Liquid-Based Cytology Compared to Conventional Cytology for Diagnosis of Cervical Intraepithelial Neoplasia: A Single-Center Experience

Abstract Context.—Data on cytologic screening and follow-up disproportionately reflect findings from frequently screened younger women, and data from screened women 50 years and older using newer screening technologies remain limited. Objective.—To better understand the utility of adjunctive high-risk human papillomavirus (hrHPV) testing for disease risk stratification in women 50 years and older with a range of liquid-based cytology, abnormal, squamous cell Papanicolaou test results. Design.—Liquid-based cytology cases interpreted as high-grade squamous intraepithelial lesion (HSIL); low-grade squamous intraepithelial lesion (LSIL); atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H); and atypical squamous cells of undetermined significance (ASC-US) at Magee-Womens Hospital (Pittsburgh, Pennsylvania) were retrospectively identified for a 36-month period between July 1, 2005, and June 30, 2008, from women 50 years and older who also had hrHPV DNA test results. Histopathologic follow-up diagnoses were analyzed. Results.—During the study period, 4855 women 50 years and older had HSIL, LSIL, ASC-H, or ASC-US Papanicolaou test results and hrHPV testing. In 89.3% of HSIL cases, 71.0% of LSIL cases, 38.9% of ASC-H cases, and 14.2% of ASC-US cases, hrHPV test results were positive. The positive predictive value of a positive hrHPV test for histopathologic cervical intraepithelial neoplasia 2/3+ detection was 90.5% with HSIL, 15% with ASC-H, 9.8% with LSIL, and 3.2% with ASC-US. A negative hrHPV test result had a 100% negative predictive value for histopathologic cervical intraepithelial neoplasia 2/3+ in both LSIL and ASC-H cases. Conclusions.—In women 50 years and older, a positive hrHPV test result significantly increased the likelihood of follow-up histopathologic diagnoses of cervical intraepithelial neoplasia 2 /3+ in patients with HSIL, LSIL, and ASC-H Papanicolaou test results compared with women with negative hrHPV test results. No cervical intraepithelial neoplasia 2/3+ diagnoses were documented in women 50 years and older with LSIL or ASC-H Papanicolaou test results and negative hrHPV test results.

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Primary cervical screening with high risk human papillomavirus testing: observational study

BMJ ◽

10.1136/bmj.l240 ◽

2019 ◽

pp. l240 ◽

Cited By ~ 33

Author(s):

Matejka Rebolj ◽

Janet Rimmer ◽

Karin Denton ◽

John Tidy ◽

Christopher Mathews ◽

...

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

High Risk ◽

Observational Study ◽

Cervical Intraepithelial Neoplasia ◽

Cervical Screening ◽

Intraepithelial Neoplasia ◽

Cervical Intraepithelial Neoplasia Grade ◽

Liquid Based Cytology ◽

Grade 3

AbstractObjectiveTo provide the first report on the main outcomes from the prevalence and incidence rounds of a large pilot of routine primary high risk human papillomavirus (hrHPV) testing in England, compared with contemporaneous primary liquid based cytology screening.DesignObservational study.SettingThe English Cervical Screening Programme.Participants578 547 women undergoing cervical screening in primary care between May 2013 and December 2014, with follow-up until May 2017; 183 970 (32%) were screened with hrHPV testing.InterventionsRoutine cervical screening with hrHPV testing with liquid based cytology triage and two early recalls for women who were hrHPV positive and cytology negative, following the national screening age and interval recommendations.Main outcome measuresFrequency of referral for a colposcopy; adherence to early recall; and relative detection of cervical intraepithelial neoplasia grade 2 or worse from hrHPV testing compared with liquid based cytology in two consecutive screening rounds.ResultsBaseline hrHPV testing and early recall required approximately 80% more colposcopies, (adjusted odds ratio 1.77, 95% confidence interval 1.73 to 1.82), but detected substantially more cervical intraepithelial neoplasia than liquid based cytology (1.49 for cervical intraepithelial neoplasia grade 2 or worse, 1.43 to 1.55; 1.44 for cervical intraepithelial neoplasia grade 3 or worse, 1.36 to 1.51) and for cervical cancer (1.27, 0.99 to 1.63). Attendance at early recall and colposcopy referral were 80% and 95%, respectively. At the incidence screen, the 33 506 women screened with hrHPV testing had substantially less cervical intraepithelial neoplasia grade 3 or worse than the 77 017 women screened with liquid based cytology (0.14, 0.09 to 0.23).ConclusionsIn England, routine primary hrHPV screening increased the detection of cervical intraepithelial neoplasia grade 3 or worse and cervical cancer by approximately 40% and 30%, respectively, compared with liquid based cytology. The very low incidence of cervical intraepithelial neoplasia grade 3 or worse after three years supports extending the screening interval.

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Evaluation of DNA extraction protocols from liquid-based cytology specimens for studying cervical microbiota

10.1101/2020.01.27.921619 ◽

2020 ◽

Author(s):

Takeo Shibata ◽

Mayumi Nakagawa ◽

Hannah N. Coleman ◽

Sarah M. Owens ◽

William W. Greenfield ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Screening ◽

Cervical Intraepithelial Neoplasia ◽

Dna Extraction ◽

Cervical Cancer Screening ◽

Intraepithelial Neoplasia ◽

Extraction Protocol ◽

Hpv Genotyping ◽

Liquid Based Cytology

AbstractBackgroundCervical microbiota (CM) are considered an important factor affecting the progression of cervical intraepithelial neoplasia (CIN) and are implicated in the persistence of human papillomavirus (HPV). Collection of liquid-based cytology (LBC) samples is routine for cervical cancer screening and HPV genotyping, and can be used for long-term cytological biobanking. Herein, we investigate the feasibility of leveraging LBC specimens for use in CM surveys by amplicon sequencing. As methodological differences in DNA extraction protocols can potentially bias the composition of microbiota, we set out to determine the performance of four commonly used DNA extraction kits (ZymoBIOMICS DNA Miniprep Kit; QIAamp PowerFecal Pro DNA Kit; QIAamp DNA Mini Kit; and IndiSpin Pathogen Kit) and their ability to capture the diversity of CM from LBC specimens.ResultsLBC specimens from 20 patients (stored for 716 ± 105 days) with cervical intraepithelial neoplasia (CIN) 2/3 or suspected CIN2/3 were each aliquoted for the four kits. We observed that, regardless of the extraction protocol used, all kits provided equivalent accessibility to the cervical microbiome, with some minor differences. For example, the ZymoBIOMICS kit appeared to differentially increase access of several microbiota compared to the other kits. Potential kit contaminants were observed as well. Approximately 80% microbial genera were shared among all DNA extraction protocols. The variance of microbial composition per individual was larger than that of the DNA extraction protocol used. We also observed that HPV16 infection was significantly associated with community types that were not dominated by Lactobacillus iners.ConclusionsCollection of LBC specimens is routine for cervical cancer screening and HPV genotyping, and can be used for long-term cytological biobanking. We demonstrated that LBC samples, which had been under prolonged storage prior to DNA extraction, were able to provide a robust assessment of the CM and its relationship to HPV status, regardless of the extraction kit used. Being able to retroactively access the CM from biobanked LBC samples, will allow researchers to better interrogate historical interactions between the CM and its relationship to CIN and HPV. This alone has the potential to bring CM research one-step closer to the clinical practice.

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