Allan Hildesheim

Cervicography screening for cervical cancer among 8460 women in a high- risk population

OBJECTIVEnCervicography was evaluated as a primary screening method for cervical cancer.nnnSTUDY DESIGNnCervigrams of 8460 women were taken on enrollment into a population-based study of cervical neoplasia. Cervicography results were compared with a referent diagnosis determined by histologic analysis and 3 cytologic tests, and with the performance of conventional cytologic evaluation.nnnRESULTSnCervicography identified all 11 cancers, whereas cytologic testing missed 1. Cervicography yielded sensitivities for detecting high-grade squamous intraepithelial lesions or cancer of 49.3% overall (specificity, 95.0%), 54.6% in women younger than 50 years of age, and 26.9% in women 50 years of age and older. Cytologic testing yielded sensitivities for detecting high-grade squamous intraepithelial lesions or cancer of 77.2% overall (specificity, 94. 2%), 75.5% in women younger than 50 years of age, and 84.6% in women 50 years of age and older.nnnCONCLUSIONSnCytologic testing performed better than cervicography for the detection of high-grade squamous intraepithelial lesions. Cervicography performed marginally better than cytologic testing for the detection of invasive cervical cancer. Cervicography is not recommended for postmenopausal women.

Evaluation of a Novel PCR-Based Assay for Detection and Identification of Chlamydia trachomatis Serovars in Cervical Specimens

ABSTRACT The aims of this study were to compare a novel PCR-based Chlamydia trachomatis detection and genotyping (Ct-DT) assay with the FDA-approved, commercially available C. trachomatis detection Hybrid Capture 2 (HC2) assay and to investigate the C. trachomatis serovar distribution among young women in a rural Costa Rican study population. A total of 5,828 sexually active women participating in a community-based trial in Costa Rica were tested for C. trachomatis by HC2. A sample of 1,229 specimens consisting of 100% HC2 C. trachomatis-positive specimens (n = 827) and a random sample of 8% HC2 C. trachomatis-negative specimens (n = 402) were tested with the Ct-DT assay. Agreement between the two assays was determined by the unweighted kappa statistic. Discrepant specimens were tested with a second commercially available test (COBAS TaqMan). The Ct-DT-positive specimens were further analyzed with the Ct-DT genotyping step to investigate the distribution of 14 different C. trachomatis serovars (A, B/Ba, C, D/Da, E, F, G/Ga, H, I/Ia, J, K, L1, L2/L2a, and L3). After accounting for the sampling fraction selected for Ct-DT testing, crude agreement with the HC2 assay was 98% and the kappa was 0.92 (95% confidence interval [CI], 0.89 to 0.97). The 33 discordant samples that were further analyzed with the COBAS TaqMan test showed better agreement with the Ct-DT assay (31/33, P < 0.001). Among the 806 Ct-DT-positive samples, serovar E was the most common serovar (31%), followed by serovars F and D (both 21%) and serovar I (15%). In conclusion, the novel Ct-DT assay permits reliable detection and identification of C. trachomatis serovars.

CorrespondenceHPV vaccination in women aged 24–45 years

The evidence is clear. HPV virus like particle (VLP) vaccines are highly effective in preventing persistent HPV infection and related cervical disease in girls and women naive to the relevant HPV type(s). However, what remains unclear is the public health benefit (PHB) to be derived from vaccination of mid adult women 24-45: the age cohort considered in the study by Munoz et al1. Heres why: n nIn the trial, the vaccine efficacy (VE) in the per-protocol population was 90% for disease or infection related to HPV 6, 11, 16, and 18. VE is the appropriate metric to answer the focused question of whether the vaccine is able to prevent infection and disease in women naive to the relevant HPV type. However this is not the best metric to evaluate the PHB of vaccination. To assess PHB, a different cohort, disease endpoint and metric may be considered. n n nCohort: Analysis of PHB should use the intention-to-treat population rather than the per-protocol cohort that excludes women with pre-existing infections and women who do not complete the full course of vaccination. (VE in the intention to treat population was only 31% in the Munoz study). It also should evaluate the generalizability of results from the cohort to the target population. n n nEndpoint: Newly-detected infections that persist for 6 months may be a reasonable surrogate endpoint for evaluating VE, however PHB should be based on the reduction in an endpoint close to the disease targeted for prevention (i.e. CIN2+, or better yet CIN3+, as surrogates for cancer risk). In the Munoz study, virtually all the endpoints were either persistent infection or CIN1 (which the authors admit is considered a manifestation of productive HPV infection). The number of cases of CIN2+ is not reported. n n nMetric: A relative ratio of disease reduction as measured by VE, does not account for the incidence of disease (attack rate) in the unvaccinated population in contrast to an absolute rate reduction of disease (e.g. how many cases averted per 1,000 women vaccinated). To illustrate the importance of attack rate in assessing PHB, consider these examples: a vaccine with only 50% VE against a disease that would affect 20% of the population will prevent 100 events per 1,000 vaccinated, while a vaccine with 90% VE against a disease that would strike 1.0% of the population will prevent only 9 events per 1,000 vaccinated. n n n nRecent data provide evidence that new HPV infections in older, sexually-experienced women carry only a low risk of developing into CIN2+. 2 In the Munoz study, 25 “cases” of persistent HPV-16 and/or HPV-18 persistent infection or disease (largely CIN1) were averted in almost 4000 person-years of follow-up. If 10% of these infections would have been expected to develop into CIN2 or worse, then the extrapolated PHB of vaccinating women 24-45 would be prevention of 1.33 cases of CIN2+/1000 women over two years. n nHPV vaccination is expensive. It is clear that targeting young women prior to sexual debut will provide the greatest benefit from HPV vaccination for a given cost. The peak of CIN2/3 occurs in women in their late-20s and early 30s---HPV vaccination must precede the acquisition of those causal HPV infections that occurred 5-10 years earlier.3 PHB and cost-effectiveness, not just VE, should be considered before establishing vaccination recommendations.1 Muñoz N, Manalastas R, Pitisultithum P, et al. Safety, immunogenicity, and effi cacy of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine in women aged 24–45 years: a randomised, double-blind trial. Lancet 2009; 373: 1949–57. 2 Dunne E. ACIP considerations: vaccination of women 27-45 years. Quadrivalent HPV vaccine. Presented at the Meeting of the Advisory Committee on Immunization Practices (ACIP); Atlanta,GA, USA; June 25, 2008.