Cancer Screening Algorithms Research Articles

Performance of Roche cobas high-risk human papillomavirus (hrHPV) testing in the two most common liquid-based Papanicolaou test platforms

High-risk human papillomavirus (hrHPV) testing is important in cervical cancer screening and management algorithms. Roche (Pleasanton, Calif.) cobas hrHPV testing is commonly performed on both ThinPrep (TP) and SurePath (SP) samples, but performance of these platforms has not been fully investigated in the literature. Roche hrHPV testing was performed on 47,885 (TP = 18,295; SP = 29,590) out of 130,648 consecutive Papanicolaou tests, over 16 months; 1895 of those had interpretable biopsies. The overall hrHPV detection rates were similar in TP (13.5%) and SP (13.1%). The hrHPV positive rate was higher in SP (8.5%) than TP (7.3%, P < 0.0001) in women with negative cytology; the difference in other cytologic diagnosis categories was insignificant. TP samples had significantly fewer negative cytology diagnoses (7.3% versus 8.5%, P < 0.0001), more low-grade abnormalities in cytology and biopsies, and higher colposcopy referral rate (4.8% versus 2.7%, P < 0.0001) than SP. There were no differences between TP and SP in detecting ≥HSIL by hrHPV testing, cytology or biopsy. SP samples had a significantly higher rate of HPV 16/18 but a lower rate of non-16/18 hrHPV genotypes than TP. Roche cobas hrHPV testing was similar in both TP and SP platforms. The significantly lower hrHPV detection rate in cytological negative TP samples is likely related to higher cytology reporting rates for indeterminate and low-grade diagnoses in TP than SP samples. Significant differences were also observed in hrHPV genotyping results between TP and SP. Clinical risk stratification based on hrHPV testing may need to take testing platforms into consideration.

Mobile Application Use Among Obstetrics and Gynecology Residents.

Mobile applications (apps) are increasingly used in clinical settings, particularly among resident physicians. Apps available to patients and physicians are rapidly expanding. We aimed to describe obstetrics and gynecology (ob-gyn) residents' use of and attitudes toward ob-gyn-related mobile apps. We conducted a cross-sectional survey of residents at all 19 California ob-gyn programs using a web-based questionnaire. Responses were analyzed using descriptive and chi-square statistics. Of 386 residents contacted, 197 (51%) completed the survey. All respondents owned mobile devices (100% smartphone, 74% tablet), and 93% used apps in the clinical setting. Commonly used ob-gyn-related apps were pregnancy wheels (84%), cervical cancer screening algorithms (68%), and contraceptive eligibility guidelines (47%). Only 53% of respondents recommended apps to patients, with many reporting not being aware of appropriate apps. Sixty-two percent of respondents used apps for learning, but only 3 ob-gyn-specific apps were mentioned. Most chose apps based on recommendations from other residents. Residents viewed mobile technology as an important clinical tool (92%) that improves efficiency (89%). App use did not differ by gender, age, or postgraduate year. Mobile technology and ob-gyn-related app use are widely used among California ob-gyn residents, who feel that apps enhance their ability to care for patients. Context of app use varies, with most residents using apps during clinical care, but only half recommending apps to patients. Recommendations from other residents are the common resource for discovering new apps, suggesting a need for more formal guidance on finding and evaluating apps.

Evaluation of cytology versus human papillomavirus-based cervical cancer screening algorithms in Bhutan.

To evaluate the performance of existing versus alternative cervical cancer screening protocols in Bhutan, cervical exfoliated cells were collected for cytology and high-risk human papillomavirus (HR-HPV) testing among 1,048 women aged 30-69 years. Conventional smears were prepared and read locally. HR-HPV was tested by GP5+/6+ polymerase chain reaction, followed by genotyping and human DNA methylation analysis among HR-HPV-positives, in Europe. Test positivity was 7.5% for ASCUS or worse (ASCUS+) cytology and 14.0% for HR-HPV. All women with ASCUS+ and/or HR-HPV positivity (n=192) were recalled for colposcopy, among whom a total of 29 cases of histologically confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) were identified. An additional 7 CIN2+ cases were imputed among women without colposcopy. Corrected sensitivities for CIN2+ and CIN3+ were 61% and 74% for ASCUS+, 86% and 96% for HR-HPV, and 47% and 70% for ASCUS+ triage of HR-HPV. Specificity varied from 88% for HR-HPV up to 98% for ASCUS+ triage of HR-HPV, similarly for CIN2+ and CIN3+. Among HR-HPV-positive women with biopsies, methylation analysis offered similar discrimination of CIN2/3 and cervical cancer as ASCUS+, and better than HPV16/18 genotyping alone, but sample sizes were limited. In conclusion, the performance of cytology in Bhutan is in the mid-range of that reported in other screening settings. HR-HPV testing has the potential to improve detection of CIN2+, albeit with a higher referral rate for colposcopy. Cytological triage of HR-HPV-positives (performed in the absence of knowledge of HR-HPV status) reduced referral but missed more than one third of CIN2+.

A Survey of Mobile App Use Among California Obstetrics and Gynecology Residents [8I

INTRODUCTION: Mobile applications (apps) are increasingly used in the clinical setting. We aimed to describe the attitudes and practices regarding OB/GYN-related mobile apps among OB/GYN residents. METHODS: We sent web-based questionnaires to residents at all 17 California OB/GYN programs. Responses were analyzed using descriptive and chi-square statistics. RESULTS: The survey was completed by 197 residents (response rate 51%). All respondents owned mobile devices (100% smartphone, 74% tablet), and 95% used apps in the clinical setting. The most commonly used OB/GYN-related apps were pregnancy wheels (84%), cervical cancer screening algorithms (68%), and contraceptive eligibility guidelines (47%). Fewer (52%) residents recommended apps to patients, many citing not knowing of any. The majority of residents (62%) used mobile apps for their own learning, most commonly the American College of Obstetricians and Gynecologists app. Most chose apps based on recommendations from other residents. Residents viewed mobile technology as an important clinical tool (92%) that improves efficiency (89%). Mobile app use was not associated with gender, age, or year in residency (p&gt;0.05 for each). CONCLUSION: Mobile technology and OB/GYN-related app use are ubiquitous among California OB/GYN residents, who feel that apps enhance their ability to care for patients. Because residents primarily choose apps based on the recommendation of other residents, leaders in resident education may consider evaluating app content and providing recommendations for app use. There is also opportunity to expand mobile app technology as a learning interface to enhance resident education.

Triage amalgamated dermoscopic algorithm (TADA) for skin cancer screening.

ImportanceDermoscopic triage algorithms have been shown to improve beginners’ abilities for identifying pigmented skin lesions requiring biopsy.ObjectiveTo estimate the diagnostic accuracy of the Triage Amalgamated Dermoscopic Algorithm (TADA) for pigmented and nonpigmented skin cancers. Secondarily, to compare TADAs performance to those of existing triage algorithms for the identification of pigmented skin cancers.DesignCross-sectional, observational, reader study that took place at a beginner and intermediate level dermoscopy course.ParticipantsTwo hundred medical professionals of various specialties attended the course and 120 voluntarily joined the study (60% participation rate).ExposuresAfter receiving basic dermoscopy training, participants evaluated 50 polarized, dermoscopic images of pigmented (22 benign, 18 malignant) and nonpigmented (1 benign, 9 malignant) skin lesions using TADA. Pigmented lesions were also evaluated using the Three-Point Checklist and AC Rule. With TADA, participants first determined if a lesion was an unequivocal angioma, dermatofibroma, or seborrheic keratosis, which would exclude it from further evaluation. All other lesions were assessed for architectural disorder, starburst pattern, blue-black or gray color, shiny white structures, negative network, ulcer/erosion, or vessels. Any one feature indicated suspicion for malignancy.ResultsMost participants were dermatologists (n=64, 53.3%) or primary care physicians (n=41, 34.2%), and many lacked previous dermoscopy training (n=52, 43.3%). TADA’s sensitivity and specificity for all skin cancers was 94.6% (95% CI=93.4–95.7%) and 72.5% (95% CI=70.1–74.7%), respectively. For pigmented skin cancers, the sensitivity and specificity were 94.0% (95% CI=92.9–95.0%) and 75.5% (95% CI=73.8–77.2%). This compared to 71.9% (95%CI=69.8–73.9%) and 81.4% (95%CI=79.7–83.0%) for the Three-Point Checklist and 88.6% (95%CI=87.1–89.9%) and 78.7% (95%CI=76.9–80.3%) for the AC Rule.ConclusionsThese results suggest that TADA compares favorably to existing triage algorithms and might be a useful triage tool with high sensitivity and specificity for pigmented and nonpigmented skin cancers. Further studies are needed to validate these preliminary observations.

Differential HPV16 variant distribution in squamous cell carcinoma, adenocarcinoma and adenosquamous cell carcinoma.

Human Papillomavirus 16 (HPV16) causes 70% of invasive cervical cancers (ICC) worldwide. Interaction between HPV16 genetic diversity, host genetics and target tissue largely determine the chances to trigger carcinogenesis. We have analyzed the differential prevalence of viral variants in 233 HPV16-monoinfected squamous (SCC), glandular (ADC) and mixed (ADSC) ICCs from four continents, assessing the contribution of geographical origin and cancer histology. We have further quantified the contribution of viral variants and cancer histology to differences in age at tumor diagnosis. The model fitted to the data explained 97% of the total variance: the largest explanatory factors were differential abundance among HPV16 variants (78%) and their interaction with cancer histology (9.2%) and geography (10.1%). HPV16_A1-3 variants were more prevalent in SCC while HPV16_D variants were increased in glandular ICCs. We confirm further a non-random geographical structure of the viral variants distribution. ADCs were diagnosed at younger ages than SCCs, independently of the viral variant triggering carcinogenesis. HPV16 variants are differentially associated with histological ICCs types, and ADCs are systematically diagnosed in younger women. Our results have implications for the implementation of cervical cancer screening algorithms, to ensure proper early detection of elusive ADCs.

Comparison of cytology, HPV DNA testing and HPV 16/18 genotyping alone or combined targeting to the more balanced methodology for cervical cancer screening

ObjectivesThe objective of the present study was to identify the most effective cervical cancer screening algorithm incorporating different combinations of cytology, HPV testing and genotyping. MethodsWomen 25–55years old recruited for the “HERMES” (HEllenic Real life Multicentric cErvical Screening) study were screened in terms of cytology and high-risk (hr) HPV testing with HPV 16/18 genotyping. Women positive for cytology or/and hrHPV were referred for colposcopy, biopsy and treatment. Ten screening algorithms based on different combinations of cytology, HPV testing and HPV 16/18 genotyping were investigated in terms of diagnostic accuracy. ResultsThree clusters of algorithms were formed according to the balance between effectiveness and harm caused by screening. The cluster showing the best balance included two algorithms based on co-testing and two based on HPV primary screening with HPV 16/18 genotyping. Among these, hrHPV testing with HPV 16/18 genotyping and reflex cytology (atypical squamous cells of undetermined significance - ASCUS threshold) presented the optimal combination of sensitivity (82.9%) and specificity relative to cytology alone (0.99) with 1.26 false positive rate relative to cytology alone. ConclusionHPV testing with HPV 16/18 genotyping, referring HPV 16/18 positive women directly to colposcopy, and hrHPV (non 16/18) positive women to reflex cytology (ASCUS threshold), as a triage method to colposcopy, reflects the best equilibrium between screening effectiveness and harm. Algorithms, based on cytology as initial screening method, on co-testing or HPV primary without genotyping, and on HPV primary with genotyping but without cytology triage, are not supported according to the present analysis.

Correlation of High Body Mass Index With More Advanced Localized Prostate Cancer at Radical Prostatectomy Is Not Reflected in PSA Level and PSA Density but Is Seen in PSA Mass.

Prostate cancer screening algorithms and preoperative nomograms do not include patients' body mass index (BMI). We evaluated outcomes at radical prostatectomy (RP) adjusted to BMI. Serum prostate-specific antigen (PSA) levels, PSA mass, PSA density (PSAD), and RP findings were analyzed with respect to BMI in 4,926 men who underwent RP between 2005 and 2014. In total, 1,001 (20.3%) men were normal weight, 2,547 (51.7%) were overweight, and 1,378 (28%) were obese. Median PSA levels (ng/mL) were normal weight, 5.0; overweight, 5.1; and obese, 5.2 (P = .094). Median PSA mass increased with increasing BMI: 15.9 vs 17.4 vs 19.4 μg (P < .001). Median PSAD was not significantly different: 0.11 vs 0.11 vs 0.11 ng/mL/g (P = .084). Median prostate weight increased with increasing BMI: 44 vs 45 vs 49 g (P < .001). Median prostatectomy tumor volume increased with increasing BMI: 3.9 vs 4.7 vs 5.9 cm(3) (P < .001). Overweight and obese patients had a higher Gleason score and more locally advanced cancer (P < .001). Frequency of positive surgical margins increased with higher BMIs (P < .001). Frequency of lymph node metastasis did not differ significantly (P = .088). While BMI correlates with tumor volume, Gleason score, and extent of disease at RP, there is no routinely measured clinical parameter reflecting this. Only PSA mass highlights this correlation. Thus, BMI and potentially PSA mass should be taken into account in predictive algorithms pertaining to prostate cancer and its surgical treatment.

The comparative and cost-effectiveness of HPV-based cervical cancer screening algorithms in El Salvador.

Cervical cancer is the leading cause of cancer death among women in El Salvador. Utilizing data from the Cervical Cancer Prevention in El Salvador (CAPE) demonstration project, we assessed the health and economic impact of HPV-based screening and two different algorithms for the management of women who test HPV-positive, relative to existing Pap-based screening. We calibrated a mathematical model of cervical cancer to epidemiologic data from El Salvador and compared three screening algorithms for women aged 30-65 years: (i) HPV screening every 5 years followed by referral to colposcopy for HPV-positive women (Colposcopy Management [CM]); (ii) HPV screening every 5 years followed by treatment with cryotherapy for eligible HPV-positive women (Screen and Treat [ST]); and (iii) Pap screening every 2 years followed by referral to colposcopy for Pap-positive women (Pap). Potential harms and complications associated with overtreatment were not assessed. Under base case assumptions of 65% screening coverage, HPV-based screening was more effective than Pap, reducing cancer risk by ∼ 60% (Pap: 50%). ST was the least costly strategy, and cost $2,040 per year of life saved. ST remained the most attractive strategy as visit compliance, costs, coverage, and test performance were varied. We conclude that a screen-and-treat algorithm within an HPV-based screening program is very cost-effective in El Salvador, with a cost-effectiveness ratio below per capita GDP.

Comparing Rates of High-Grade Squamous Intraepithelial Lesions (HSIL) in Patients Complying With a Cervical Cancer Screening Algorithm Versus Those who Fail to Comply Shows Significant Results

At Denver Health and Hospital Authority (DHHA) all female patients between the ages of 21 and 65 years are screened according to the clinical care guideline/algorithm for cervical cancer screening adopted by the medical staff using recommendations from American College of Obstetrics and Gynecology (ACOG), American Society for Colposcopy and Cervical Pathology (ASCCP), …

A study of borderline positive Hybrid Capture 2 tests in the Kaiser Permanente Northern California cervical screening program: Evidence against retesting

Infection with one or more high-risk HPV (hr-HPV) types is a necessary step in the development of cervical cancer, making its detection a useful tool for cervical cancer screening and prevention (Bosch et al., 2002). Hybrid Capture 2 (HC2, Qiagen, Gaithersburg, MD) was the first FDA-approved and is still the most widely used laboratory test for the presence of high-risk HPV DNA as a predictor of who is or is not at risk for cervical cancer and pre-cancer (defined here as cervical intraepithelial neoplasia grade 2 or worse). While HC2 has remarkable sensitivity for cervical intraepithelial neoplasia grade 2 or worse, the transient nature of most hr-HPV infections reduces its specificity as most infections are benign and will resolve without progressing to cervical intraepithelial neoplasia grade 2 or worse. This can be problematic for cervical cancer screening algorithms in which HPV positivity triggers more intensive follow-up; in such algorithms, good specificity is important for reducing the number of costly colposcopic follow-up visits (Cuzick et al., 2008). Although manufacturer specifications indicate a relative light unit (RLU) ratio compared with positive control of 1.0 as the threshold for determining positivity, reclassifying HC2 specimens that are equivocal and fall just above the positive cut-off is one potential way to improve the assay’s specificity (Rijkaart et al., 2010; Rebolj et al., 2011; Sasieni and Castanon, 2011). Some researchers have looked at increasing the RLU cut-off point because HC2 results at this level predict lower risk than higher values (Lorincz et al., 2002). However, equivocal results are not that common and raising the cut-point to 2.0 or 3.0 may only yield a modest improvement in specificity at some cost to sensitivity; i.e., misclassification of women with cervical intraepithelial neoplasia grade 2 or worse lesions whose RLU ratios are equivocal (Rijkaart et al., 2010). Rather than raising the cut-point, a more conservative approach is to repeat the HC2 test on specimens with equivocal results and determine the final test result based on a collective assessment of the test results (Knoepp et al., 2007), however this method requires additional laboratory time and cost to implement, weighing against any savings it yields from reducing the number of colposcopic examinations. In 2001 Kaiser Permanente Northern California added the HC2 assay to its cervical cancer screening program as a triage test for women with a cytologic diagnosis of atypical squamous cells of undetermined significance and, in 2003, as a concurrent test (“cotest”) with cytology for women 30 and older. In the cotesting scheme, women have been managed as follows: 1) women who are HPV-positive with a cytologic diagnosis of atypical squamous cells of undetermined significance, or have more severe (regardless of the HPV test results) are referred for immediate colposcopy; 2) women who test HPV-negative and have cytology of atypical squamous cells of undetermined significance, or who test HPV-positive with negative cytology are rescreened in one year; and 3) if both tests are negative, women are rescreened in three years. For cotests with borderline positive hr-HPV results, interpretation of the repeat test results is used to determine the final hr-HPV test result and hence the need for rescreening visits versus colposcopy. At the time that HC2 was introduced into the Kaiser Permanente Northern California cervical cancer screening algorithm, based on concern over the meaning of borderline-positive HC2-positive results, it was decided that any specimens with borderline or “equivocal” HC2 results, defined as a RLU ratio greater than or equal to 1.0 but less than 3.0, would be re-tested two additional times. The final hr-HPV result was determined by the majority results of the three tests i.e., only one of the two repeats needed to be positive to have the final positive hr-HPV result. To assess the utility of Kaiser Permanente Northern California’s re-testing scheme for equivocal HC2 specimens, HC2 data, cytology results, and histological outcomes (less than cervical intraepithelial neoplasia grade 2, cervical intraepithelial neoplasia grade 2 or worse) were compiled for patients undergoing routine cervical cancer screening at Kaiser Permanente Northern California.

Cervical Cancer Screening in the Era of Human Papillomavirus Testing and Vaccination

Cervical cancer screening algorithms have changed with the introduction of testing for human papillomavirus (HPV) and better understanding of the natural history of HPV. This review was undertaken to present recent developments related to cervical cancer screening, with HPV testing as a focus. Specifically, guidelines now recommend initiating cervical cancer screening at age 21, stopping at age 65 to 70 if previous tests are normal, and screening no more than every 2 to 3 years. Human papillomavirus testing is now incorporated into guidelines for cervical cancer screening in the United States, with the major impact being the lengthening of recommended screening intervals. Primary screening with HPV testing, although not yet approved in the United States, may serve to increase access to care for the millions of underserved women worldwide who bear most of the burden of cervical cancer. Despite clear guidelines from authoritative sources, many clinicians (including midwives) overscreen women. In cervical cancer screening, as in many areas of women's health care, performing tests that are unlikely to result in useful information may lead to harm.

Clinical human papillomavirus detection forecasts cervical cancer risk in women over 18 years of follow-up.

To describe the long-term (≥ 10 years) benefits of clinical human papillomavirus (HPV) DNA testing for cervical precancer and cancer risk prediction. Cervicovaginal lavages collected from 19,512 women attending a health maintenance program were retrospectively tested for HPV using a clinical test. HPV positives were tested for HPV16 and HPV18 individually using a research test. A Papanicolaou (Pap) result classified as atypical squamous cells of undetermined significance (ASC-US) or more severe was considered abnormal. Women underwent follow-up prospectively with routine annual Pap testing up to 18 years. Cumulative incidence rates (CIRs) of ≥ grade 3 cervical intraepithelial neoplasia (CIN3+) or cancer for enrollment test results were calculated. A baseline negative HPV test provided greater reassurance against CIN3+ over the 18-year follow-up than a normal Pap (CIR, 0.90% v 1.27%). Although both baseline Pap and HPV tests predicted who would develop CIN3+ within the first 2 years of follow-up, only HPV testing predicted who would develop CIN3+ 10 to 18 years later (P = .004). HPV16- and HPV18-positive women with normal Pap were at elevated risk of CIN3+ compared with other HPV-positive women with normal Pap and were at similar risk of CIN3+ compared with women with a low-grade squamous intraepithelial Pap. HPV testing to rule out cervical disease followed by Pap testing and possibly combined with the detection of HPV16 and HPV18 among HPV positives to identify those at immediate risk of CIN3+ would be an efficient algorithm for cervical cancer screening, especially in women age 30 years or older.

Radical prostatectomy: value of prostate MRI in surgical planning

The introduction of serum prostate-specific antigen to the prostate cancer screening algorithm has led to an increase in prostate cancer diagnosis as well as a migration toward lower-stage cancer at the time of diagnosis. This stage migration has coincided with changes in treatment options; these include active surveillance, new therapies, and advances in surgical techniques. Use of robot-assisted radical prostatectomy (RARP) as a surgical technique has seen a significant increase over the past several years: the number of patients undergoing RARP has risen from 1% to 40% of all prostatectomies from 2001-2006 to as many as 80% in 2010. The robotic interface provides a 3D magnified view of the surgical field, intuitive instrument manipulation, motion scaling, tremor filtration, and excellent dexterity and range of motion. However, in some cases, the lack of tactile (haptic) feedback may limit the surgeon's decision making ability in assessing malignant involvement of the neurovascular bundles. Pre-operative planning relies on nomograms based on limited clinical and prostate biopsy information. The surgical decision to spare or resect the neurovascular bundles is based on clinical information which is not spatially or anatomically based. Advances in magnetic resonance imaging (MRI) may provide spatially localized information to fill this void and aid surgical planning, particularly for robotic surgeons. In this review, we discuss the potential role of pre-operative MRI in surgical planning for radical prostatectomy.

Predicting Prostate Biopsy Result in Men With Prostate Specific Antigen 2.0 to 10.0 ng/ml Using an Investigational Prostate Cancer Methylation Assay

The inadequacies of prostate specific antigen testing have created a need for novel markers for prostate cancer screening. The investigational ProCaM™ prostate cancer methylation assay detects aberrant methylation of DNA in cells associated with prostate cancer. We describe a large, prospective, multicenter study done to verify the performance of this assay. The assay is designed to detect epigenetic modifications in the 3 markers GSTP1, RARβ2 and APC, which are indicative of prostate cancer. A total of 232 men with cancer and 283 without cancer from 18 clinical sites were evaluated by trained operators at central testing laboratories. Study inclusion criteria were age 40 to 75 years, total prostate specific antigen between 2.0 and 10.0 ng/ml, and a digital rectal examination result. All participants signed an informed consent form and underwent transrectal ultrasound guided needle biopsy with 10 or more cores. Assay sensitivity was 60%, specificity was 80% and the informative rate was 97%. Assay predictive accuracy was higher than that of age, digital rectal examination, family history, prostate specific antigen, prior negative biopsy and prostate volume (AUC 0.73 vs 0.52 to 0.66, p <0.038). Risk factors plus the assay improved overall predictive power (AUC 0.79, p = 0.001). A man with a positive prostate cancer methylation result was 7.7 times more likely to have high grade cancer. The prostate cancer methylation assay correlated with positive biopsy and with Gleason score. This assay has the potential to add value to the biopsy decision making process by improving current prostate cancer screening algorithms to more accurately identify men with prostate cancer.

Should we start screening for anal squamous intra-epithelial lesions in HIV-infected homosexual men?

In 1968 Wilson and Jungner published 10 criteria that a screening program should meet before it is introduced (Table 1). Several potentially suitable screening tests have since been rejected by public health authorities because they failed to meet at least one of the 10 criteria. One example is screening for prostate cancer by measuring prostate specific antigen (PSA). Not only was there no disease-specific or overall mortality benefit from PSA screening in a recent systematic review but it generated a large amount of unnecessary, costly and harmful treatment. One of the latest candidate diseases for screening in HIVinfected men who have sex with men (MSM) is anal squamous cell carcinoma, or more precisely, its likely precursor, anal intraepithelial neoplasia (AIN), also known as anal squamous intraepithelial lesions (ASIL). Although they have been revised and adapted by other workers, it is worth consideringWilson and Jungner’s original criteria before deciding to screen for ASIL to prevent anal cancer. Anal cancer is uncommon in the general population with an annual incidence of ~1.5/100 000 but it occurs much more frequently in MSM and even more commonly in MSM with HIV. In the Multicentre AIDS Cohort Study, the incidence of anal cancer was 14/100 000 person-years inMSM, 69/100 000 in HIV-positive MSM and 137/100 000 in HIV-positive MSM in the more recent antiretroviral therapy era. Another cohort study of HIV-positive MSM reported a rate of 75/100 000 person-years. The rate of 14/100 000 in MSM is comparable to rates of cervical cancer before the introduction of cervical screening. Screening for ASIL is hoped to reduce mortality from anal cancer in MSM as it has for cervical cancer. This issue of Sexual Health contains two reports on the acceptability of elements in the screening process for ASIL. They address the sixth of Wilson and Jungner’s criteria, namely that the test for the condition should be acceptable to the population. Botes, Hillman and colleagues report on 291 MSM who collected their own anal smear samples for cytological detection of ASIL. They inserted a moistened polyester swab 3–4 cm and rotated it for at least 1minute. Eighty-six percent found it very or somewhat acceptable and only one respondent regarded it as ‘not acceptable at all’. Mostly minor pain was reported by about a third of the men and bleeding by a sixth. The high acceptability reported here is consistent with that reported for self-collected anal swabs for the diagnosis of sexually transmissible infections, even if the sample-collection for cytology is more vigorous. The same group also examined the acceptability of the next recommended step in the anal cancer screening algorithm, namely high-resolution anoscopy (HRA) and biopsy. Of 105 MSM who had HRA, 70% responded to a questionnaire and 91% of these men scored HRA as either somewhat or very acceptable. Two-thirds of the men reported bleeding and just over half reported minor pain. While the total number offered HRA is not reported and the authors also comment that they did not ask respondents if they would undergo a repeat examination, these figures are very respectable for an inherently uncomfortable examination. They probably reflect well upon the amount of prior counselling given to participants and some respondents in this study did comment on the value of effective communication. Anal cancer screening also fulfils several the other criteria for screening: it is an important health problem (criterion one), and it is probably detectable at an early stage (i.e. AIN, criterion three). And criterion nine has been addressed by a modelling exercise in

Cost-effectiveness of using human papillomavirus 16/18 genotype triage in cervical cancer screening

Objective Testing for human papillomavirus (HPV) 16 and 18 genotypes, which are known to cause approximately 65–70% of invasive cervical cancer cases, may allow clinicians to identify women at highest risk for underlying cervical intraepithelial neoplasia missed by Pap cytology. Our objective was to determine the cost-effectiveness of adding HPV-16 and 18 genotype triage to current cervical cancer screening strategies in the United States. Methods We developed a lifetime Markov model to assess the cost-effectiveness of the following cervical cancer screening algorithms: (1) liquid-based cytology (LBC), (2) LBC + HPV triage, (3) HPV + LBC triage, (4) co-screening, (5) co-screening + HPV genotyping, and (6) HPV only + HPV genotyping. Costs were estimated from a payer perspective in 2007 U.S. dollars. Outcome measures included lifetime risk of cervical cancer, quality-adjusted life years saved (QALYs), and incremental cost-effectiveness ratios (ICERs). Results In our model, the use of HPV genotyping strategies prevented 51–73 deaths per 100,000 women screened compared to screening using LBC followed by HPV triage and 4–26 deaths compared to co-screening with LBC and high-risk HPV. Use of HPV genotyping to triage all high-risk HPV-positive women every three years had an ICER of $34,074 per QALY compared to HPV and LBC co-screening. HPV genotyping with co-screening was the most effective strategy and had an ICER of $33,807 per QALY compared to HPV genotyping for all high-risk HPV-positive women. Conclusion The addition of HPV-16 and -18 genotype triage to HPV and LBC co-screening was a cost-effective screening strategy in the United States.

A study of cervical cancer screening algorithms

To assess the feasibility and accuracy of different cervical cancer screening algorithms suitable for different regions, and promote the prevention and control of cervical cancer in China. Using the data of a cross-sectional comparative trial of multiple techniques to detect cervical intraepithelial neoplasia in Xiangyuan County, Shanxi Province, conducted in 1999, to evaluate the feasibility and accuracy of different cervical cancer screening algorithms. All the women were screened by six screening tests, including liquid based cytology (LBC), fluorescence spectroscopy, visual inspection with 5% acetic acid staining (VIA), colposcopy, self-sampled HPV DNA and clinician-sampled HPV DNA test, and each woman had histopathological diagnosis. Different screening algorithms were developed by combining the screening tests in parallel or in serial, and the performance indexes of the algorithms such as sensitivity, specificity, colposcopy referral rate and receiver operating characteristic (ROC) curve for detecting the high grade lesions (>or= CIN 2) were compared. Among the algorithms combined by LBC and HPV DNA testing, for the combination in parallel (either cytology was greater than ASC-US or HPV positives), its sensitivity was 100%, specificity was 68.6%, and colposcopy referral rate was 34.4%; for the algorithm of LBC as primary screening test, with ASC-US women triage by HPV DNA testing, its sensitivity was 93.0%, specificity was 89.9%, and colposcopy referral rate was 13.7%; for the algorithm of HPV DNA testing as the primary screening test, with HPV positive women triage by LBC, its sensitivity was 91.7%, specificity was 93.0%, and colposcopy referral rate was 10.6%. ROC analysis showed that LBC primary testing followed by HPV triage and HPV primary testing followed by LBC triage were much better than the combination in parallel (P = 0.0003, P = 0.0002). Among the algorithms with LBC or HPV DNA testing solely as primary screening test, the sensitivity, specificity and colposcopy referral rate of LBC were 94.2%, 77.3%, 25.7% and 87.2%, 93.5%, 10.0%, respectively, for cutoff by ASC-US or by LSIL; the sensitivity, specificity and colposcopy referral rate of HPV DNA testing were 97.6%, 84.8%, 18.8% and 83.5%, 85.9%, 17.1%, respectively, for clinician-sampled and self-sampled. Clinician-sampled HPV DNA testing was better than LBC cutoff by ASC-US or self-sampled HPV DNA testing (P = 0.005, P = 0.002). Among the algorithms combined by VIA and HPV DNA testing, the sensitivity, specificity and colposcopy referral rate were 70.9%, 74.3% and 27.6% for VIA alone as primary screening test; the sensitivity, specificity and colposcopy referral rate were 65.9%, 95.2% and 7.4% for HPV as primary screening test with HPV positive women triage by VIA. HPV primary testing followed by VIA triage was better than VIA alone (P = 0.004). Considering the health-resource settings and women's preference, both HPV primary testing followed by LBC triage and LBC primary testing followed by HPV triage are suitable for developed regions, moderately developed regions may choose either LBC or HPV as the screening approach, VIA is a suitable primary screening test in less developed regions, and HPV primary testing followed by VIA triage will be more effective if low cost HPV test is available in the future.

Evaluation of an Array-Based Method for Human Papillomavirus Detection and Genotyping in Comparison with Conventional Methods Used in Cervical Cancer Screening

Cervical cancer is the second-most prevalent cancer in young women around the world. Infection with human papillomavirus (HPV), especially high-risk HPV types (HR-HPV), is necessary for the development of this cancer. HPV-DNA detection is increasingly being used in cervical cancer screening programs, together with the Papanicolau smear test. We evaluated the usefulness of introducing this new array-based HPV genotyping method (i.e., Clinical Arrays Papillomavirus Humano) in the cervical cancer screening algorithm in our center. The results obtained using this method were compared to those obtained by the hybrid capture II high-risk HPV DNA test (HC-II) and Papanicolau in a selected group of 408 women. The array-based assay was performed in women that were HC-II positive or presented cytological alterations. Among 246 array-positive patients, 123 (50%) presented infection with >or=2 types, and HR-HPV types were detected in 206 (83.7%), mainly HPV-16 (24.0%). Up to 132 (33.2%) specimens were classified as ASCUS (for atypical squamous cells of undetermined significance), and only 48 (36.4%) of them were HPV-DNA positive by either assay; however, 78.7% of these cases were caused by HR-HPV types. The agreement between both HPV-DNA detection techniques was fairly good (n = 367). Screening with Papanicolau smear and HC-II tests, followed by HPV detection and genotyping, provided an optimal identification of women at risk for the development of cervical cancer. Furthermore, with the identification of specific genotypes, either in single or multiple infections, a better prediction of disease progression was achieved. The array method also made allowed us to determine the possible contribution of the available vaccines in our setting.

Do We Need a Cancer Screening in Patients with Idiopathic Deep Vein Thrombosis?

To review the literature concerning the need for a cancer screening battery to diagnose a hidden cancer in patients presenting with idiopathic venous thromboembolism (VTE). Data from computerized database programs (Medline, Ovid) was retrieved. A review of the literature regarding studies on cancer screening in patients with idiopathic VTE was performed and our own policy included. Patients with VTE have a higher rate of malignancy which may still be undiagnosed. During follow-up of patients with idiopathic VTE, the incidence of cancer increases and is more likely associated with a worse prognosis. Limited diagnostic work-up in patients with idiopathic VTE allows the diagnosis of a hidden malignancy in about half of the cases with a sensitivity of 48 %. Extensive screening of cancer with idiopathic VTE allows less of a delay and earlier stage at diagnosis with a 93 % sensitivity. However, reduced cancer-related mortality is not statistically significant. A two-fold fatal PE and more than 3-fold fatal bleeding are registered in VTE patients with hidden cancer compared to patients without cancer. The major risk factors for hidden cancer are old age, anemia, idiopathic and bilateral deep vein thrombosis. There is no consensus regarding the benefit of extensive screening in patients presenting with idiopathic VTE. Clear diagnostic work-up guidelines are not yet available. A cost-effective diagnostic algorithm for cancer screening in patients with idiopathic VTE is needed.