Increasing global accessibility to high-level treatments for cervical cancers.

Human papillomaviruses (HPV)-related gynecological cancers are a major health care issue, and a leading cause of cancer death in low- and middle-income countries (LMIC). In 2020, the World Health Organization launched a program aimed at cervical cancer elimination, by screening and vaccination strategies. Offering the best possible care to women diagnosed with invasive cancer is a complementary objective. Treatment of cervical cancer as per modern standards is complex and multimodal, mainly relying on surgery, external-beam radiotherapy (+/-chemotherapy) and brachytherapy. In parallel with the pivotal role of multidisciplinary discussion, international societies provide guidance to define the most effective and least toxic anti-cancer strategy, homogenize treatment protocols and provide benchmark quality indicators as a basis for accreditation processes. The challenge is to offer the appropriate diagnostic workup and treatment upfront and to avoid non- evidence-based treatment that consumes resources, impairs quality of life (QoL), and compromises oncological outcome. Various strategies may be applied for improving treatment quality: development of surgical mentorship, companion-training programs and international cooperation. The lack of radiotherapy/brachytherapy facilities is a major concern in LMIC. Reinforcing international support in terms of education, training, research and development and technical cooperation with national projects is required to increase access to minimum requirements but also introduce modern techniques, upgrade radiotherapy/brachytherapy services, and expand access to modern systemic treatments. In countries with robust economies, compliance to standards should also be increased. Integrative cancer care and multidisciplinary approaches are needed to tackle the dual challenge of increasing cure rates while minimizing QoL impairment. Appropriate dimensioning of the resources to avoid harmful treatment delays and access to expert referral centers is also a priority.

Morbidity after local excision of the transformation zone for cervical intra-epithelial neoplasia and early cervical cancer.

The awareness that cervical intra-epithelial neoplasia (CIN) treatment increases the risk of preterm birth has led to major changes in clinical practice. Women with CIN have a higher baseline risk of prematurity but local treatment further increases this risk. The risk further increases with increasing cone length and multiplies for repeat excisions; it is unclear whether small cones confer any additional risk to CIN alone. There is no evidence to suggest that fertility is affected by local treatment, although this increases the risk of mid-trimester loss. Caution should prevail when deciding to treat women with CIN of reproductive age. If treatment is offered, this should be conducted effectively to optimise the clearance of disease and minimise the risk of recurrence. Colposcopists should alert women undergoing treatment that this may increase the risk of preterm birth and that they may be offered interventions when pregnant. The cone length should be clearly documented and used as a risk stratifier.

Cervical cancer prevention in transgender men: a review.

There is increased awareness of transgender physical and mental health widely and in academic research. A significant proportion of transgender men will retain their cervix with an increased risk of cervical cancer. In this review of cervical cancer screening among transgender men, we try to estimate how many transgender men still have a cervix, understand to identify challenges and barriers to cervical screening and propose possible solutions. Organised cervical screening programmes need to consider the needs of this population, in particular the provision of HPV self-sampling. TWEETABLE ABSTRACT: Transgender men need access to cervical screening.

Incomplete surgical excision of keratinocyte skin cancers: a systematic review and meta-analysis.

BACKGROUND: Keratinocyte or nonmelanoma skin cancer (NMSC) is the commonest malignancy worldwide. The usual treatment is surgical excision. Current guidelines underestimate incomplete excision rates. OBJECTIVES: We aimed to determine the risk of incomplete excision of NMSCs through a systematic review and meta-analysis of primary clinical studies. METHODS: A PRISMA-compliant systematic review and meta-analysis was performed using methodology proposed by Cochrane (PROSPERO CRD42019157936). A comprehensive search strategy was applied to MEDLINE, Embase, Scopus, CINAHL, EMCare, Cochrane Library and the grey literature (January 2000-27 November 2019). All studies were included except those on Mohs micrographic surgery, frozen section or biopsies. Abstract screening and data extraction were performed in duplicate. Risk of bias was assessed using a tool for prevalence/incidence studies. The primary outcome was the proportion of incomplete surgical excisions. A random-effects model for pooling of binomial data was used. Differences between proportions were assessed by subgroup meta-analysis and meta-regression, which were presented as risk ratios (RRs). RESULTS: Searching identified 3477 records, with 110 studies included, comprising 53 796 patients with 106 832 basal cell carcinomas (BCCs) and 21 569 squamous cell carcinomas (SCCs). The proportion of incomplete excisions for BCC was 11·0% [95% confidence interval (CI) 9·7-12·4] and for SCC 9·4% (95% CI 7·6-11·4). Proportions of incomplete excisions by specialty were: dermatology, BCCs 6·2% and SCCs 4·7%; plastic surgery, BCCs 9·4% and SCCs 8·2%; general practitioners, BCCs 20·4% and SCCs 18·9%. The risk of incomplete excision for general practitioners was four times that of dermatologists for both BCCs (RR 3·9, 95% CI 2·0-7·3) and SCCs (RR 4·8, 95% CI 1·0-22·8). Studies were heterogeneous (I2  = 98%) and at high risk of bias. CONCLUSIONS: The proportion of incomplete excisions is higher than previously reported. Excisions performed by specialists may lower the risk of incomplete excision.

Commercially available molecular tests for human papillomaviruses: a global overview.

BACKGROUND: Molecular tests for detection of human papillomaviruses (HPVs) play a crucial role in the prevention of cervical cancer, including recently announced elimination efforts. HPV testing is a recommended approach for cervical cancer screening of women over 30 and for management of those with precancerous cervical lesions. In addition, they are widely used in epidemiological studies, HPV surveillance and vaccination impact monitoring. OBJECTIVES: The aim was to provide an updated 2020 inventory of commercial molecular HPV tests available on the market. SOURCES: Data were retrieved from internal files, and a detailed search using Medline/Pubmed, Web of Science, Scopus, Google Scholar, Google and Bing, without language or period restrictions, was performed in September 2019 and again in January 2020. CONTENT: We identified 254 distinct commercial HPV tests and at least 425 test variants available on the global market in 2020, which represents a 31% and 235% increase in the number of distinct tests and variants, respectively, compared with the previous inventory performed in 2015. Although the proportion of commercially available HPV tests with at least one peer-reviewed publication has increased over the past decade, 60% of the HPV tests on the global market are still without a single peer-reviewed publication. Furthermore, 82% of tests lack any published analytical and/or clinical evaluation, and over 90% are not evaluated in line with consensus requirements that ensure safe use in clinical settings. IMPLICATIONS: Significant challenges and scope for improvement still exist for both the HPV scientific community and the manufacturers of HPV tests. The latter must put more effort into validating their products, in agreement with standardized procedures, including all steps of HPV testing and various clinical specimens. High throughput capacity and point-of-care HPV tests are needed, both with affordable prices.

Efficacy of strategies to increase participation in cervical cancer screening: GPs offering self-sampling kits for HPV testing versus recommendations to have a pap smear taken - A randomised controlled trial.

Background: Cervical cancer is preventable by early detection and treatment of pre-cancerous lesions. The current screening policy in Belgium (3-yearly cytology on Pap smears) covers 60% of the target population. Offering self-samples by GPs can overcome barriers for women who are currently not screened. Methods: Women aged 25­64 who did not have a Pap smear since three years and consulted a GP practice in a Flemish municipality between November 2014 and April 2015 were allocated in a 1:1 ratio to either the intervention arm where women were given a vaginal self-sampling kit or control arm where women were encouraged to make an appointment for having a Pap smear taken by a clinician. Results: Eighty-eight consenting women were randomised. 35 (78%) out of 45 women in the self-sampling arm participated in screening compared to 22 (51%) out of 43 women in the control arm (p = 0.009). This difference remained significant after adjusting for covariates (age category, education level, time interval since last Pap smear, past Pap smear-taker). Conclusion: GPs offering self-sampling kits resulted in a high participation. Larger trials should confirm this effect and evaluate feasibility of this approach.4. The authors would also like to include the following sentence in the acknowledgement "The laboratory AML (Antwerp, Belgium) is acknowledged for the free HPV testing on the self-samples."

Incidence and mortality from cervical cancer and other malignancies after treatment of cervical intraepithelial neoplasia: a systematic review and meta-analysis of the literature.

BACKGROUND: Although local treatments for cervical intraepithelial neoplasia (CIN) are highly effective, it has been reported that treated women remain at increased risk of cervical and other cancers. Our aim is to explore the risk of developing or dying from cervical cancer and other human papillomavirus (HPV)- and non-HPV-related malignancies after CIN treatment and infer its magnitude compared with the general population. MATERIALS AND METHODS: Design: Systematic review and meta-analysis. Eligibility criteria: Studies with registry-based follow-up reporting cancer incidence or mortality after CIN treatment. DATA SYNTHESIS: Summary effects were estimated using random-effects models. OUTCOMES: Incidence rate of cervical cancer among women treated for CIN (per 100 000 woman-years). Relative risk (RR) of cervical cancer, other HPV-related anogenital tract cancer (vagina, vulva, anus), any cancer, and mortality, for women treated for CIN versus the general population. RESULTS: Twenty-seven studies were eligible. The incidence rate for cervical cancer after CIN treatment was 39 per 100 000 woman-years (95% confidence interval 22-69). The RR of cervical cancer was elevated compared with the general population (3.30, 2.57-4.24; P < 0.001). The RR was higher for women more than 50 years old and remained elevated for at least 20 years after treatment. The RR of vaginal (10.84, 5.58-21.10; P < 0.001), vulvar (3.34, 2.39-4.67; P < 0.001), and anal cancer (5.11, 2.73-9.55; P < 0.001) was also higher. Mortality from cervical/vaginal cancer was elevated, but our estimate was more uncertain (RR 5.04, 0.69-36.94; P = 0.073). CONCLUSIONS: Women treated for CIN have a considerably higher risk to be later diagnosed with cervical and other HPV-related cancers compared with the general population. The higher risk of cervical cancer lasts for at least 20 years after treatment and is higher for women more than 50 years of age. Prolonged follow-up beyond the last screening round may be warranted for previously treated women.

Clinical performance of the HPV-Risk assay on cervical samples in SurePath medium using the VALGENT-4 panel.

BACKGROUND: The VALidation of HPV GENoyping Tests (VALGENT) framework is designed for comparison and clinical validation of HPV assays. OBJECTIVES: To evaluate the accuracy of the HPV-Risk assay within VALGENT-4, relative to clinically validated comparator HPV tests. STUDY DESIGN: The VALGENT-4 panel comprises consecutive SurePath cervical samples from routine screening (n=998), of which 51 had abnormal cytology and 13 women had cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+), enriched with SurePath cervical samples from 297 women with abnormal cytology and 109 CIN2+. HPV-Risk assay was performed on DNA extracted panel samples (n=1,295), blinded to clinical data, cytology results, and results from other HPV assays evaluated in VALGENT-4. All assay results were reported to the central VALGENT coordination institute for data and statistical analysis. HPV prevalence was analysed and accuracy for detection of CIN grade 3 or worse (CIN3+) and CIN2+ were assessed relative to GP5+/6+-PCR-EIA and GP5+/6+-PCR-EIA-LMNX. RESULTS: The sensitivity of the HPV-Risk assay for detection of CIN3+ and CIN2+ was similar to that of GP5+/6+-PCR-EIA (relative sensitivity for CIN3+1.01; 95%CI: 0.97-1.06; pMcN=1.000, and for CIN2+1.01; 95%CI: 0.96-1.06; pMcN=1.000) at significantly higher specificity (relative specificity 1.04; 95%CI: 1.02-1.06; pMcN<0.001). The accuracy of the HPV-Risk assay for CIN3+ and CIN2+ was non-inferior compared to GP5+/6+-PCR- EIA and GP5+/6+-PCR-EIA-LMNX, with all p-values ≤0.002. HPV16/18 genotype agreement between HPV-Risk assay and GP5+/6+-PCR-LMNX was high. CONCLUSIONS: The HPV-Risk assay demonstrated non-inferiority to clinically validated comparator assays on cervical samples in SurePath medium using the VALGENT-4 panel, and is therefore suitable for cervical cancer screening.

Using the VALGENT-3 framework to assess the clinical and analytical performance of the RIATOL qPCR HPV genotyping assay.

BACKGROUND AND OBJECTIVE: The VALGENT framework is developed to assess the clinical performance of HPV tests that offer genotyping capability. Samples from the VALGENT-3 panel are used to identify an optimal viral concentration threshold for the RIATOL qPCR HPV genotyping assay (RIATOL qPCR) to assure non-inferior accuracy to detect high-grade cervical intraepithelial neoplasia (CIN), compared to Qiagen Hybrid Capture 2 (HC2), a standard comparator test validated for cervical cancer screening. STUDY DESIGN: The VALGENT-3 panel comprised 1300 samples from women participating in the Slovenian cervical cancer screening programme, enriched with 300 samples from women with abnormal cytology. In follow- up, 126 women were diagnosed with CIN2+ (defined as diseased) and 1167 women had two consecutive negative Pap smears (defined as non-diseased). All 1600 samples were analyzed with the RIATOL qPCR. Viral concentration was expressed as viral log10 of the number of copies/ml. A zone of viral concentration cut-offs was defined by relative ROC analysis where the sensitivity and specificity were not inferior to HC2. RESULTS: The RIATOL qPCR had a sensitivity and specificity for CIN2+ of 97.6% (CI: 93.2-99.5%) and 85.1% (CI: 82.9-87.1%), respectively, when the analytical cut off was used. At a cut off of 6.5, RIATOL qPCR had a sensitivity of 96.0% (CI: 91.0-98.7%) and a specificity of 89.5% (87.6-91.2%). At optimized cut off, accuracy of the qPCR was non-inferior to the HC2 with a relative sensitivity of 1.00 [CI: 0.95-1.05 (p = 0.006)] and relative specificity of 1.00 [CI: 0.98-1.01 (p = 0.0069)]. CONCLUSIONS: The RIATOL qPCR has a high sensitivity and specificity for the detection of CIN2 + . By using a fixed cut-off based on viral concentration, the test is non-inferior to HC2. HPV tests that provide viral concentration measurements or other quantifiable signals allow flexibility to optimize accuracy required for cervical cancer screening.

Efficacy and safety of prophylactic HPV vaccines. A Cochrane review of randomized trials.

INTRODUCTION: Recently, the evidence on efficacy and safety of prophylactic HPV vaccines derived from randomized trials was published in the Cochrane database of Systematic reviews. A summary of this Cochrane review is presented below. AREAS COVERED: Only trials involving mono-, bi-, and quadrivalent HPV vaccines were included. Trials evaluating the nonavalent vaccine were excluded since women in the control group received the quadrivalent vaccine. Main efficacy outcomes were: histologically confirmed cervical precancer lesions distinguishing those associated with vaccine HPV types and any cervical precancer. Exposure groups were: women aged: 15-26 or 24-45 years being initially negative for high-risk HPV (hrHPV) or negative for the vaccine types and women unselected by HPV status. EXPERT COMMENTARY: All evaluated vaccines offered excellent protection against cervical intraepithelial neoplasia of grade 2 or 3 (CIN2 or CIN3) and adenocarcinoma in situ associated with HPV16/18 infection in young women who were not initially infected with hrHPV or HPV16/18. Vaccine efficacy was lower when all women regardless of HPV DNA status at enrollment were included. In young women, HPV vaccination protected also against any cervical precancer but the magnitude of protection was lower than against HPV16/18 associated cervical precancer. Vaccine efficacy was lower in mid-adult (aged 24-45 years) women. No protection against cervical precancer was found in mid-adult women unselected by HPV DNA status at enrollment. Trials were not empowered to address protection against cervical cancer. Occurrence of severe adverse events or adverse pregnancy outcomes was not significantly higher in recipients of HPV vaccines than in women included in the control arms.

VALHUDES: A protocol for validation of human papillomavirus assays and collection devices for HPV testing on self-samples and urine samples.

BACK GROUND: Systematic reviews have concluded that hrHPV DNA testing using target-amplification tests is as accurate on vaginal self-samples as on clinician-taken specimens for the detection of cervical precancer. However, insufficient evidence is available for specific HPV assay/self-sample device combinations. OBJECTIVES: The VALHUDES protocol is designed as a diagnostic test accuracy study that aims to compare the clinical sensitivity and specificity of particular hrHPV assay(s) on vaginal self-samples and first-void-urine, collected in agreement with standardized protocols, with hrHPV testing on matched clinician-taken samples. STUDY DESIGN: Five hundred enrolled women referred to a colposcopy clinic are invited to collect a first-void urine sample and one or more vaginal self-samples with particular devices before collection of a cervical sample by a clinician. Sample sets are subsequently analysed in a laboratory accredited for HPV testing. Disease verification for all enrolled patients is provided by colposcopy combined with histological assessment of biopsies. RESULTS: A first VALHUDES study has started in Belgium in December 2017 with enrolment from four colposcopy centres. The following assays are foreseen to be evaluated: RealTime High Risk HPV assay (Abbott), cobas-4800 and -6800 (Roche), Onclarity (BD), Xpert HPV (Cepheid) and Anyplex II HPV HR (Seegene). CONCLUSION: Given empirical evidence that the relative accuracy of HPV-testing on self- vs clinician-samples is robust across clinical settings, the VALHUDES protocol offers a framework for validation of HPV assay/self-sample device combinations that can be translated to a primary screening setting.

Accuracy of combinations of visual inspection using acetic acid or lugol iodine to detect cervical precancer: a meta-analysis.

BACKGROUND: Visual inspection of the cervix with acetic acid (VIA) or with Lugol's iodine (VILI) have been evaluated for cervical cancer screening in developing countries. OBJECTIVES: To assess the diagnostic accuracy and clinical utility of visual methods to detect cervical intraepithelial neoplasia grade 2+ (CIN2+) using: (1) VIA alone; (2) VILI alone; (3) co-testing; and (4) VILI as a triage test of a positive VIA result. SEARCH STRATEGY: PubMed, EMBASE, and the Cochrane Library were searched up to May 2016. SELECTION CRITERIA: All reports on the accuracy of VIA and VILI, or combinations of VIA/VILI, to detect CIN2+ were identified. Histology and colposcopy when no biopsy was taken were used as the reference standard. DATA COLLECTION AND ANALYSIS: Selected studies were scored on methodological quality, and sensitivity and specificity were computed. Clinical utility was assessed from the positive predictive value (PPV) and the complement of the negative predictive value (cNPV). MAIN RESULTS: We included 23 studies comprising 101 273 women. The pooled sensitivity and specificity of VILI was 88 and 86%, respectively. VILI was more sensitive, but not less specific, compared with VIA (relative sensitivity = 1.11; 95% confidence interval, 95% CI, 1.06-1.16; relative specificity = 0.98; 95% CI 0.95-1.01). Co-testing was hardly more sensitive, but significantly less specific, than VILI alone. VILI to triage VIA-POSITIVE women was not less sensitive, but more specific, compared with VIA alone (relative sensitivity = 0.98, 95% CI 0.96-1.01; relative specificity = 1.04, 95% CI 1.02-1.05). The average PPVs were low (range 11-16%), whereas the cNPV varied between 0.3% (VILI, co-testing) and 0.6% (triage). CONCLUSIONS: Although imperfect, VILI alone appeared to be the most useful visual screening strategy. TWEETABLE ABSTRACT: VILI alone seems to be the most useful visual screening test for cervical cancer screening.

Evaluation of the Clinical Performance of the HPV-Risk Assay Using the VALGENT-3 Panel.

Human papillomavirus (HPV) testing is increasingly being incorporated into cervical cancer screening. The Validation of HPV Genotyping Tests (VALGENT) is a framework designed to evaluate the clinical performance of various HPV tests relative to that of the validated and accepted comparator test in a formalized and uniform manner. The aim of this study was to evaluate the clinical performance of the HPV-Risk assay with samples from the VALGENT-3 panel and to compare its performance to that of the clinically validated Hybrid Capture 2 assay (HC2). The VALGENT-3 panel comprises 1,300 consecutive samples from women participating in routine cervical cancer screening and is enriched with 300 samples from women with abnormal cytology. DNA was extracted from original ThinPrep PreservCyt medium aliquots, and HPV testing was performed using the HPV-Risk assay by investigators blind to the clinical data. HPV prevalence was analyzed, and the clinical performance of the HPV-Risk assay for the detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) and CIN2 or worse (CIN2+) relative to the performance of HC2 was assessed. The sensitivity of the HPV-Risk assay for the detection of CIN3+ was similar to that of HC2 (relative sensitivity, 1.00; 95% confidence interval [CI], 0.95 to 1.05; P = 1.000), but the specificity of the HPV-Risk assay was significantly higher than that of HC2 (relative specificity, 1.02; 95% CI, 1.01 to 1.04; P < 0.001). For the detection of CIN2+, similar results were obtained, with the relative sensitivity being 0.98 (95% CI, 0.93 to 1.02; P = 0.257) and the relative specificity being 1.02 (95% CI, 1.01 to 1.03; P < 0.001). The performance of the HPV-Risk assay for the detection of CIN3+ and CIN2+ was noninferior to that of HC2, with all P values being ≤0.006. In conclusion, the HPV-Risk assay demonstrated noninferiority to the clinically validated HC2 by the use of samples from the VALGENT-3 panel for test validation and comparison.

Impact of anaesthesia mode on evaluation of LEEP specimen dimensions.

OBJECTIVES: To study the influence of anaesthesia (local by cervical block vs. general or spinal anaesthesia) on height and volume of resection specimens in case of conization treatment for cervical intraepithelial neoplasia (CIN). METHODS: Prospective observational study of all patients who underwent a first treatment by loop electrosurgical excision procedure (LEEP) for CIN. Height of fresh resection specimens was first measured by the operator and then by the pathologist after formaldehyde fixation. Volume of fresh specimens was measured in a measuring cylinder by fluid displacement. RESULTS: One hundred patients were included and 35% of LEEP were performed under local anaesthesia. There was a significant difference in height of specimens depending on anaesthesia mode: after fixation, the average height was 11.2mm in the general or spinal anaesthesia group vs. 8.8mm in the local anaesthesia group (P=0.002). There was also a difference in terms of volume depending on anaesthesia mode: 1.6mL in local anaesthesia group vs. 2.3mm in general and spinal anaesthesia group (P=0.01). CONCLUSIONS: Anaesthesia mode has an impact on height and volume of LEEP specimens. In our experience, local anaesthesia could reduce LEEP specimen height.

Direct comparison of two vaginal self-sampling devices for the detection of human papillomavirus infections.

BACKGROUND AND OBJECTIVES: Two devices for vaginal self-sampling of dry cell material (Evalyn Brush, Rovers Medical Devices; Qvintip, Aprovix) were compared using the Abbott RealTime High Risk HPV test. STUDY DESIGN: Both self-sampling devices (change of order with every patient) including instructions for use and a questionnaire were handed to 146 patients in a colposcopy clinic prior to scheduled colposcopies with collection of cervical reference specimens by gynaecologists using a broom-like device. Matched self-collected and physician collected specimens were transferred to ThinPrep medium and tested for the presence of hr-HPV. Biopsies were taken if indicated by colposcopy. RESULTS: Evaluation of 136 patients with complete data (136/146; 93.2%) showed high agreement of overall hr-HPV detection rates between self-collected and clinician-collected specimens (Evalyn: 91.2% [kappa 0.822]; Qvintip: 89.0% [kappa 0.779]). Colposcopy and histological evaluation revealed 55 women without cervical intraepithelial neoplasia (CIN), 32 CIN1, 34 CIN2, 14 CIN3 and one adenocarcinoma in situ. Hr-HPV testing detected all CIN3+ cases on the clinician-taken or Evalyn self-samples (14/14) and 93% of them on the Qvintip samples (13/14). There was no significant difference regarding the sensitivity for CIN2+ or CIN3+ and specificity of hr-HPV testing on self- vs. clinician samples and on Evalyn vs. Qvintip. Based on signal intensities of ß-globin, the observed DNA concentration with Evalyn samples (mean CN: 22.0; 95%-CI: 21.5-22.6) was found to be significantly higher compared to that of Qvintip samples (mean CN: 23.8; 95%-CI 23.2-24.4), regardless of the order of self-sampling (p<0.0001). Most women considered self-sampling easy and comfortable. Qvintip was considered easier than the Evalyn Brush to understand (p<0.001) and to use (p=0.002). DISCUSSION: This study confirms that hr-HPV testing with a clinically validated PCR-based HPV assay is as accurate on self-samples as on clinician-samples without significant difference between both self-sampling devices.

Clinical and analytical performance of the PapilloCheck HPV-Screening assay using the VALGENT framework.

BACKGROUND: The benefit of HPV testing for cervical cancer screening and disease management has been shown in many recent studies and is part of several new evidence-based guidelines. Assessment of emerging HPV tests in this context is essential, using well-annotated samples, such as those generated via the Validation of Genotyping Tests-HPV (VALGENT) framework. OBJECTIVE: Our aim was to assess the PapilloCheck HPV assay in terms of absolute and relative accuracy for primary cervical cancer screening, using a standard comparator test (GP5+/6+EIA)already validated in randomised trials. STUDY DESIGN: Type-specific HPV prevalence was stratified by age and cytology grade and compared with the luminex typing assay incorporating a GP5+6+ PCR (GP5+/6+ LMNX Assay). Clinical outcomes were compared with GP5+/6+EIA. RESULTS: Prevalence of hrHPV types (high-risk HPV) increased with severity of cytology. The concordance between PapilloCheck and the GP5+/6+ LMNX Assay was excellent when assessed at the qualitative hrHPV presence/absence level also at the type-specific level in the whole population and in women over 30 years of age. Absolute clinical sensitivity and specificity of the PapilloCheck was high and ranged between 95.5% and 98.2% for sensitivity and between 82.7% and 91.6% for specificity, depending on the outcome and population. CONCLUSION: The sensitivity and specificity of this assay for the outcomes of CIN2+ were similar to those of the standard comparator assay, GP5+/6+ EIA.

World Health Organization Guidelines for treatment of cervical intraepithelial neoplasia 2-3 and screen-and-treat strategies to prevent cervical cancer

"BACKGROUND: It is estimated that 1%-2% of women develop cervical intraepithelial neoplasia grade 2-3 (CIN 2-3) annually worldwide. The prevalence among women living with HIV is higher, at 10%. If left untreated, CIN 2-3 can progress to cervical cancer. WHO has previously published guidelines for strategies to screen and treat precancerous cervical lesions and for treatment of histologically confirmed CIN 2-3. METHODS: Guidelines were developed using the WHO Handbook for Guideline Development and the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. A multidisciplinary guideline panel was created. Systematic reviews of randomized controlled trials and observational studies were conducted. Evidence tables and Evidence to Recommendations Tables were prepared and presented to the panel. RESULTS: There are nine recommendations for screen-and-treat strategies to prevent cervical cancer, including the HPV test, cytology, and visual inspection with acetic acid. There are seven for treatment of CIN with cryotherapy, loop electrosurgical excision procedure, and cold knife conization. CONCLUSION: Recommendations have been produced on the basis of the best available evidence. However, high-quality evidence was not available. Such evidence is needed, in particular for screen-and-treat strategies that are relevant to low- and middle-income countries."