Cervical cancer screening of HPV vaccinated populations: Cytology, molecular testing, both or none.

Cervical cancer control includes primary prevention through vaccination to prevent human papillomavirus (HPV) infection and secondary prevention through screening to detect and treat cervical precancerous lesions. This review summarizes the evidence for the population impact of vaccines against oncogenic HPV types in reducing the prevalence of cervical precancerous lesions. We examine the gradual shift in screening technology from cervical cytology alone to cytology and HPV cotesting, and finally to the recognition that HPV testing can serve alone as the new screening paradigm, particularly in the initial post-vaccination era. We should expect an impact on screening performance and practices, as cohorts of HPV-vaccinated girls and adolescents reach cervical cancer screening age. In preparation for changes in the screening paradigm for the vaccination era, we propose that policymaking on cervical cancer screening should mirror current practices with other cancers as benchmarks. Cervical precancerous lesions will become a very rare condition following the widespread implementation of HPV vaccines with broader coverage in the number of preventable oncogenic types. Irrespective of screening technology, the false positive results will far outnumber the true positive ones, a tipping point that will herald a new period when the harms from cervical cancer screening will outweigh its benefits. We present a conceptual framework to guide decision making when we reach this point within 25-30 years.

HPV DNA testing with cytology triage in cervical cancer screening: Influence of revealing HPV infection status.

BACKGROUND: Knowledge of cervical human papillomavirus (HPV) status might influence a cytotechnician's assessment of cellular abnormalities. The authors compared original cytotechnicians' Papanicolaou (Pap) readings for which HPV status was concealed with Pap rereads for which HPV status was revealed separately for 3 screening populations. METHODS: Previously collected cervical Pap smears and clinical data were obtained from the Canadian Cervical Cancer Screening Trial (study A), the Democratic Republic of Congo Community-Based Screening Study (study B), and the Brazilian Investigation into Nutrition and Cervical Cancer Prevention (study C). Smears were reread with knowledge of HPV status for all HPV-positive women as well as a sample of HPV-negative women. Diagnostic performance of Pap cytology was compared between original readings and rereads. RESULTS: A total of 1767 Pap tests were reread. Among 915 rereads for HPV-positive women, the contrast between "revealed" and "concealed" Pap readings demonstrated revisions from negative to positive results for 109 women (cutoff was atypical squamous cells of undetermined significance or worse) and 124 women (cutoff was low-grade squamous intraepithelial lesions [LSIL] or worse). For a disease threshold of cervical intraepithelial neoplasia of grade 2 or worse, specificity significantly declined at the atypical squamous cells of undetermined significance cutoff for studies A (86.6% to 75.3%) and C (42.5% to 15.5%), and at the LSIL cutoff for study C (61.9% to 37.6%). Sensitivity remained nearly unchanged between readings, except in study C, in which reread performance was superior (91.3% vs 71.9% for the LSIL cutoff). CONCLUSIONS: A reduction in the diagnostic accuracy of Pap cytology was observed when revealing patients' cervical HPV status, possibly due to a heightened awareness of potential abnormalities, which led to more false-positive results.

Epidemiology and burden of HPV infection and related diseases: implications for prevention strategies.

Human papillomavirus (HPV) infection is a necessary, although not sufficient cause of cervical cancer. Globally, HPV infection accounts for an estimated 530,000 cervical cancer cases (~270,000 deaths) annually, with the majority (86% of cases, 88% of deaths) occurring in developing countries. Approximately 90% of anal cancers and a smaller subset (<50%) of other cancers (oropharyngeal, penile, vaginal, vulvar) are also attributed to HPV. In total, HPV accounts for 5.2% of the worldwide cancer burden. HPVs 16 and 18 are responsible for 70% of cervical cancer cases and, especially HPV 16, for a large proportion of other cancers. Prophylactic vaccination targeting these genotypes is therefore expected to have a major impact on the burden of cervical cancer as well as that of other HPV-related cancers. Over the past 50 years, organized or opportunistic screening with Papanicolaou (Pap) cytology has led to major reductions in cervical cancer in most developed countries. However, due to lack of resources or inadequate infrastructure, many countries have failed to reduce cervical cancer mortality through screening. HPV DNA testing recently emerged as a likely candidate to replace Pap cytology for primary screening. It is less prone to human error and more sensitive than Pap in detecting high-grade cervical lesions. For countries with national vaccination programs, HPV testing may also serve as a low cost strategy to monitor long term vaccine efficacy. Introduction of well organized vaccination and screening programs should be a priority for all countries. Increased support from donors is needed to support this cause.

Patient preference to use a questionnaire varies according to attributes.

OBJECTIVE: Health care professionals may assume questionnaires are burdensome to patients, and this limits their use in clinical settings and promotes simplification. However, patient adherence may improve by optimizing questionnaire attributes and contexts. METHODS: This cross-sectional survey used Contingent Valuation methods to directly elicit patient preference for conventional monitoring of symptoms, versus adding a tool to monitoring. Under explicit consideration was the 10-question Edmonton Symptom Assessment System (ESAS). In the questionnaire, attributes of ESAS were sequentially altered to try and force preference reversal. A separate group of participants completed both questionnaire and interviews to explore questionnaire reliability, and extend validity. RESULTS: Overall, 24 of 43 participants preferred using ESAS. Most important attributes to preference were frequency, specificity, and complexity. Where preference is initially against ESAS, it may reverse by simplifying the tool and its administrative processes. Interviews in 10 additional participants supported reproducibility and validity of the questionnaire method. CONCLUSIONS: Preference for using tools increases when tools are made relevant and used more appropriately. PRACTICE IMPLICATIONS: Questionnaires completed by patients as screening tools or aids to communication may be under-utilized. Optimization of ESAS and similar tools may be guided by empirical findings, including those obtained from Contingent Valuation methodologies.

Optimizing technology for cervical cancer screening in high-resource settings.

Although historically successful in reducing the burden of cervical cancer, Papanicolaou (Pap) testing faces numerous limitations. A growing body of evidence suggests that modern screening practice will benefit from primary screening for high-risk human papillomavirus (HPV) infection, the causative agent of cervical cancer. Molecular tests detecting the presence of HPV nucleic acids consistently demonstrate high sensitivity relative to Pap testing, and provide reliable, dichotomous results. Pap cytology is ideally suited to triage HPV-positive cases owing to its high test specificity, and the accuracy of cytological readings will be maximized in high-prevalence conditions. This algorithm of primary HPV testing with Pap triage has been shown to maintain the high sensitivity of HPV testing without compromising Pap cytology's strong ability to rule out falsely positive diagnoses. Given the anticipated decline of high-risk HPV-16 and -18 infections in the emergent post-HPV vaccination era, highly sensitive primary HPV testing is especially warranted. Novel screening technologies that identify HPV viral gene expression continue to emerge and seek to complement current HPV testing by identifying those women who may be at risk of progressive disease. How to best incorporate these new technologies into clinical practice presents our next great challenge. Implementation of novel algorithms for cervical screening is not a trivial task. Avoidance of exceedingly complex screening algorithms is an important priority.