are expected to decrease substantially after 5-6 years. TWEETABLE ABSTRACT: HPV-based cervical screening will initially increase colposcopy referral. In 6 years, this increase will be reversed, partly by HPV vaccination.

Development and validation of a haematuria cancer risk score to identify patients at risk of harbouring cancer.

BACKGROUND: A lack of consensus exists amongst national guidelines regarding who should be investigated for haematuria. Type of haematuria and age-specific thresholds are frequently used to guide referral for the investigation of haematuria. OBJECTIVES: To develop and externally validate the haematuria cancer risk score (HCRS) to improve patient selection for the investigation of haematuria. METHODS: Development cohort comprise of 3539 prospectively recruited patients recruited at 40 UK hospitals (DETECT 1; ClinicalTrials.gov: NCT02676180) and validation cohort comprise of 656 Swiss patients. All patients were aged >18 years and referred to hospital for the evaluation of visible and nonvisible haematuria. Sensitivity and specificity of the HCRS in the validation cohort were derived from a cut-off identified from the discovery cohort. RESULTS: Patient age, gender, type of haematuria and smoking history were used to develop the HCRS. HCRS validation achieves good discrimination (AUC 0.835; 95% CI: 0.789-0.880) and calibration (calibration slope = 1.215) with no significant overfitting (P = 0.151). The HCRS detected 11.4% (n = 8) more cancers which would be missed by UK National Institute for Health and Clinical Excellence guidelines. The American Urological Association guidelines would identify all cancers with a specificity of 12.6% compared to 30.5% achieved by the HCRS. All patients with upper tract cancers would have been identified. CONCLUSION: The HCRS offers good discriminatory accuracy which is superior to existing guidelines. The simplicity of the model would facilitate adoption and improve patient and physician decision-making.

Factors related to inter-observer reproducibility of conventional Pap smear cytology: a multilevel analysis of smear and laboratory characteristics.

OBJECTIVE: To identify factors that influence the inter-observer reproducibility of the routine, conventional Pap smear cytology (Pap smear test) in a network of certificated laboratories in a middle-income Latin American country. METHODS: Twenty-six laboratories provided each an average of 26 negative for malignancy (NILM) and high-grade squamous intraepithelial lesion (HSIL) Pap smears. An external panel reviewed the slides. The kappa index and multilevel logistic regression were used to estimate the reproducibility and odds ratios (OR) of a false result with 95% confidence intervals (95% CI), respectively. Results are presented for laboratories that collect (collector laboratories) and do not collect (non-collector laboratories) samples. RESULTS: The agreements ranged widely (median kappa 0.51, range 0.16-0.70). The overall false-positive (FP) and false-negative (FN) rates were 31% (95% CI 27-35) and 11% (95% CI 7-17). Among collector laboratories (N = 14), a bigger sample collection volume decreased the probability of a FP (OR-adjusted 0.05, 95% CI 0.02-0.1) whereas the number of quality defects (OR-adjusted 1.67, 95% CI 1.25-2.24), high workload (OR-adjusted 5.52, 95% CI 3.85-7.92) and collection by cytotechnologists (OR-adjusted 1.28, 95% CI 1.15-1.42) or health professionals (OR-adjusted 2.26, 95% CI 2.04-2.49) instead of nursing assistants increased it. Among non-collector laboratories (N = 9), the FP rate increased with the number of quality defects (OR-adjusted 1.86, 95% CI 1.06-3.26) but decreased if the samples were collected by health professionals instead of nursing assistants (OR-adjusted 0.37, 95%CI 0.17-0.80). No significant associations were observed for FN. CONCLUSIONS: Staff in charge of cervical sampling significantly determined the reproducibility of the Pap smear test, but this depended on whether the laboratory collects samples or read samples collected elsewhere.

Time to diagnosis of Type I or II invasive epithelial ovarian cancers: a multicentre observational study using patient questionnaire and primary care records.

OBJECTIVE: To compare time to diagnosis of the typically slow-growing Type I (low-grade serous, low-grade endometrioid, mucinous, clear cell) and the more aggressive Type II (high-grade serous, high-grade endometrioid, undifferentiated, carcinosarcoma) invasive epithelial ovarian cancer (iEOC). DESIGN: Multicentre observational study. SETTING: Ten UK gynaecological oncology centres. POPULATION: Women diagnosed with primary EOC between 2006 and 2008. METHODS: Symptom data were collected before diagnosis using patient questionnaire and primary-care records. We estimated patient interval (first symptom to presentation) using questionnaire data and diagnostic interval (presentation to diagnosis) using primary-care records. We considered the impact of first symptom, referral and stage on intervals for Type I and Type II iEOC. MAIN OUTCOME MEASURES: Patient and diagnostic intervals. RESULTS: In all, 78% of 60 Type I and 21% of 134 Type II iEOC were early-stage. Intervals were comparable and independent of stage [e.g. median patient interval for Type I: early-stage 0.3 months (interquartile range 0.3-3.0) versus late-stage 0.3 months (interquartile range 0.3-4.5), P = 0.8]. Twenty-seven percent of women with Type I and Type II had diagnostic intervals of at least 9 months. First symptom (questionnaire) was also similar, except for the infrequent abnormal bleeding (Type I 15% versus Type II 4%, P = 0.01). More women with Type I disease (57% versus 41%, P = 0.04) had been referred for suspected gynaecological cancer. Median time from referral to diagnosis was 1.4 months for women with iEOC referred via a 2-week cancer referral to any specialty compared with 2.6 months (interquartile range 2.0-3.7) for women who were referred routinely to gynaecology. CONCLUSION: Overall, shorter diagnostic delays were seen when a cancer was suspected, even if the primary tumour site was not recognised to be ovarian. Despite differences in carcinogenesis and stage for Type I and Type II iEOC, time to diagnosis and symptoms were similar. Referral patterns were different, implying subtle symptom differences. If symptom-based interventions are to impact on ovarian cancer survival, it is likely to be through reduced volume rather than stage-shift. Further research on histological subtypes is needed. TWEETABLE ABSTRACT: No difference in time to diagnosis for Type I versus Type II invasive epithelial ovarian cancers.

Evaluating cytology for the detection of invasive cervical cancer.

OBJECTIVE: To assess the sensitivity, the number needed to screen (NNS) and the positive predictive value (PPV) of cervical cytology for the diagnosis of cancer by age in a screening population. METHODS: A retrospective cohort of women with invasive cervical cancer nested within a census of cervical cytology. All (c. 8 million) women aged 20-64 years with cervical cytology (excluding tests after an earlier abnormality). From April 2007 to March 2010, 3372 women had cervical cancer diagnosed within 12 months of such cytology in England. The sensitivity of cervical cytology to cancer, NNS to detect one cancer and predictive values of cytology were calculated for various 'referral' thresholds. These were calculated for ages 20-24, 25-34, 35-49 and 50-64 years. RESULTS: The sensitivity of at least moderate dyskaryosis [equivalent to a high-grade squamous intraepithelial lesion (HSIL) or worse] for cancer of 89.4% [95% confidence interval (CI) 88.3-90.4%] in women offered screening was independent of age. At all ages, women with borderline-early recall or mild dyskaryosis on cytology (equivalent to ASC-US and LSIL, respectively, in the Bethesda system) had a similar risk of cervical cancer to the risk in all women tested. The PPV of severe dyskaryosis/?invasive and ?glandular neoplasia cytology (equivalent to squamous cell carcinoma and adenocarcinoma/adenocarcinoma in situ, respectively, in the Bethesda System) were 34% and 12%, respectively; the PPV of severe dyskaryosis (HSIL: severe dysplasia) was 4%. The NNS was lowest when the incidence of cervical cancer was highest, at ages 25-39 years, but the proportion of those with abnormal cytology who have cancer was also lowest in younger women. CONCLUSIONS: The PPV of at least severe dyskaryosis (HSIL: severe dysplasia) for cancer was 4-10% of women aged 25-64 years, justifying a 2-week referral to colposcopy and demonstrating the importance of failsafe monitoring for such patients. The sensitivity of cytology for cervical cancer was excellent across all age groups.

Trends in the lifetime risk of developing cancer in Great Britain: comparison of risk for those born from 1930 to 1960.

BACKGROUND: Typically, lifetime risk is calculated by the period method using current risks at different ages. Here, we estimate the probability of being diagnosed with cancer for individuals born in a given year, by estimating future risks as the cohort ages. METHODS: We estimated the lifetime risk of cancer in Britain separately for men and women born in each year from 1930 to 1960. We projected rates of all cancers (excluding non-melanoma skin cancer) and of all cancer deaths forwards using a flexible age-period-cohort model and backwards using age-specific extrapolation. The sensitivity of the estimated lifetime risk to the method of projection was explored. RESULTS: The lifetime risk of cancer increased from 38.5% for men born in 1930 to 53.5% for men born in 1960. For women it increased from 36.7 to 47.5%. Results are robust to different models for projections of cancer rates. CONCLUSIONS: The lifetime risk of cancer for people born since 1960 is >50%. Over half of people who are currently adults under the age of 65 years will be diagnosed with cancer at some point in their lifetime.

Do prostate cancer risk models improve the predictive accuracy of PSA screening? A meta-analysis.

BACKGROUND: Despite the extensive development of risk prediction models to aid patient decision-making on prostate screening, it is unknown whether these models could improve predictive accuracy of PSA testing to detect prostate cancer (PCa). The objective of this study was to perform a systematic review to identify PCa risk models and to assess the model's performance to predict PCa by conducting a meta-analysis. DESIGN: A systematic literature search of Medline was conducted to identify PCa predictive risk models that used at least two variables, of which one of the variables was prostate-specific antigen (PSA) level. Model performance (discrimination and calibration) was assessed. Prediction models validated in ≥5 study populations and reported area under the curve (AUC) for prediction of any or clinically significant PCa were eligible for meta-analysis. Summary AUC and 95% CIs were calculated using a random-effects model. RESULTS: The systematic review identified 127 unique PCa prediction models; however, only six models met study criteria for meta-analysis for predicting any PCa: Prostataclass, Finne, Karakiewcz, Prostate Cancer Prevention Trial (PCPT), Chun, and the European Randomized Study of Screening for Prostate Cancer Risk Calculator 3 (ERSPC RC3). Summary AUC estimates show that PCPT does not differ from PSA testing (0.66) despite performing better in studies validating both PSA and PCPT. Predictive accuracy to discriminate PCa increases with Finne (AUC = 0.74), Karakiewcz (AUC = 0.74), Chun (AUC = 0.76) and ERSPC RC3 and Prostataclass have the highest discriminative value (AUC = 0.79), which is equivalent to doubling the sensitivity of PSA testing (44% versus 21%) without loss of specificity. The discriminative accuracy of PCPT to detect clinically significant PCa was AUC = 0.71. Calibration measures of the models were poorly reported. CONCLUSIONS: Risk prediction models improve the predictive accuracy of PSA testing to detect PCa. Future developments in the use of PCa risk models should evaluate its clinical effectiveness in practice.

A prospective double-blind cross-sectional study of the accuracy of the use of dry vaginal tampons for self-sampling of human papillomaviruses.

OBJECTIVE: To evaluate if a dry vaginal tampon can be used to accurately detect high-risk human papillomaviruses (HPV) and so be used as a cervical screening tool for the early detection of high-grade cervical intraepithelial neoplasia (CIN2+). DESIGN: Prospective double-blinded cross-sectional study. SETTING: Colposcopy unit in North London. POPULATION: Women referred for colposcopy with both abnormal and normal cervical cytology were invited to participate in this study. METHODS: Women inserted a dry tampon in the vagina before colposcopic examination. Polymerase chain reaction (PCR) HPV test was carried out on the dry tampon. Cervical samples were collected by the colposcopist for HPV testing using Hybrid Capture (an HC2 kit). MAIN OUTCOME MEASURE: Detection of CIN2+. RESULTS: In all, 501 women participated in the study. The majority of participants (69%) were in the 25-35-year age group. Overall sensitivity and specificity for detection of CIN2+ by vaginal tampon were 76% (95% confidence interval [95% CI] 65-85) and 61% (95% CI 56-66), respectively, and HC2 had a sensitivity of 92% (95% CI 83-97) with a specificity of only 46% (95% CI 41-51). Sensitivity ratio was 0.83 (95% CI 0.73-0.94) (P = 0.004) and Specificity ratio for CIN2+ was 1.33 (95% CI 1.22-1.45). Indicating that the tampon test was significantly (P < 0.0001) more specific. Sensitivity decreased and specificity improved with increasing age. CONCLUSIONS: Dry tampon test showed reasonably high sensitivity and specificity when detecting CIN2+. The majority of participants (98%) approved of the use of dry tampons as a method of sample collection, which could be an effective alternative method for detecting HPV infection.

Is the increased risk of preterm birth following excision for cervical intraepithelial neoplasia restricted to the first birth post treatment?

OBJECTIVE: To explore whether the increased risk of preterm birth following treatment for cervical disease is limited to the first birth following colposcopy. DESIGN: Nested case-control study. SETTING: Twelve NHS hospitals in England. POPULATION: All nonmultiple births from women selected as cases or controls from a cohort of women with both colposcopy and a hospital birth. Cases had a preterm (20-36 weeks of gestation) birth. Controls had a term birth (38-42 weeks) and no preterm. METHODS: Obstetric, colposcopy and pathology details were obtained. MAIN OUTCOME MEASURES: Adjusted odds ratio of preterm birth in first and second or subsequent births following treatment for cervical disease. RESULTS: A total of 2798 births (1021 preterm) from 2001 women were included in the analysis. The risk of preterm birth increased with increasing depth of treatment among first births post treatment [trend per category increase in depth, categories <10 mm, 10-14 mm, 15-19 mm, ≥20 mm: odds ratio (OR) 1.23, 95% confidence interval (95% CI) 1.12-1.36, P < 0.001] and among second and subsequent births post treatment (trend OR 1.34, 95% CI 1.15-1.56, P < 0.001). No trend was observed among births before colposcopy (OR 0.98, 95% CI 0.83-1.16, P = 0.855). The absolute risk of a preterm birth following deep treatments (≥15 mm) was 6.5% among births before colposcopy, 18.9% among first births and 17.2% among second and subsequent births post treatment. Risk of preterm birth (once depth was accounted for) did not differ when comparing first births post colposcopy with second and subsequent births post colposcopy (adjusted OR 1.15, 95% CI 0.89-1.49). CONCLUSIONS: The increased risk of preterm birth following treatment for cervical disease is not restricted to the first birth post colposcopy; it remains for second and subsequent births. These results suggest that once a woman has a deep treatment she remains at higher risk of a preterm birth throughout her reproductive life.

How many preterm births in England are due to excision of the cervical transformation zone? Nested case control study.

BACKGROUND: Preterm births (as a proportion of all births) have been increasing in many countries. There is growing evidence of increased risk of preterm birth following excisional treatment of the cervix. We estimate the number of preterm births attributable to excisional treatments with a length of 10 mm or more in England. METHODS: Case-control study nested in a record linkage cohort of women with a histological sample at 13 hospitals in England. We combined observed age at first excisional treatment in our cohort with the weighted distribution of excision length from the case-control study to estimate the length distribution by age at first treatment among the cohort. The number of births after excision for each 5-year age group was estimated using national fertility data; published absolute risks of preterm (<37 gestational weeks) and very preterm birth (<32 weeks) were applied to these to estimate the number of preterm births per 100 women treated. Excess preterm births were estimated assuming all treatments were small. The attributable risk of preterm birth following excisional treatment in England was estimated. RESULTS: The majority of first excisional treatments at colposcopy were small (47.5%) or medium (39.1%), 9.5% were large and 4.1% were very large excisions. 4.0% of women treated before birth had more than one excisional treatment. Thus based on our cohort of 10,711 treated women and the length of treatment observed in the case control study we estimate an excess of 240 preterm births (including 57 very preterm) or 2.2 (including 0.5 very preterm) per 100 women treated. At a population level (for England) we estimate that 39,101 women aged 20-39 would be treated each year and that these treatments will lead to an excess of 840 preterm births (including 196 very preterm) in England each year. CONCLUSIONS: Assuming associations between preterm birth and treatment for cervical disease are causal; we estimate that an excess 840 (2.5%) preterm birth in England each year are due to excisional treatments of 10 mm or more. Those that go on to become pregnant should be closely monitored during antenatal period to reduce their risk of preterm birth.

Benefits and harms of cervical screening from age 20 years compared with screening from age 25 years.

BACKGROUND: To quantify the benefits (cancer prevention and down-staging) and harms (recall and excess treatment) of cervical screening starting from age 20 years rather than from age 25 years. METHODS: We use routine screening and cancer incidence statistics from Wales (for screening from age 20 years) and England (screening from 25 years), and unpublished data from the National Audit of Invasive Cervical Cancer to estimate the number of: screening tests, women with abnormal results, referrals to colposcopy, women treated, and diagnoses of micro-invasive (stage 1A) and frank-invasive (stage IB+) cervical cancers (under three different scenarios) in women invited for screening from age 20 years and from 25 years. RESULTS: Inviting 100,000 women from age 20 years yields an additional: 119,000 screens, 20,000 non-negative results, 8000 colposcopy referrals, and an extra 3000 women treated when compared with inviting from age 25 years. Screening from age 20 years prevents between three and nine frank invasive cancers and between 0 and 23 cancers in total (depending on the scenario). A cumulative increase of nine stage IB+ cancers corresponds to an annual rate increase of 0.9 per 100,000 women aged 20-29 years. CONCLUSIONS: To prevent one frank invasive cancer, one would need to do between 12,500 and 40,000 additional screening tests in the age group 20-24 years and treat between 300 and 900 women.

Characteristics and screening history of women diagnosed with cervical cancer aged 20-29 years.

BACKGROUND: There was concern that failure to screen women aged 20-24 years would increase the number of cancers or advanced cancers in women aged 20-29 years. We describe the characteristics of women diagnosed with cervical cancer in England aged 20-29 years and examine the association between the period of diagnosis, screening history and FIGO stage. METHODS: We used data on 1800 women diagnosed with cervical cancer between April 2007 and March 2012 at age 20-29 from the National Audit of Invasive Cervical Cancers. RESULTS: The majority of cancers (995, or 62% of those with known stage) were stage 1A. Cancer at age 20-24 years was rare (12% of those aged 20-29 years), when compared with age 25 (24%) and age 26-29 years (63%); however, cancers in women aged 20-24 years tended to be more advanced and were more often of a rare histological type. For 59% of women under age 30, the cervical cancer was screen detected, most of them (61%) as a result of their first screening test. A three-fold increase in the number of cancers diagnosed at age 25 years was seen since the start of the study period. CONCLUSION: Cervical cancer at age 20-24 years is rare. Most cancers in women under age 30 years are screen detected as microinvasive cancer.

A surveillance model for skin cancer in organ transplant recipients: a 22-year prospective study in an ethnically diverse population.

Skin cancer is a frequent complication of organ transplantation. Current guidelines advise specialist skin surveillance but there are limited data on how these should be implemented. This study determines overall burden of cancer and relevant intervals for strategic surveillance in an ethnically diverse transplant population. Prospective data on time to first and subsequent cancers and cumulative burden with respect to defined risk factors were analyzed in a cohort of 1010 patients in a UK center over 22 years. Among 931 individuals transplanted >6 months (mean 10.3 years), 1820 skin cancers occurred in 267 (29%) individuals and were multiple in 66%. Cumulative incidence at 5, 10, 20 and 30 years was 11%, 25%, 54% and 74%, with median time to second, third and fourth cancers of 24, 14.7 and 8.4 months, respectively. Tumors were overwhelmingly squamous and basal cell carcinomas (73% and 24%, respectively). Skin phototype, ultraviolet radiation exposure, age at transplant and duration of transplant were significant risk predictors and were used to construct clinically relevant surveillance intervals. This study provides a comprehensive, prospective analysis of skin cancer morbidity and risk in an ethnically diverse transplant population from which we derive an evidence-based skin cancer surveillance program.

Characteristics of HPV infection over time in European women who are HIV-1 positive.

OBJECTIVE: The objectives of the study were to investigate high-risk human papillomavirus (HR-HPV) infection and type distribution in women infected with HIV-1, and to determine the relevance of HR-HPV positivity and persistence/loss to the development of high-grade cervical disease. DESIGN: A total of 518 European women infected with HIV attending for routine gynaecological care consented to 6-monthly follow-up visits over 3 years, with surveillance of cytology, colposcopy and histopathology, where relevant, and longer follow-up, where possible. SETTING: European women infected with HIV attending for routine gynaecological care. POPULATION OR SAMPLE: 518 European women infected with HIV attending for gynaecological care in 6 hospital-based European centres - Dublin, Edinburgh, London, Milan, Paris, and Warsaw. METHODS: Cervical screening was achieved by liquid-based cytology (LBC) of brush samples in PreservCyt® medium. The HPV testing of residual samples was performed by Hybrid-Capture II, with genotyping of positives using the HPV Line Blot Assay. Histology results were accessed where available. MAIN OUTCOME MEASURES: Description of high risk human papillomavirus (HR-HPV) infection and type distribution in HIV-1 infected women. RESULTS: The estimated prevalence at baseline of any HR-HPV type was 49.5% (46.3-52.8%): 10.2% for HPV 16 and 4.3% for HPV 18. The prevalence increased with increasing immunosuppression. Multiple infections were detected in 26.8%. HR-HPV genotypes were detected in 34.9% of cases with normal cytology, in 77.2% of cases with atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion (ASCUS/LSIL) and in 90.8% of cases with high-grade SIL (HSIL). The prevalence of HPV 16 in HSIL was 38.5%, with the three most common types thereafter having prevalence rates of 19.2% (HPV 58), 19.2% (HPV 53) and 16.6% (HPV 52). The overall persistence of any high-risk type was 55.8%. We found that 6 months persistence of HPV 16 occurred in 24 women. Seven cases of high-grade cervical disease developed, and all were associated with initial/persistent HR-HPV positivity. CONCLUSIONS: A wide diversity of HPV types was evident, and multiple infections were common. Detection or persistence of any HR-HPV was associated with a very low incidence of subsequent high-grade disease.

Effect of diindolylmethane supplementation on low-grade cervical cytological abnormalities: double-blind, randomised, controlled trial.

BACKGROUND: Cervical screening identifies many women with low-grade abnormalities. In vitro and in vivo studies have shown that diindolylmethane (DIM) could potentially halt (cervical) carcinogenesis. We report on a randomised controlled trial of the effect of DIM in women with low-grade cervical cytological abnormalities. METHODS: We conducted a pragmatic double-blind, randomised controlled trial of 150 mg DIM (from BioResponse DIM) or placebo daily for 6 months in women with newly diagnosed, low-grade cytological abnormalities. Randomisation was in the ratio 2 (DIM) to 1 (placebo). All women were invited for colposcopy at 6 months with biopsy of any abnormality. RESULTS: Of the 551 randomised women available for analysis, 9% on DIM and 12% on placebo had cervical intraepithelial neoplasia-2 (CIN2) or worse after 6-month supplementation (risk ratio (RR) 0.7 (95% confidence interval (CI): 0.4-1.2)), whereas 4.6% and 5.1%, respectively, had CIN3 or worse (RR 0.9 (95% CI: 0.4-2.0)). A total of 27.3% of women on DIM and 34.3% on placebo had no sign of disease (negative cytology, colposcopy and human papilloma virus (HPV) tests) at 6 months (RR 0.8 (95% CI: 0.6-1.0)). Of those HPV-positive at baseline, 69% (114 out of 166) of the DIM group were positive at 6 months compared with 61% (43 out of 71) of the placebo group: RR 1.1 (95% CI: 0.9-1.4). Diindolylmethane supplementation was well tolerated. CONCLUSION: The results suggest that short-term DIM supplementation (150 mg day(-1)) is well tolerated, but is unlikely to have an effect on cytology or HPV infection. Uncertainty remains regarding its effect on CIN2+.

Are women ready for the new cervical screening protocol in England? A systematic review and qualitative synthesis of views about human papillomavirus testing.

BACKGROUND: A new protocol for human papillomavirus (HPV) testing within the UK cervical screening programme commenced in April 2011, creating new patient experiences. This is the first review to synthesise a substantial body of international evidence of women's information needs, views and preferences regarding HPV testing. We aimed to inform the development of educational materials to promote informed choice, reduce anxiety and improve disease control. METHODS: We searched 12 bibliographic databases. Two reviewers independently screened papers and assessed study quality; disagreements were resolved by discussion. Results were extracted verbatim and authors' findings treated as primary data. Studies were synthesised collaboratively using framework methods. RESULTS: We synthesised findings from 17 studies. Women had overwhelmingly negative concerns; an HPV diagnosis was daunting, had associated problems of disclosure of a sexually transmitted infection (STI), impacted on relationships and provoked fear of stigmatisation. Nevertheless, many thought HPV testing could be a preferable alternative to repeat cytology. Knowledge was poor; women struggled to interpret limited information in the context of existing knowledge about STIs and cervical cancer. CONCLUSION: Women are likely to be poorly informed, have limited understanding and many unanswered questions. This could increase anxiety and reduce ability to make informed choices, presenting a substantial challenge for those who design and provide information.

Cervical cancer incidence in young women: a historical and geographic controlled UK regional population study.

BACKGROUND: The commencing age of cervical screening in England was raised from 20 to 25 years in 2004. Cervical cancer incidence in young women of England is increasing. It is not clear if this is due to either greater exposure to population risk factors or reduced cervical screening. METHODS: We measured if the relative risk of cervical cancer in younger women (20-29 years) of the north-east of England (NE) differed to that of women aged 30yrs and above since 2004. We also measured average annual percentage change (AAPC) in the 3 yr moving average incidence for all age-groups. Regional screening coverage rate and population risk factors were reviewed. Comparisons were made with Wales where screening continues to commence from the age of 20yrs. RESULTS: Cervical cancer incidence in women aged 20-29 increased annually by an average of 10.3% between 2000 and 2009. The rise in women aged 30-39 was less steep (3.5%/year) but no significant rise was observed in women aged 40-49. Socioeconomic factors remained stable or improved during the time period except for the incidence of chlamydia, herpes simplex and in particular, genital warts, which increased significantly in young women. Data from Wales show similar results. CONCLUSION: The incidence of cervical cancers in young women of the NE is increasing. The rise in incidence is unrelated to the change in screening policy in 2004. Close monitoring of incidence in young women and a greater attempt to reverse the current decline in screening coverage of women aged 25-29 years are recommended.

Review of cytology and histopathology as part of the NHS Cervical Screening Programme audit of invasive cervical cancers.

OBJECTIVE: To audit pathology slide reporting in the Cervical Screening Programme in England by reviewing cytology and histology slides from women subsequently diagnosed with invasive cervical cancer. METHODS: Between April 2007 and March 2010, 6113 women diagnosed with cervical cancer were identified. Cervical cytology and histology slides taken within 10 years of diagnosis were identified and where possible reviewed after a nationally agreed protocol. Reviewers were not blinded to the original reading of each sample. Most cytology samples before 2005 were conventional, most after 2007 liquid based. RESULTS: Of 13,745 cytology results from women developing cervical cancer, 55% were reviewed. The review result was identical for 55% of slides. Of 3759 originally normal slides, only 45% were normal on review: 11% were inadequate, 21% low grade (borderline or mild dyskaryosis) and 23% high grade (moderate dyskaryosis or worse). Of tests originally normal taken over 5.5 years before diagnosis, 14% were upgraded to high grade compared with 37% within 3.5 years of diagnosis. Of 5159 histology specimens recorded within 10 years of diagnosis of a cancer, 3895 were reviewed. Overall, 94% of samples reviewed retained the original diagnosis. One per cent (33/3012) of cancers were downgraded and 5% (6/112) of negative samples were upgraded to cancer upon review (four of which were taken within 2 months of diagnosis). In comparison, 15% (14/91) of cervical glandular intraepithelial neoplasia (CGIN) and 12% (38/314) of cervical intraepithelial neoplasia grade 3 (CIN3) were upgraded to cancer. CONCLUSIONS: In spite of the excellent quality of cytology in England, a high proportion of negative cytology taken up to three and a half years before diagnosis were considered to contain abnormal cells by reviewers informed of the subsequent cancer. Continuing these reviews, with a strong focus on education, will ensure a clear understanding of these slides and further reduce the risk of developing cervical cancer.

The impact of offering multiple cervical screening options to women whose screening was overdue in Dumfries and Galloway, Scotland.

Most women who develop cancer have not been screened regularly. One in four women in Scotland, is overdue for cervical screening. Aim was to assess the impact of offering multiple cervical screening options to women whose screening is overdue. A prospective cohort study including all women whose screening was overdue, aged 30-60 years in Dumfries and Galloway in 2012. Potentially eligible women (n = 4146) were identified split into six groups. Women aged 30-55 years were allocated to three different groups. Group 1 (letter, n = 1246), Group 2 (letter and kit, n = 221), Group 3 (letter, n = 2031). Women aged 56-60 years were allocated to: Group 4 (letter, n = 292), Group 5 (letter and kit, n = 292) and Group 6 (control, n = 64). Women who self-collected a vaginal sample were requested to complete a questionnaire. The percentages of women responding were 24 % (21-26), 32 % (25-38), 16 % (14-18), 15 % (11-20) and 12 % (9-17) in groups 1 to 5 respectively, compared with 3 % (0-11) among controls. A significantly higher number of women (n = 383, 10 % of 3815) opted for self-sampling in comparison with undergoing a cervical screening test (CST) at the GP practice (n = 197, 5 %, x2 = 59.0, p < 0.0001). The Evalyn® Brush was well accepted (218/313 = 70 %) by those who requested self-sampling. Almost all (265/272 = 97 %) women who self-collected a vaginal sample said that if they had the option of self-sampling, they would regularly participate in future cervical screening. Offering more flexible screening options, self-sampling in particular, appears to increase cervical screening participation.

Cancer incidence in the United Kingdom: projections to the year 2030.

BACKGROUND: Projections of cancer incidence are important for planning health services and to provide a baseline for assessing the impact of public health interventions. METHODS: Rates estimated from smooth function age-period-cohort modelling of cancer incidence data from Great Britain 1975 to 2007 are extrapolated to 2030 and applied to UK population projections. Prostate and breast cancer projections take into account the effect of screening. RESULTS: Overall rates of cancer are projected to be stable over the next 20 years, but this masks individual changes. In both sexes, age-standardised rates of cancers of the stomach, larynx, bladder and leukaemia are projected to fall by ≥1% per year, whereas cancers of the lip, mouth and pharynx (ICD-10 C00-C14) and melanoma are projected to increase by ≥1% per year. The growing and aging populations will have a substantial impact: numbers of cancers in men and women are projected to increase by 55% (from 149,169 to 231,026) and 35% (from 148,716 to 200,929), respectively, between 2007 and 2030. The model used yields similar results to those of Nordpred, but is more flexible. CONCLUSION: Without new initiatives for smoking and obesity reduction, the number of cancers in the United Kingdom will increase substantially reflecting the growing and aging populations.