What cervical screening is appropriate for women who have been vaccinated against high risk HPV? A simulation study.

Women vaccinated against HPV16/18 are approaching the age for cervical screening; however, an updated screening algorithm has not been agreed. We use a microsimulation model calibrated to real published data to determine the appropriate screening intensity for vaccinated women. Natural histories in the absence of vaccination were simulated for 300,000 women using 10,000 sets of transition probabilities. Vaccination with (i) 100% efficacy against HPV16/18, (ii) 15% cross-protection, (iii) 22% cross-protection, (iv) waning vaccine efficacy and (v) 100% efficacy against HPV16/18/31/33/45/52/58 was added, as were a range of screening scenarios appropriate to the UK. To benchmark cost-benefits of screening for vaccinated women, we evaluated the proportion of cancers prevented per additional screen (incremental benefit) of current cytology and likely HPV screening scenarios in unvaccinated women. Slightly more cancers are prevented through vaccination with no screening (70.3%, 95% CR: 65.1-75.5) than realistic compliance to the current UK screening programme in the absence of vaccination (64.3%, 95% CR: 61.3-66.8). In unvaccinated women, when switching to HPV primary testing, there is no loss in effectiveness when doubling the screening interval. Benchmarking supports screening scenarios with incremental benefits of ≥2.0%, and rejects scenarios with incremental benefits ≤0.9%. In HPV16/18-vaccinated women, the incremental benefit of offering a third lifetime screen was at most 3.3% (95% CR: 2.2-4.5), with an incremental benefit of 1.3% (-0.3-2.8) for a fourth screen. For HPV16/18/31/33/45/52/58-vaccinated women, two lifetime screens are supported. It is important to know women's vaccination status; in these simulations, HPV16/18-vaccinated women require three lifetime screens, HPV16/18/31/33/45/52/58-vaccinated women require two lifetime screens, yet unvaccinated women require seven lifetime screens.

Near-critical SIR epidemic on a random graph with given degrees.

Emergence of new diseases and elimination of existing diseases is a key public health issue. In mathematical models of epidemics, such phenomena involve the process of infections and recoveries passing through a critical threshold where the basic reproductive ratio is 1. In this paper, we study near-critical behaviour in the context of a susceptible-infective-recovered epidemic on a random (multi)graph on n vertices with a given degree sequence. We concentrate on the regime just above the threshold for the emergence of a large epidemic, where the basic reproductive ratio is [Formula: see text], with [Formula: see text] tending to infinity slowly as the population size, n, tends to infinity. We determine the probability that a large epidemic occurs, and the size of a large epidemic. Our results require basic regularity conditions on the degree sequences, and the assumption that the third moment of the degree of a random susceptible vertex stays uniformly bounded as [Formula: see text]. As a corollary, we determine the probability and size of a large near-critical epidemic on a standard binomial random graph in the 'sparse' regime, where the average degree is constant. As a further consequence of our method, we obtain an improved result on the size of the giant component in a random graph with given degrees just above the critical window, proving a conjecture by Janson and Luczak.

Black-white differences in cancer risk in Harare, Zimbabwe, during 1991-2010.

Data from 20 years of cancer registration in Harare (Zimbabwe) are used to investigate the risk of cancer in the white population of the city (of European origin), relative to that in blacks (of African origin). In the absence of information on the respective populations-at-risk, we calculated odds of each major cancer among all cancers, and took the odds ratios of whites to blacks. Some major differences reflect obvious phenotypic differences (the very high incidence of skin cancer-melanoma and nonmelanoma--in the white population), whereas others (high rates of liver cancer, Kaposi sarcoma and conjunctival cancers in blacks) are the result of differences in exposure to infectious agents. Of particular interest are cancers related to lifestyle factors, and how the differences in risk are changing over time, as a result of evolving lifestyles. Thus, the high risk of cancers of the esophagus and cervix uteri in blacks (relative to whites) and colorectal cancers in whites show little change over time. Conversely, the odds of breast cancer, on average four times higher in whites than blacks, has shown a significant decrease in the differential over time. Cancer of the prostate, with the odds initially (1991-1997) 15% higher in whites had become 33% higher in blacks by 2004-2010.

Prediction of cervical cancer incidence in England, UK, up to 2040, under four scenarios: a modelling study.

BACKGROUND: In the next 25 years, the epidemiology of cervical cancer in England, UK, will change: human papillomavirus (HPV) screening will be the primary test for cervical cancer. Additionally, the proportion of women screened regularly is decreasing and women who received the HPV vaccine are due to attend screening for the first time. Therefore, we aimed to estimate how vaccination against HPV, changes to the screening test, and falling screening coverage will affect cervical cancer incidence in England up to 2040. METHODS: We did a data modelling study that combined results from population modelling of incidence trends, observable data from the individual level with use of a generalised linear model, and microsimulation of unobservable disease states. We estimated age-specific absolute risks of cervical cancer in the absence of screening (derived from individual level data). We used an age period cohort model to estimate birth cohort effects. We multiplied the absolute risks by the age cohort effects to provide absolute risks of cervical cancer for unscreened women in different birth cohorts. We obtained relative risks (RRs) of cervical cancer by screening history (never screened, regularly screened, or lapsed attender) using data from a population-based case-control study for unvaccinated women, and using a microsimulation model for vaccinated women. RRs of primary HPV screening were relative to cytology. We used the proportion of women in each 5-year age group (25-29 years to 75-79 years) and 5-year period (2016-20 to 2036-40) who have a combination of screening and vaccination history, and weighted to estimate the population incidence. The primary outcome was the number of cases and rates per 100 000 women under four scenarios: no changes to current screening coverage or vaccine uptake and HPV primary testing from 2019 (status quo), changing the year in which HPV primary testing is introduced, introduction of the nine-valent vaccine, and changes to cervical screening coverage. FINDINGS: The status quo scenario estimated that the peak age of cancer diagnosis will shift from the ages of 25-29 years in 2011-15 to 55-59 years in 2036-40. Unvaccinated women born between 1975 and 1990 were predicted to have a relatively high risk of cervical cancer throughout their lives. Introduction of primary HPV screening from 2019 could reduce age-standardised rates of cervical cancer at ages 25-64 years by 19%, from 15·1 in 2016 to 12·2 per 100 000 women as soon as 2028. Vaccination against HPV types 16 and 18 (HPV 16/18) could see cervical cancer rates in women aged 25-29 years decrease by 55% (from 20·9 in 2011-15 to 9·5 per 100 000 women by 2036-40), and introduction of nine-valent vaccination from 2019 compared with continuing vaccination against HPV 16/18 will reduce rates by a further 36% (from 9·5 to 6·1 per 100 000 women) by 2036-40. Women born before 1991 will not benefit directly from vaccination; therefore, despite vaccination and primary HPV screening with current screening coverage, European age-standardised rates of cervical cancer at ages 25-79 years will decrease by only 10% (from 12·8 in 2011-15 to 11·5 per 100 000 women in 2036-40). If screening coverage fell to 50%, European age-standardised rates could increase by 27% (from 12·8 to 16·3 per 100 000 by 2036-40). INTERPRETATION: Going forward, focus should be placed on scenarios that offer less intensive screening for vaccinated women and more on increasing coverage and incorporation of new technologies to enhance current cervical screening among unvaccinated women. FUNDING: Jo's Cervical Cancer Trust and Cancer Research UK.