Use of primary high-risk human papillomavirus testing for cervical cancer screening: Interim clinical guidance

In 2011, the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology updated screening guidelines for the early detection of cervical cancer and its precursors. Recommended screening strategies were cytology or cotesting (cytology in combination with high-risk HPV (hrHPV) testing). These guidelines also addressed the use of hrHPV testing alone as a primary screening approach, which was not recommended for use at that time. There is now a growing body of evidence for screening with primary hrHPV testing, including a prospective US-based registration study. Thirteen experts including representatives from the Society of Gynecologic Oncology, American Society for Colposcopy and Cervical Pathology, American College of Obstetricians and Gynecologists, American Cancer Society, American Society of Cytopathology, College of American Pathologists, and the American Society for Clinical Pathology, convened to provide interim guidance for primary hrHPV screening. This guidance panel was specifically triggered by an application to the FDA for a currently marketed HPV test to be labeled for the additional indication of primary cervical cancer screening. Guidance was based on literature review and review of data from the FDA registration study, supplemented by expert opinion. This document aims to provide information for health care providers who are interested in primary hrHPV testing and an overview of the potential advantages and disadvantages of this strategy for screening as well as to highlight areas in need of further investigation.

In 2012, clinical guidelines for cervical cancer screening developed by a coalition of experts from several clinical societies such as the American Cancer Society(ACS), American Society for Colposcopy and Cervical Pathology (ASCCP), American Society for Clinical Pathology(ASCP), and the United States Preventative Service Task Force (USPSTF) agreed co-testing with cytology based Papanicolaou smear (Pap smear) and molecular based high-risk Human Papillomavirus (hrHPV) testing were the best methods for detecting early signs of cervical cancer. However, with the future of clinical tests shifting more towards the utilization of molecular diagnostics, there has been a sufficient amount of data published to support that the use of primary hrHPV testing has increased sensitivity over co-testing[1]. With new evidence in favor of molecular testing, in 2017, the USPSTF drafted new guidelines which no longer recommended the use of co-testing, and instead promotes the use of Pap smears every 3 years, or hrHPV testing every 5 years, depending on the women’s age [2]. Roche Molecular Diagnostics played a fundamental role in the changes made to the interim guidelines through developing the cobas 4800 HPV Test System, the first test to gain Food and Drug Administration (FDA) approval for use as primary HPV screening. With this platform, healthcare providers would be able to test for HPV 16 and 18 types responsible for 70% of cervical cancers, as well as 12 other hrHPV types. Implementation of the cobas 4800 in a high volume reference laboratory can improve the workflow and increase the accuracy for triage of screen positive patients. This in turn would reduce the amount of tests performed and result in potential cost savings. For patients, a higher standard of patient care would be achieved through the reduction of unnecessary follow up tests and colposcopy referrals.

To the Editor The new screening guidelines for the “prevention and early detection of cervical cancer” were jointly published by the American Cancer Society, American Society for Colposcopy and Cervical Pathology (ASCCP), and American Society for Clinical Pathology (ASCP) in the American Journal of Clinical Pathology , CA: A Cancer Journal for Clinicians , and the Journal of Lower Genital Tract Disease on March 14, 2012.1 I am asking for more transparency and more explicit disclosure of the judgments about risk and harm thresholds and trade-offs. The guideline panels used the GRADE (Grading Recommendations Assessment, Development, and Evaluation) system to provide a framework for the guideline development process. An integral aspect of the GRADE process is that the grading of the recommendations must be explicit, and that the judgments made by the panels to determine the balance between benefits and risks be explicit and not hidden. I appreciate that there are supplemental materials, including the work of the subgroups that you have made available online.2 I also appreciate that most professionals will not have time to read the entire guideline article, much less the supplemental materials, and that patients and stakeholders will likely not access these materials. The guideline publication explains the difference between strong and weak recommendations, acknowledges that both types were included in the document, but does not stipulate which recommendations were strong and which were …

To the Editor The new screening guidelines for the “prevention and early detection of cervical cancer” were jointly published by the American Cancer Society, American Society for Colposcopy and Cervical Pathology (ASCCP), and American Society for Clinical Pathology (ASCP) in the American Journal of Clinical Pathology , CA: A Cancer Journal for Clinicians , and the Journal of Lower Genital Tract Disease on March 14, 2012.1 I am asking for more transparency and more explicit disclosure of the judgments about risk and harm thresholds and trade-offs. The guideline panels used the GRADE (Grading Recommendations Assessment, Development, and Evaluation) system to provide a framework for the guideline development process. An integral aspect of the GRADE process is that the grading of the recommendations must be explicit, and that the judgments made by the panels to determine the balance between benefits and risks be explicit and not hidden. I appreciate that there are supplemental materials, including the work of the subgroups that you have made available online.2 I also appreciate that most professionals will not have time to read the entire guideline article, much less the supplemental materials, and that patients and stakeholders will likely not access these materials. The guideline publication explains the difference between strong and weak recommendations, acknowledges that both types were included in the document, but does not stipulate which recommendations were strong and which were …

The American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society of Clinical Pathologists have released revised consensus recommendations for cervical cancer screening. These new recommendations integrate molecular testing and include significant changes in screening, particularly in women from 30 to 65 years of age without complications who now may be screened every 5 years by co-testing with cervical cytology and high-risk human papillomavirus testing and women 21-29 years who may be screened with cervical cytology alone every 3 years. The revised recommendations include clarification on when to start and stop screening and management of women who have undergone hysterectomy. They also clarify the management of results of co-testing. The new recommendations achieve the same degree of protection against cervical cancer as previous recommendations. They require less screening and will be much more convenient for our patients. They are a further step away from the days of annual Pap tests, and the decreased requirements for cervical cancer screening pose an exciting opportunity for focusing on many other important health issues during the well woman visit.

A formidable threat to the health of women, cervical carcinoma can be prevented in many cases with adequate screening. The current guidelines for cervical carcinoma screening were created as joint recommendations of the American Cancer Society (ACS), the American Society for Colposcopy and Cervical Pathology (ASCCP) and the American Society for Clinical Pathology (ASCP) in 2012, and later accepted and promoted by the American Congress of Obstetricians and Gynecologists (ACOG). The 2012 recommendations underscore the utility of molecular testing as an adjunct to cytology screening for certain women and provide guidance to clinicians based on different risk-benefit considerations for different ages. This manuscript will review screening techniques and current recommendations for cervical cancer screening and human papilloma virus (HPV) testing, as well as possible future screening strategies.

Recently, practice guideline for the early detection of cervical cancer in Korea has been released in this journal [1].It was developed based on preexisting guidelines generated by the American Society for Colposcopy and Cervical Pathology (ASCCP) [2], the National Comprehensive Cancer Network [3], the United States Preventive Services Task Force [4], and the Institute for Clinical Systems Improvement [5].Coincidentally, updated versions of ASCCP guideline [6] and American Cancer Society (ACS) guideline [7] have been issued around the same time.Therefore, the updated contents of the abovementioned guidelines are not reflected in ours.The essential changes of the 2012 ASCCP guidelines from prior 2006 version are as follows [6]: 1) cytology reported as negative but lacking endocervical cells can be managed without any repeat, 2) cytology reported as unsatisfactory requires repeat even if human papillomavirus (HPV) is negative, 3) For atypical squamous cells of undetermined significance (ASC-US) cytology, immediate colposcopy is not an option.The serial cytology option for ASC-US incorporates cytology at 12 months, and then if negative, cytology every 3 years, 4) ASC-US and HPVnegative results should be followed with co-testing at 3 years rather than 5 years, 5) ASC-US and HPV-negative results are insufficient to allow exit from screening at age 65 years, 6) women aged 21-24 years are managed conservatively.Recently reported rates of cytology results reported as negative but lacking endocervical cells have ranged from 10% to 20% [8].Prior guidelines recommended early repeat cytology [9].A recent meta-analysis found that negative cytology had favorable specificity and negative predictive value despite absent endocervical cell component [10].Given that most cytology is performed using liquid-based media, unsatisfactory cytology results arise mainly from insufficient squamous cells [11].The 2012 ASCCP guidelines recommended repeat cytology in 2 to 4 months for women with an unsatisfactory cytology result.Those two issues regarding specimen adequacy were not included in our guidelines.The management of women with ASC-US has also been

The diagnostic workup of lymphoma continues to evolve rapidly as experience and discovery led to the addition of new clinicopathologic entities and techniques to differentiate them. The optimal clinically effective, efficient, and cost-effective approach to diagnosis that is safe for patients can be elusive, in both community-based and academic practice. Studies suggest that there is variation in practice in both settings. To develop an evidence-based guideline for the preanalytic phase of testing, focusing on specimen requirements for the diagnostic evaluation of lymphoma. The American Society for Clinical Pathology, the College of American Pathologists, and the American Society of Hematology convened a panel of experts in the laboratory workup of lymphoma to develop evidence-based recommendations. The panel conducted a systematic review of literature to address key questions. Using the Grading of Recommendations Assessment, Development, and Evaluation approach, recommendations were derived based on the available evidence, strength of that evidence, and key judgements as defined in the Grading of Recommendations Assessment, Development, and Evaluation Evidence to Decision framework. Thirteen guideline statements were established to optimize specimen selection, ancillary diagnostic testing, and appropriate follow-up for safe and accurate diagnosis of indolent and aggressive lymphoma. Primary diagnosis and classification of lymphoma can be achieved with a variety of specimens. Application of the recommendations can guide decisions on specimen suitability, diagnostic capabilities, and correct use of ancillary testing. Disease prevalence in patient populations, availability of ancillary testing, and diagnostic goals should be incorporated into algorithms tailored to each practice environment.

In 2012, the American Cancer Society, American Society for Clinical Pathology, and American Society for Colposcopy and Cervical Pathology (ASCCP)

Since 2006, when the first human papillomavirus (HPV) vaccine was approved, there has been much progress on the prevention of diseases associated with HPV infection, particularly cervical cancer. A decade...

- To develop evidence-based guideline recommendations through a systematic review of the literature to establish standard molecular biomarker testing of colorectal cancer (CRC) tissues to guide epidermal growth factor receptor (EGFR) therapies and conventional chemotherapy regimens. - The American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology convened an expert panel to develop an evidence-based guideline to establish standard molecular biomarker testing and guide therapies for patients with CRC. A comprehensive literature search that included more than 4,000 articles was conducted. - Twenty-one guideline statements were established. - Evidence supports mutational testing for EGFR signaling pathway genes, since they provide clinically actionable information as negative predictors of benefit to anti-EGFR monoclonal antibody therapies for targeted therapy of CRC. Mutations in several of the biomarkers have clear prognostic value. Laboratory approaches to operationalize CRC molecular testing are presented.

SummaryThe American Society for Clinical Pathology (ASCP), College of American Pathologists (CAP), Association for Molecular Pathology (AMP), and the American Society of Clinical Oncology (ASCO) have been recently strongly recommended the evaluation of mismatch repair status (MMS) as molecular biomarkers in colorectal cancer for a better prognostic stratification of patients. This recommendation is emphasized by the recent evidence of Microsatellite Instability (MSI) as a predictive marker for chemotherapy and immunotherapy.In this scenario, the validation of molecular biomarker testing methods seems to be essential to design the most appropriate tailored therapy and the most suitable care strategy, respectively.In this study, we validated an alternative method based on capillary electrophoresis system label-free PCR (Qiaxcel system) to evaluate the MSI Bethesda Panel. We also parallel the results with a standard approach.Our data showed total concordance with the standard approach, with a highly time-efficient and easy procedure combined with high sensitivity for MSI detection.Alternative capillary electrophoresis based on label-free PCR such as the Qiaxel system is a very sensitive and specific method to detect MSI for the management of patients with colorectal cancer. This procedure is adequate and suitable in diagnostic routine for the evaluation of microsatellite repeats compared to standard procedures.

Involvement of IL-1 and Oncostatin M in Acanthosis Associated With Hypertensive Leg Ulcer

FINAL RULES issued by the federal government, aimed at further regulating cytology laboratories and cytology professionals, appear to be close to the last straw for leaders of their specialty organizations. At this year's joint spring meeting in San Francisco, Calif, the American Society of Clinical Pathologists' (ASCP) president, George D. Lundberg, MD, and the College of American Pathologists' (CAP) president, Loyd R. Wagner, MD, spoke out against the recently promulgated proficiency requirements for those engaged in detecting abnormalities in Papanicolaou smears. A strong backlash is beginning to develop, Lundberg says, among leaders in the professional laboratory community against the dictatorial tactics of the Department of Health and Human Services and the Health Care Financing Administration [HCFA], particularly in relation to its recent issuing of these final rules. While HCFA spokespersons admit that there is no scientific basis for claiming that the type or frequency of proficiency testing that they have

The Preoperative Bleeding Time Test Lacks Clinical Benefit. College of American Pathologists' and American Society of Clinical Pathologists' Position Article