The serial interval of an infectious disease represents the duration between symptom onset of a primary case and symptom onset of its secondary cases. A good evidence base for such values is essential, because they allow investigators to identify epidemiologic links between cases and serve as an important parameter in epidemic transmission models used to design infection control strategies. We reviewed the literature for available data sets containing serial intervals and for reported values of serial intervals. We were able to collect data on outbreaks within households, which we reanalyzed to infer a mean serial interval using a common statistical method. We estimated the mean serial intervals for influenza A(H3N2) (2.2 days), pandemic influenza A(H1N1)pdm09 (2.8 days), respiratory syncytial virus (7.5 days), measles (11.7 days), varicella (14.0 days), smallpox (17.7 days), mumps (18.0 days), rubella (18.3 days), and pertussis (22.8 days). For varicella, we found an evidence-based value that deviates substantially from the 21 days commonly used in transmission models. This value of the serial interval for pertussis is, to the best of our knowledge, the first that is based on observations. Our review reveals that, for most infectious diseases, there is very limited evidence to support the serial intervals that are often cited.

Little is known about the time span of progression from high-grade cervical intraepithelial neoplasia (CIN2/3) to invasive cervical cancer. Estimation of this duration from longitudinal studies is not permitted, as CIN2/3 should be treated when detected. Cross-sectional data on the age-specific incidence of detected CIN2/3 and cervical cancer cases are readily available in national registries, but these data are difficult to interpret because neither the moment of lesion development nor the onset of invasive cancer is observed. We developed a statistical model for estimating the duration of time between CIN2/3 and preclinical cancer using Dutch national registries for the years 2000-2005. Human papillomavirus (HPV) genotype data were used to separate CIN2/3 and cancer incidences to obtain estimates for HPV-16-positive and HPV-16-negative lesions. The median time from CIN2/3 to cancer was estimated to be 23.5 years (95% confidence interval: 20.8, 26.6), and 1.6% of the lesions progressed to cancer within 10 years. The median duration for HPV-16-positive lesions was similar, but 2.4% of the HPV-16-positive lesions progressed to cancer within 10 years, as compared with 0.6% for HPV-16-negative lesions. Estimated durations of time to cancer are essential for reassessment of the optimal screening interval in light of vaccination and novel screening tests.

Our results provide a benchmark for examining the effect of HPV16 vaccination in future serological surveys. Our method may prove useful for estimating seroprevalence of other infections with a weak serological response.

Cytological screening has substantially decreased the cervical cancer incidence, but even better protection may be achieved by primary high-risk human papillomavirus (hrHPV) screening. In the Netherlands, five-yearly cytological screening for women aged 30-60 years will be replaced by primary hrHPV screening in 2016. The new screening guidelines involve an extension of the screening interval from 5 to 10 years for hrHPV-negative women aged 40 or 50 years. We investigated the impact of this program change on the lifetime cancer risks in women without an hrHPV infection at age 30, 35, 40, 45 or 50 years. The time to cancer was estimated using 14-year follow-up data from a population-based screening intervention trial and the nationwide database of histopathology reports. The new screening guidelines are expected to lead to a reduced cervical cancer risk for all age groups. The average risk reduction was 34% and was smallest (25%) among women aged 35 years. The impact of hrHPV screening on the cancer risk was sensitive to the duration from cervical intraepithelial neoplasia grade 2/3 (CIN2/3) to cancer; a small increase in the cancer risk was estimated for women aged 35 or 40 years in case a substantial proportion of CIN2/3 showed fast progression to cancer. Our results indicate that primary hrHPV screening with a ten-yearly interval for hrHPV-negative women of age 40 and beyond will lead to a further reduction in lifetime cancer risk compared to five-yearly cytology, provided that precancerous lesions progress slowly to cancer.Screening for cervical cancer has been implemented in many countries starting in the 1960s 1 and has led to a large reduction in cervical cancer incidence since. [2][3][4] Most countries use a cytology-based screening instrument (the Pap test). The success of cervical screening is largely determined by the opportunity for timely detection and treatment of precancerous lesions and the accuracy of the screening instrument. The time spent in the screen-detectable, precancerous state is thought to be long enough to prevent the majority of cervical cancer cases, 5,6 but the sensitivity of cytology for detection of cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3) is only moderate and varies considerably between countries (see for example Cuzick et al. 7 ). Repeated screening is therefore necessary to compensate for test inaccuracy.Cervical cancer is caused by a persistent high-risk human papillomavirus (hrHPV) infection. HrHPV testing has been shown to have a higher sensitivity than cytology for detection of CIN2/3 (96% vs. 53% 7 ) at the cost of a 2.5 to 4% lower specificity. 7,8 Moreover, hrHPV screening provides up to 70% better protection against CIN3 and cancer compared to cytology. 9,10 Despite its lower specificity, organized screening by hrHPV testing in cervical smears is considered cost-effective on the basis of modeling studies 11-13 and several countries are considering implementation of the hrHPV DNA test as primary screening instrument, either used alone or in combination wit...