Pooled Analysis of a Self-Sampling HPV DNA Test as a Cervical Cancer Primary Screening Method

BackgroundWorldwide, one-seventh of cervical cancers occur in China, which lacks a national screening program. By evaluating the diagnostic accuracy of self-collected cervicovaginal specimens tested for human papillomavirus (HPV) DNA (Self-HPV testing) in China, we sought to determine whether Self-HPV testing may serve as a primary cervical cancer screening method in low-resource settings.MethodsWe compiled individual patient data from five population-based cervical cancer–screening studies in China. Participants (n = 13 140) received Self-HPV testing, physician-collected cervical specimens for HPV testing (Physician-HPV testing), liquid-based cytology (LBC), and visual inspection with acetic acid (VIA). Screen-positive women underwent colposcopy and confirmatory biopsy. We analyzed the accuracies of pooled Self-HPV testing, Physician-HPV testing, VIA, and LBC to detect biopsy-confirmed cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) and CIN3+. All statistical tests were two-sided.ResultsOf 13 004 women included in the analysis, 507 (3.9%) were diagnosed as CIN2+, 273 (2.1%) as CIN3+, and 37 (0.3%) with cervical cancer. Self-HPV testing had 86.2% sensitivity and 80.7% specificity for detecting CIN2+ and 86.1% sensitivity and 79.5% specificity for detecting CIN3+. VIA had statistically significantly lower sensitivity for detecting CIN2+ (50.3%) and CIN3+ (55.7%) and higher specificity for detecting CIN2+ (87.4%) and CIN3+ (86.9%) (all P values < .001) than Self-HPV testing, LBC had lower sensitivity for detecting CIN2+ (80.7%, P = .015), similar sensitivity for detecting CIN3+ (89.0%, P = .341), and higher specificity for detecting CIN2+ (94.0%, P < .001) and CIN3+ (92.8%, P < .001) than Self-HPV testing. Physician-HPV testing was more sensitive for detecting CIN2+ (97.0%) and CIN3+ (97.8%) but similarly specific for detecting CIN2+ (82.7%) and CIN3+ (81.3%) (all P values <.001) than Self-HPV testing.ConclusionsThe sensitivity of Self-HPV testing compared favorably with that of LBC and was superior to the sensitivity of VIA. Self-HPV testing may complement current screening programs by increasing population coverage in settings that do not have easy access to comprehensive cytology-based screening

HPV type-specific risks of high-grade CIN during 4 years of follow-up: A population-based prospective study

We followed a population-based cohort of 5696 women, 32–38 years of age, by registry linkage with cytology and pathology registries during a mean follow-up time of 4.1 years to assess the importance for CIN2+ development of type-specific HPV DNA positivity at baseline. HPV 16, 31 and 33 conveyed the highest risks and were responsible for 33.1, 18.3 and 7.7% of CIN2+ cases, respectively. Women infected with HPV 18, 35, 39, 45, 51, 52, 56, 58, 59 and 66 had significantly lower risks of CIN2+ than women infected with HPV 16. After adjustment for infection with other HPV types, HPV types 35, 45, 59 and 66 had no detectable association with CIN2+. In summary, the different HPV types found in cervical cancer show distinctly different CIN2+ risks, with high risks being restricted to HPV 16 and its close relatives HPV 31 and HPV 33

Population-based human papillomavirus 16, 18, 6 and 11 DNA positivity and seropositivity in Chinese women

To optimize HPV vaccination implementation at the population-level in China, data are needed on age-specific HPV 16, 18, 6 and 11 prevalence. This cross-sectional, population-based study evaluated the age- and type-specific HPV 16, 18, 6 and 11 prevalence of DNA and serum antibodies among women in China. From July 2006 to April 2007, 17-54 year old women from three rural provinces (Xinjiang, Shanxi and Henan) and two cities (Beijing and Shanghai) provided cervical exfoliated cells for HPV DNA and liquid-based cervical cytology (SurePath). High- and low-risk HPV types were detected with HC-II (Qiagen), with genotyping of HPV-positive samples using Linear Array (Roche). HPV 16, 18, 6 and 11 serum antibodies were detected using a Luminex-based, competitive immunoassay (Merck). A total of 4,206 women with DNA and serum antibody results were included. HPV 16 DNA prevalence peaked in women aged 30-34 (4.2%) and 45-49 yr (3.8%), while HPV 18 DNA prevalence peaked at ages 40-44 yr (1.3%). Most women were dually DNA and serum antibody negative: HPV 16 (92.2%), 18 (97.2%), HPV 16 and 18 (90.2%), 6 (92.0%), 11 (96.6%), 6 and 11(89.9%) and HPV 16, 18, 6 and 11 (82.5%). Future national HPV vaccination programs in China should target younger women due to increased exposure to HPV types 16, 18, 6 and 11 with increasing age. Cumulative exposure of HPV may be underreported in this population, as cross-sectional data do not accurately reflect exposure to HPV infections over time

Weekly platinum chemotherapy for recurrent ovarian cancer

British Journal of Cancer (2002) 86, 2–4. DOI: 10.1038/sj/bjc/6600062 www.bjcancer.co

Different cervical cancer screening approaches in a Chinese multicentre study

To evaluate alternative cervical cancer screening methods, digital colposcopy and collection of cervical exfoliated cells for liquid-based cytology (LBC) and hybrid capture 2 (HC2) testing were performed among 2562 women aged 15–59 years in three study sites in the People's Republic of China (rural Shanxi province, Shenyang city in Liaoning province and Shenzhen city in Guangdong province). Visual inspection with acetic acid (VIA) was also evaluated independently from colposcopy. A total of 74 cases of histologically confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) were identified, and 16 CIN2+ cases were imputed among unbiopsied women to correct for verification bias. Corrected sensitivity for CIN2+ was 37% for VIA, 54% for colposcopy, 87% for LBC with a threshold of atypical cells of undetermined significance (LBC⩾ASCUS), 90% for HC2, 84% for LBC using HC2 to triage ASCUS and 96% for positivity to LBC⩾ASCUS or HC2. For VIA, sensitivity was much lower among women ⩾40 years (12%) than those aged ⩽39 years (50%). Specificity varied from 77% for positivity to LBC⩾ASCUS or HC2, up to 94% for LBC using HC2 to triage ASCUS. In conclusion, LBC, HC2 and their combinations performed well, whereas VIA missed a majority of CIN2+, particularly in older women. Digital colposcopy performed better than VIA, but still missed nearly half of CIN2+ in this study

Low-Density Lipoprotein Receptor-Related Protein 1 (LRP1) Mediates Neuronal Aβ42 Uptake and Lysosomal Trafficking

Alzheimer's disease (AD) is characterized by the presence of early intraneuronal deposits of amyloid-beta 42 (Abeta42) that precede extracellular amyloid deposition in vulnerable brain regions. It has been hypothesized that endosomal/lysosomal dysfunction might be associated with the pathological accumulation of intracellular Abeta42 in the brain. Our previous findings suggest that the LDL receptor-related protein 1 (LRP1), a major receptor for apolipoprotein E, facilitates intraneuronal Abeta42 accumulation in mouse brain. However, direct evidence of neuronal endocytosis of Abeta42 through LRP1 is lacking.Here we show that LRP1 endocytic function is required for neuronal Abeta42 uptake. Overexpression of a functional LRP1 minireceptor, mLRP4, increases Abeta42 uptake and accumulation in neuronal lysosomes. Conversely, knockdown of LRP1 expression significantly decreases neuronal Abeta42 uptake. Disruptions of LRP1 endocytic function by either clathrin knockdown or by removal of its cytoplasmic tail decreased both uptake and accumulation of Abeta42 in neurons. Finally, we show that LRP1-mediated neuronal accumulation of Abeta42 is associated with increased cellular toxicity.These results demonstrate that LRP1 endocytic function plays an important role in the uptake and accumulation of Abeta42 in neuronal lysosomes. These findings emphasize the central function of LRP1 in neuronal Abeta metabolism

A second generation cervico-vaginal lavage device shows similar performance as its preceding version with respect to DNA yield and HPV DNA results

Contains fulltext : 118480.pdf (publisher's version ) (Open Access)BACKGROUND: Attendance rates of cervical screening programs can be increased by offering HPV self-sampling to non-attendees. Acceptability, DNA yield, lavage volumes and choice of hrHPV test can influence effectiveness of the self-sampling procedures and could therefore play a role in recruiting non-attendees. To increase user-friendliness, a frequently used lavage sampler was modified. In this study, we compared this second generation lavage device with the first generation device within similar birth cohorts. METHODS: Within a large self-sampling cohort-study among non-responders of the Dutch cervical screening program, a subset of 2,644 women received a second generation self-sampling lavage device, while 11,977 women, matched for age and ZIP-code, received the first generation model. The second generation device was different in shape, color, lavage volume, and packaging, in comparison to its first generation model. The Cochran's test was used to compare both devices for hrHPV positivity rate and response rate. To correct for possible heterogeneity between age and ZIP codes in both groups the Breslow-Day test of homogeneity was used. A T-test was utilized to compare DNA yields of the obtained material in both groups. RESULTS: Median DNA yields were 90.4 mug/ml (95% CI 83.2-97.5) and 91.1 mug/ml (95% CI 77.8-104.4, p= 0.726) and hrHPV positivity rates were 8.2% and 6.9% (p= 0.419) per sample self-collected by the second - and the first generation of the device (p= 0.726), respectively. In addition, response rates were comparable for the two models (35.4% versus 34.4%, p= 0.654). CONCLUSIONS: Replacing the first generation self-sampling device by an ergonomically improved, second generation device resulted in equal DNA yields, comparable hrHPV positivity rates and similar response rates. Therefore, it can be concluded that the clinical performance of the first and second generation models are similar. Moreover, participation of non-attendees in cervical cancer screening is probably not predominantly determined by the type of self-collection device

Improving behaviour in self-testing (IBIS): Study on frequency of use, consequences, information needs and use, and quality of currently available consumer information (protocol)

<p>Abstract</p> <p>Background</p> <p>Self-tests are available to consumers for more than 25 conditions, ranging from infectious diseases to cardiovascular risk factors. Self-tests are defined as in-vitro tests on body materials such as blood, urine, faeces, or saliva that are initiated by consumers to diagnose a particular disorder or risk factor without involving a medical professional. In 2006, 16% of a sample of Dutch Internet users had ever used at least one self-test and 17% intended to use a self-test in the future. The objectives of this study are to determine (1) the frequency of self-test use, (2) the consumers' reasons for using or not using a self-test, (3) the information that is used by self-testers in the different self-test stages and the consumers' interpretation of the quality of this information, (4) the consumers' response to self-test results in terms of their confidence in the result, reassurance by the test result, and follow-up behaviour, (5) the information consumers report to need in the decision making process of using or not using a self-test, and in further management on the basis of the self-test result, and (6) the quality of the currently available consumer information on a selected set of self-tests.</p> <p>Methods</p> <p>Mixed methods study with (1) a cross-sectional study consisting of a two-phase Internet-questionnaire, (2) semi-structured interviews with self-testers and consumers who intend to use a self-test, and (3) the assessment of the quality of consumer information of self-tests. The Health Belief Model and the Theory of Planned Behaviour will serve as the theoretical basis for the questionnaires and the interview topic guides.</p> <p>Conclusions</p> <p>The self-testing area is still in a state of flux and therefore it is expected that self-test use will increase in the future. To the best of our knowledge, this is the first study which combines quantitative and qualitative research to identify consumers' information needs and use concerning self-testing, and the consumers' actual follow-up behaviour based on the self-test result, and simultaneously investigates the quality of the currently available consumer information. The results of this study will be used as an input in developing consumer information on self-testing.</p