Detection Of High-grade Cervical Lesions Research Articles

HR-HPV E6/E7 mRNA test for the detection of high-grade cervical lesions among women with gynecology complaints in northwest Ethiopia

HR-HPV E6/E7 mRNA test for the detection of high-grade cervical lesions among women with gynecology complaints in northwest Ethiopia

Optimizing biopsy procedures during colposcopy and detection of high-grade cervical lesions

Objective: To investigate the value of biopsies on diagnosing cervical intraepithelial neoplasia of grade 2 or worse (CIN Ⅱ+), and optimize biopsy procedures of risk-based colposcopy practice. Methods: A prospective study was performed on 346 women referred to colposcopy following abnormal cervical cancer screening results at the First Affiliated Hospital of Nanjing Medical University, from April 2017 to December 2019. Up to 4 cervical biopsies were taken during colposcopy and each biopsy specimen was evaluated separately in histology. CIN Ⅱ+ identified by any biopsy was the reference standard of disease used to evaluate the diagnostic value of targeted biopsy and random biopsy, and to quantify the improved detection of CIN Ⅱ+ by taking multiple biopsies. Cervical cytology, HPV genotyping, and colposcopic impression were used to establish different risk strata to select various multiple biopsies procedures during colposcopy to improve accuracy and efficiency of CIN Ⅱ+ detection. Results: In total 346 women, 190 (54.9%, 190/346) cases of them were diagnosed as CIN Ⅱ+. (1) In total 346 women, 96.8% (184/190) CIN Ⅱ+ were detected by targeted biopsies, 27.9% (53/190) CIN Ⅱ+ were detected in biopsies targeted grade 1 abnormal colposcopic findings (G1) on the cervix, and 68.9% (131/190) CIN Ⅱ+ were detected in biopsies targetrd grade 2 abnormal colposcopic findings (G2) on the cervix. Colposcopy had a sensitivity of 68.9% when the biopsy threshold was G2, sensitivity increased to 96.8% when the biopsy threshold was defined to be G1. Among women with G1, adding 2 targeted biopsies to the first biopsy were sufficient to detect all CIN Ⅱ+, among women with G2, adding 1 targeted biopsy was sufficient. (2) Among 270 women, random biopsies targeted normal colposcopic findings on the cervix were performed in addition to targeted biopsies and in total 3.2% (6/190) additional CIN Ⅱ+ were detected. As the number of cervical quadrants involved by abnormal colposcopic images increased, random biopsy detected fewer CIN Ⅱ+ that would have otherwise been missed by targeted biopsies (P=0.010). (3) Women with atypical squamous cells,cannot exclude high grade squamous intraepithelial lesion (ASC-H), high grade squamous intraepithelial lesion (HSIL) or atypical glandular cell (AGC) referral cytology, HPV 16-positive, G2 were more likely to have CIN Ⅱ+(P<0.01); for those meeting only one category, the yield of CIN Ⅱ+ increased from 34.0% for one biopsy to 51.0% for two biopsies, the absolute increase in CIN Ⅱ+ yield increased from the first to the second biopsy was 17.0%, two biopsies were sufficient to detect all CIN Ⅱ+; for those meeting at least two categories, the yield of CIN Ⅱ+ increased from 90.7% for one biopsy to 92.6% for two biopsies, the absolute increase in CIN Ⅱ+ yield increased from the first to the second biopsy was 1.9%, two biopsies were sufficient to detect all CIN Ⅱ+; for those not meeting any category, the yield of CIN Ⅱ+ increased from 8.8% for one biopsy to 17.6% for two biopsies, to 23.5% for three biopsies, the absolute increase in CIN Ⅱ+ yield increased from the first to the second biopsy, from the second to the third biopsy was 8.8%, 5.9%, three biopsies were sufficient to detect all CIN Ⅱ+. Conclusions: Performing multiple targeted biopsies could improve efficiency of CIN Ⅱ+ detection. Adding random biopsies to multiple targeted biopsies showed very limited additional benefit for detection of CIN Ⅱ+. The biopsy procedures undertaken during the colposcopy visit could be modified based on various colposcopic impressions and reasons for referral.

Prevalence of High-Risk Human Papillomavirus Types Among Women Screened for Cervical Cancer in Yazd, Iran, and Comparison of Cytology, Histology, and Colposcopy Results

Background: Human Papillomavirus (HPV) is a DNA virus with more than 100 genotypes, at least 12 of which are high-risk and associated with high-grade cervical lesions. Data on the prevalence of high-risk HPV genotypes among women are not yet available for the total regions of Iran. Objectives: The present study aimed to determine the prevalence of high-risk HPV types among women screened for cervical carcinoma in Yazd and compare the cytology, histology, and colposcopy results. Methods: In this cross-sectional study, 402 women referring to gynecology clinics of Shahid Sadoughi University of Medical Sciences, Yazd, Iran, were selected. The Pap smear and HPV typing were performed on cervical samples. The high-risk HPV types were detected by the polymerase chain reaction (PCR)-based reverse blot hybridization assay. Colposcopy was carried out on patients with high-risk HPV types, and biopsies were taken for histological examination. Results: Among 402 women screened by HPV-PCR, 32 (7.97%) women were positive for high-risk HPV types. Human papillomavirus 16 and HPV18 were the most frequent genotypes (46.9%). The cytology, histology, and colposcopy results were abnormal in 56.2%, 29.1%, and 71.9% of patients, respectively. Pap smear had 100% sensitivity and 58.3% specificity for the detection of high-grade cervical lesions, while these values for colposcopy were 75% and 87.5%, respectively. Conclusions: The frequency of high-risk HPV types was relatively low among women living in Yazd than in those from other provinces of Iran. A significant percentage of patients with HPV had normal cervical cytology and histology. Therefore, HPV typing is recommended to decrease the development of cervical cancer. Colposcopy had acceptable sensitivity and specificity for the detection of high-grade cervical lesions.

Plasma expression of miRNA-21, \u2212\u2009214, \u221234a, and -200a in patients with persistent HPV infection and cervical lesions

BackgroundTo examine differences in the plasma levels of miRNA-21, − 214, −34a, and -200a in patients with persistent high-risk human papillomavirus (hr-HPV) infection or with cervical lesions of different grades.MethodsVenous blood was collected from 232 individuals to measure the plasma expression levels of miRNA-21, − 214, −34a, and -200a. The subjects included normal controls and patients with persistent hr-HPV infection, CIN1, CIN2, CIN3, or cervical cancer (n = 42, 31, 19, 54, 71, and 15 patients, respectively). Cervical conization specimens were collected from all the women. To ensure the accuracy of histopathology, three consecutive tissue sections with an identical diagnosis were selected, and dissection samples were taken from them for miRNA detection. Eligible cases met the inclusion criteria based on sample observation using the middle slice of sandwich tissue sections from the pathological tissue in accordance with the diagnosis of CIN1, CIN2 and CIN3 in 8, 29, and 26 cases, respectively. The miRNA-21, − 214, −34a, and -200a expression levels in the paraffin-embedded tissue samples were determined. The percentage of patients with a CIN2+ diagnosis at 30–49 years old was significantly different from that of those diagnosed with CIN1. The incidence of CIN2+ patients exposed to passive smoking was significantly different from that of CIN1- patients. The percentage of CIN2+ patients with three pregnancies was significantly different from that of those with CIN1, and the percentage of CIN2+ subjects with ≥4 pregnancies was significantly different from that of CIN1- patients. The number of CIN2+ patients with two or more induced abortions was significantly different from that of patients with CIN1. The percentage of CIN2+ patients who underwent a caesarean section was significantly different from that of patients with CIN. The percentage of CIN2+ patients with first-degree relatives with cancer was significantly different from that of those with CIN1. Among CIN2+ patients, the percentage with a first sexual encounter at ≤20 years old was significantly different from that of those with CIN1. The percentage of CIN2+ patients with ≥2 sexual partners was significantly different from that of CIN1- patients.ResultsThe plasma miRNA-214, −34a, and -200a expression levels were decreased in patients with more severe cervical lesions. Plasma miRNA levels in CIN1- patients were significantly different from those in CIN2+ patients. The kappa values for miRNA-21, − 214, −34a and -200a in tissue versus plasma were 0.7122, 0.9998, 0.8986 and 0.7458, respectively. The sensitivity of each biomarker for detecting CIN2 was calculated, and ROC curves of the four miRNA biomarkers were drawn. The AUC of the four plasma miRNAs was greater than 0.5, with the AUC of miRNA-21 being the largest at 0.703. The plasma miRNA expression levels exhibited at least one tie between CIN1 and CIN2. The AUCs for miRNA-21, −34a, −200a and − 214 were 0.613, 0.508, 0.615 and 0.505, respectively.ConclusionsChanges in plasma miRNA-21, − 214, −34a and -200a levels were associated with cervical lesion severity. The plasma miRNA levels in CIN1- subjects were significantly different from those in CIN2+ subjects. This analysis may help in detection of high-grade cervical lesions.

P16/Ki67 dual staining improves the detection specificity of high-grade cervical lesions.

The goal of this study was to analyze the specificity of p16/Ki67 dual staining in the detection of high-grade cervical lesions. A total of 223 patients with an average age of 39 years old were enrolled in this study. All samples were analyzed by p16/Ki67 immunocytochemical dual staining, liquid-based cytology and high-risk human papillomavirus (HR-HPV) test. Diagnosis of each patient was verified by histopathological test. The specificity of p16/Ki67 dual staining was 68.33%, which was significantly higher than that of cytology (38.33%) and HR-HPV test (21.67%) (P < 0.05) for CIN2+ detection. p16/Ki67 dual staining had similar sensitivity with HR-HPV test for CIN2+ detection (90.18% vs 93.87%, P = 0.286). In atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) cases, the specificity of p16/Ki67 dual staining was significantly higher than that of HPV test (66.67% vs 3.70%, P < 0.05) and its sensitivity was similar to that of HPV test for CIN2+ detection. The sensitivity and specificity of dual staining for CIN2+ detection in HR-HPV positive women were 90.85% and 70.21%, respectively, which were higher than those of cytology (83.01% and 42.55%) and HPV16/18 test (70.59% and 44.68%). p16/Ki67 dual staining could improve the specificity of high-grade cervical lesions detection and have similar sensitivity to HPV test for CIN2+ detection. When triaging women with ASC-US or LSIL liquid-based cytology, compared with positive HR-HPV, the specificity of CIN2+ lesion detection was increased by p16/Ki67 dual staining. p16/Ki67 dual staining could reduce colposcopy referrals and avoid excessive diagnosis and treatment.

Assessment of viral methylation levels for high risk HPV types by newly designed consensus primers PCR and pyrosequencing.

BackgroundMeasuring viral DNA methylation in human papillomavirus (HPV) infected women showed promise for accurate detection of high-grade cervical lesions and cancer. Methylation status has been widely investigated for HPV16, sporadically for other HPV types.MethodsObjective of this methodological study was to set up molecular methods to test the methylation levels in the twelve oncogenic HPV types by pyrosequencing, minimizing the number of HPV type-specific PCR protocols. Target CpGs were selected on the HPV L1 (two regions, L1 I and L1 II) and L2 genes.Study samples included DNA stored at Turin, Italy, purified by cervical cells collected in Standard Transport Medium or PreservCyt from women who participated in two studies (N = 126 and 140) nested within the regional organized screening programme.PCR consensus primers were designed by PyroMark Assay Design software to be suitable for amplification of many different oncogenic HPV types.ResultsGeneration of consensus primers was successful for L1 I and II regions, unsuccessful for L2 region, for which HPV type-specific primers remained necessary. The difference between replicated tests on the same sample was ≤4% in 88%, 77% and 91% of cases when targeting the L1 I, L1 II and L2 regions, respectively. The corresponding intra-class correlation coefficients (ICC) were 0.94, 0.87 and 0.97 respectively. When comparing methylation measures based on consensus and type-specific primers, ICC was 0.97 for the L1 I region and 0.99 the for L1 II region.ConclusionsThe proposed protocols, applying consensus primers suitable to amplify the oncogenic HPV types and minimize the number of PCR reactions, represent a promising tool to quantify viral methylation in women positive for any high risk HPV type.ImpactPotential application of these methylation protocols in screening settings can be explored to identify women with high probability of progression to high grade lesions.

Do Infection Patterns of Human Papillomavirus Affect the Cytologic Detection of High-Grade Cervical Lesions on Papanicolaou Tests?

- Persistent infection with high-risk human papillomavirus (hrHPV) is the major cause of cervical cancer. The effect of HPV infection patterns on cytologic detection of cervical lesions is unknown. - To determine the effect of HPV infection patterns on the sensitivity of cytologic detection of high-grade cervical lesions. - Papanicolaou tests from 257 women with biopsy-confirmed, high-grade squamous intraepithelial lesions were analyzed with respect to HPV infection patterns. - Among 257 biopsy-confirmed, high-grade squamous intraepithelial lesion cases, the preceding cytology showed 20 cases (8%) were benign; 166 cases (65%) were low-grade cervical lesions, including atypical squamous cell of undetermined significance and low-grade squamous intraepithelial lesions; and 71 cases (28%) were high-grade cervical lesions, including atypical squamous cells cannot rule out high-grade squamous intraepithelial lesion (atypical squamous cell-high), atypical glandular cells, and high-grade squamous intraepithelial lesions. In 236 cases tested for HPV, those exhibiting low-grade cervical lesions on cytology were often associated with coinfections of mixed hrHPV genotypes (31 of 40; 78%) or non-16/18 hrHPV (75/103; 73%), compared with single-genotype infections of HPV-16 (33 of 62; 53%) or HPV-18 (2 of 6; 33%) ( P = .001). In contrast, high-grade cervical lesion cytomorphology tended to associate with the single-genotype infection of HPV-16 (20 of 62; 32%) or HPV-18 (3 of 6; 50%), compared with non-16/18 hrHPV (25 of 103; 24%) or multigenotype infection (8 of 40; 20%) ( P = .01). - Our findings suggest that multigenotypic or non-16/18 hrHPV infections often produce deceptive lower-grade cytomorphology, which could result in underdiagnosis and delay of treatment. The HPV infection patterns may offer unrecognized benefit beyond HPV genotyping and should be considered during clinical risk evaluation of women with lower-grade cytology.

Can Dynamic Spectral Imaging System colposcopy replace conventional colposcopy in the detection of high-grade cervical lesions?

The sensitivity of conventional colposcopy for the detection of high-grade cervical lesions (cervical intraepithelial neoplasia stage 2 or above; CIN2+) is poor. We aimed to investigate if a Dynamic Spectral Imaging System (DySIS) can enhance or replace conventional colposcopy in clinical practice. From 3 December 2013 to 29 January 2014 a total of 239 women were included. All women were referred to the Department of Obstetrics and Gynecology, Aarhus, Denmark because of an abnormal cytology result. Every woman had three to five cervical punch biopsies taken; two biopsies were taken following DySIS recommendations. Subsequent biopsies were taken following the clinician's assessment or randomly. DySIS allowed detection of five CIN2+ cases (7.4%) that would not have been detected otherwise, but it failed to detect 46 of CIN2+ cases (67.6%). The sensitivity and specificity of DySIS for detecting CIN2+ was 32.4 and 83.0%, respectively. DySIS colposcopy seemed inferior to conventional colposcopy in detecting high-grade lesions and cannot replace conventional colposcopy with random biopsies.

Comparison of the performance of the NucliSENS EasyQ HPV E6/E7 mRNA assay and HPV DNA chip for testing squamous cell lesions of the uterine cervix

This study aims to evaluate the clinical performance of the NucliSENS EasyQ assay and compare it with HPV DNA genotyping for the detection of high-grade squamous intraepithelial lesions (HSIL) and cancer in a Korean population. In 188 total thin prep samples, the remaining fluid after cytology slide preparation was tested with Goodgene HPV DNA chips and the NucliSENS EasyQ HPV E6/E7 messenger RNA (mRNA) assay. The sensitivity and specificity of each test were calculated with HSIL and squamous cell carcinoma (SCC) as the disease endpoint. Out of the 188 samples, 139 (74%) were positive for DNA of 14 HPV types, while 57 (30%) cases were positive for E6/E7 mRNA. The DNA test was positive in cytology cases of SCC, HSIL, and atypical squamous cell. The mRNA test yielded results of 75%, 74%, 60%, 56%, and 29% positivity in abnormal cytology cases of SCC, HSIL, atypical squamous cells – cannot exclude HSIL, atypical squamous cells of undetermined significance, and low-grade squamous intraepithelial lesion, respectively. In normal cytology cases, the positivity rates were 9% and 53% for the mRNA and DNA tests, respectively. For detection of HSIL and SCC, the sensitivity of the mRNA test was 74.36% and that of the DNA test was 100%, while the specificities of the tests were 85% and 40.83%, respectively. These findings suggest that the HPV E6/E7 mRNA assay can overcome the shortcoming of low specificity of DNA assays for clinical detection of high-grade cervical lesions and malignancies.

Genomic amplification patterns of human telomerase RNA gene and C-MYC in liquid-based cytological specimens used for the detection of high-grade cervical intraepithelial neoplasia

BackgroundThe amplification of oncogenes initiated by high-risk human papillomavirus (HPV) infection is an early event in cervical carcinogenesis and can be used for cervical lesion diagnosis. We measured the genomic amplification rates and the patterns of human telomerase RNA gene (TERC) and C-MYC in the liquid-based cytological specimens to evaluate the diagnostic characteristics for the detection of high-grade cervical lesions.MethodsTwo hundred and forty-three residual cytological specimens were obtained from outpatients aged 25 to 64 years at Qilu Hospital, Shandong University. The specimens were evaluated by fluorescence in situ hybridization (FISH) using chromosome probes to TERC (3q26) and C-MYC (8q24). All of the patients underwent colposcopic examination and histological evaluation. A Chi-square test was used for categorical data analysis.ResultsIn the normal, cervical intraepithelial neoplasia grade 1 (CIN1), grade 2 (CIN2), grade 3 (CIN3) and squamous cervical cancer (SCC) cases, the TERC positive rates were 9.2%, 17.2%, 76.2%, 100.0% and 100.0%, respectively; the C-MYC positive rates were 20.7%, 31.0%, 71.4%, 81.8% and 100.0%, respectively. The TERC and C-MYC positive rates were higher in the CIN2+ (CIN2, CIN3 and SCC) cases than in the normal and CIN1 cases (p < 0.01). Compared with cytological analysis, the TERC test showed higher sensitivity (90.0% vs. 84.0%) and higher specificity (89.6% vs. 64.3%). The C-MYC test showed lower sensitivity (80.0% vs. 84.0%) and higher specificity (77.7% vs. 64.3%). Using a cut-off value of 5% or more aberrant cells, the TERC test showed the highest combination of sensitivity and specificity. The CIN2+ group showed more high-level TERC gene copy number (GCN) cells than did the normal/CIN1 group (p < 0.05). For C-MYC, no significant difference between the two histological categories was detected (p > 0.05).ConclusionsThe TERC test is highly sensitive and is therefore suitable for cervical cancer screening. The C-MYC test is not suitable for cancer screening because of its lower sensitivity. The amplification patterns of TERC become more diverse and complex as the severity of cervical diseases increases, whereas for C-MYC, the amplification patterns are similar between the normal/CIN1 and CIN2+ groups.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1308004512669913.

Human papillomavirus testing for the detection of high-grade cervical intraepithelial neoplasia and cancer: final results of the POBASCAM randomised controlled trial

Human papillomavirus (HPV) testing is more sensitive for the detection of high-grade cervical lesions than is cytology, but detection of HPV by DNA screening in two screening rounds 5 years apart has not been assessed. The aim of this study was to assess whether HPV DNA testing in the first screen decreases detection of cervical intraepithelial neoplasia (CIN) grade 3 or worse, CIN grade 2 or worse, and cervical cancer in the second screening. In this randomised trial, women aged 29-56 years participating in the cervical screening programme in the Netherlands were randomly assigned to receive HPV DNA (GP5+/6+-PCR method) and cytology co-testing or cytology testing alone, from January, 1999, to September, 2002. Randomisation (in a 1:1 ratio) was done with computer-generated random numbers after the cervical specimen had been taken. At the second screening 5 years later, HPV DNA and cytology co-testing was done in both groups; researchers were masked to the patient's assignment. The primary endpoint was the number of CIN grade 3 or worse detected. Analysis was done by intention to screen. The trial is now finished and is registered, number ISRCTN20781131. 22,420 women were randomly assigned to the intervention group and 22 518 to the control group; 19 999 in the intervention group and 20,106 in the control group were eligible for analysis at the first screen. At the second screen, 19 579 women in the intervention group and 19,731 in the control group were eligible, of whom 16,750 and 16,743, respectively, attended the second screen. In the second round, CIN grade 3 or worse was less common in the intervention group than in the control group (88 of 19 579 in the intervention group vs 122 of 19,731 in the control group; relative risk 0·73, 95% CI 0·55-0·96; p=0·023). Cervical cancer was also less common in the intervention group than in the control group (four of 19 579 in the intervention group vs 14 of 19,731; 0·29, 0·10-0·87; p=0·031). In the baseline round, detection of CIN grade 3 or worse did not differ significantly between groups (171 of 19 999 vs 150 of 20,106; 1·15, 0·92-1·43; p=0·239) but was significantly more common in women with normal cytology (34 of 19,286 vs 12 of 19,373; 2·85, 1·47-5·49; p=0·001). Furthermore, significantly more cases of CIN grade 2 or worse were detected in the intervention group than in the control group (267 of 19 999 vs 215 of 20,106; 1·25, 1·05-1·50; p=0·015). In the second screen, fewer HPV16-positive CIN grade 3 or worse were detected in the intervention group than in the control group (17 of 9481 vs 35 of 9354; 0·48, 0·27-0·85; p=0·012); detection of non-HPV16-positive CIN grade 3 or worse did not differ between groups (25 of 9481 vs 25 of 9354; 0·99, 0·57-1·72; p=1·00). The cumulative detection of CIN grade 3 or worse and CIN grade 2 or worse did not differ significantly between study arms, neither for the whole study group (CIN grade 3 or worse: 259 of 19 999 vs 272 of 20,106; 0·96, 0·81-1·14, p=0·631; CIN grade 2 or worse: 427 of 19 999 vs 399 of 20,106; 1·08, 0·94-1·24; p=0·292), nor for subgroups of women invited for the first time (CIN grade 3 or worse in women aged 29-33 years: 102 of 3139 vs 105 of 3128; 0·97, 0·74-1·27; CIN grade 2 or worse in women aged 29-33 years: 153 of 3139 vs 151 of 3128; 1·01, 0·81-1·26; CIN grade 3 or worse in women aged 34-56 years: 157 of 16,860 vs 167 of 16 978; 0·95, 0·76-1·18; CIN grade 2 or worse in women aged 34-56 years: 274 of 16,860 vs 248 of 16 978; 1·11, 0·94-1·32). Implementation of HPV DNA testing in cervical screening leads to earlier detection of clinically relevant CIN grade 2 or worse, which when adequately treated, improves protection against CIN grade 3 or worse and cervical cancer. Early detection of high-grade cervical legions caused by HPV16 was a major component of this benefit. Our results lend support to the use of HPV DNA testing for all women aged 29 years and older. Zorg Onderzoek Nederland (Netherlands Organisation for Health Research and Development).

High-Risk HPV DNA Testing and HPV-16/18 Genotyping

There are currently 2 tests approved for clinical use that nonspecifically detect the presence of multiple oncogenic or high-risk human papillomavirus (HPV) types. One HPV genotyping test is also available for use that specifically detects the presence of high-risk HPV types 16 and 18. The purpose of this review was to evaluate the clinical performance of these HPV DNA tests and the utility of the tests within current screening recommendations. The sensitivity and specificity of currently available HPV DNA tests to detect the presence of precancerous high-grade cervical lesions are reviewed. Appropriate test usage is discussed in the context of the natural history of HPV infection. Molecular testing for the presence of high-risk HPV is more sensitive but less specific than cytologic testing for the detection of high-grade cervical lesions. Current patient management guidelines recommend the use of high-risk HPV DNA testing to triage women 21 years or older with equivocal cytology results and in conjunction with cytology for cervical screening in women 30 years or older. The HPV-16/18 genotyping test may be used in women 30 years or older with negative cytology and positive high-risk HPV DNA test results to determine the need for colposcopy. Although infection with high-risk HPV is highly prevalent in adult females, most infections are transient and do not require intervention. Clinical application of appropriate age-adjusted use of HPV DNA testing and its use in conjunction with atypical squamous cells of undetermined significance cytology will avoid unnecessary follow-up procedures.

Clinical importance of “low-grade squamous intraepithelial lesion, cannot exclude high-grade squamous intraepithelial lesion (LSIL-H)” terminology for cervical smears: 5-year analysis of the positive predictive value of LSIL-H compared with ASC-H, LSIL, and HSIL in the detection of high-grade cervical lesions with a review of the literature

ObjectiveWe compared follow-up biopsy findings and positive predictive values (PPVs) for cervical intraepithelial neoplasia 2 or worse (CIN 2+) in cases that were cytologically interpreted as low-grade squamous intraepithelial lesions (LSIL); high-grade squamous intraepithelial lesions (HSIL); LSIL, cannot exclude HSIL (LSIL-H); and atypical squamous cells, cannot exclude HSIL (ASC-H) during a 5-year period to evaluate the clinical significance of LSIL-H as a distinct cytological category. MethodsAll Pap tests with a diagnosis of LSIL-H, ASC-H, LSIL, and HSIL (January 1, 2004–July 20, 2009) were retrieved from our computer database. PPVs of cytological diagnostic categories for detecting CIN 2+ were compared. ResultsOf all Pap tests (n=163,315), 1713 cases that had histological confirmation were included in the study. The LSIL-H diagnosis represented only 0.23% (n=387) of all Pap tests and 9.3% of all cytological SILs (n=4119). LSIL alone was associated with a significantly lower risk for CIN 2+ (PPV=21%) as compared with LSIL-H (PPV=40%). The results showed that the risk of CIN 2+ was intermediate for LSIL-H compared with unqualified LSIL (p<0.005) and HSIL (p<0.0001). ConclusionsThe current study is one of the largest LSIL-H series to date. Because of its intermediate status between LSIL and HSIL, LSIL-H should be considered a distinct diagnostic category, and specific cytomorphological criteria should be defined. The results suggest that an LSIL-H diagnostic category would aid in more rapid detection and treatment in some patients with CIN 2+.

Randomized healthservices study of human papillomavirus‐based management of low‐grade cytological abnormalities

Human papillomavirus (HPV)-based management of women with borderline atypical squamous cells of undetermined significance (ASCUS) or mildly abnormal cervical intraepithelial neoplasia (CINI) cervical cytology has been extensively studied in the research setting. We wished to assess safety and health care resource use of a real-life health care policy using HPV triaging. All 15 outpatient clinics involved in the organized population-based screening program in Stockholm, Sweden screening program were randomized to either continue with prior policy (colposcopy of all women with ASCUS/CINI) or to implement a policy with HPV triaging and colposcopy only of HPV-positive women. The trial enrolled the 3,319 women who were diagnosed with ASCUS (n = 1,335) or CINI (n = 1,984) in Stockholm during 17th March 2003 to 16th January 2006. Detection of high-grade cervical lesions (CINII+) and health care cost consumption was studied by registry linkages. The proportion of histopathology-verified CINII+ was similar for the two policies (395 of 1,752 women (22.5%; 95% Confidence interval [CI]: 20.6-24.6%) had CINII+ diagnosed with HPV triaging policy, 318 of 1,567 women (20.3%; 95%CI: 18.3-22.4%) had CINII+ with colposcopy policy). Sixty-four percent of women with ASCUS and 77% of women with CINI were HPV positive. HPV-positivity was age-dependent, with 81% of women below 35 years of age and 44% of women above 45 years of age testing HPV-positive. HPV triaging was cost-effective only above 35 years of age. In conclusion, a real-life randomized healthservices study of HPV triaging of women with ASCUS/CINI demonstrated similar detection of CINII+ as colposcopy of all women.

Accuracy of the Papanicolaou test in the detection of high-grade cervical lesions

most commonly used method (62.7%) in the present study—with IUDs reported as the current/most recent form of contraception by only 16.7%. Thesefindings are supported by a recent study inwhich condoms were the most commonly used contraceptive method for women attending a family-planning clinic in Shanghai [3]. In total, 21.1% of women reported currently usingmore than 1method of contraception, 8.8% of whom reported using condoms in addition to another form. However, “current use”may not be the same as “simultaneous use,” so these findings should be interpreted with caution. Of note, the median number of abortions was 2, indicating the need for further research into the use of induced abortion as a familyplanningmethod in China. Traditionalmethods such aswithdrawal and rhythm were the second and third most commonly reported methods, respectively, which may indicate the need for more comprehensive family-planning education. The media was cited as the most common information source regarding contraception—ahead of doctors, nurses, and family-planning clinics; thus, evaluation of media messages may be warranted. Despite the biases associated with recruiting women from a gynecology outpatient clinic at a large tertiary-care hospital—where women are likely to havemore access to contraception than arewomen in other settings—the present study provided valuable information about the chosen methods of contraception in urban China.

Can HPV testing replace the pap smear?

The most compelling question in evaluating the possible replacement of the conventional Papanicolaou smear from a high-risk HPV testing method is the balance between specificity and sensitivity for detection of cervical intraepithelial neoplasia grade ≥CIN 2 (CIN 2+). Multiple studies have shown that HPV testing has higher sensitivity than cytology for the detection of high-grade CIN. Positivity increases the test cut-off for HPV and may reduce false positive results without significantly compromising the sensitivity, potentially alleviating the concern of low specificity. Overall, available evidence convincingly shows that HPV testing is superior to traditional screening for the detection of high-grade cervical lesions, and efforts are focused on improving its sensitivity, either by increasing its cut-off for positivity or by selecting those subgroups where HPV testing is expected to have higher positive predictive value for cervical disease, or by seeking to optimize triage tests after a positive HPV result.

Cytology versus HPV testing for the detection of high-grade cervical lesions in women found positive on visual inspection in Mumbai, India

Objective To compare the utility of cytology and HPV testing in women from Mumbai, India, suspected of having cervical intraepithelial neoplasia (CIN) on visual inspection with acetic acid (VIA), Lugol's iodine (VILI), or both. Method The sensitivity, specificity, and predictive values of these tests for the detection of CIN 2 and/or 3 were evaluated in this cross-sectional study with 756 women suspected of having CIN on visual inspection. Results There were 25 women with CIN 2, 20 with CIN 3, and 21 with invasive cancer. The sensitivity to detect CIN 3 lesions was 85.0% (95% CI, 62.1–96.8) and 70.0% (95% CI, 45.7–88.1) for cytology testing at the ASCUS and LSIL thresholds, respectively, and it was 89.5% (95% CI, 66.9–98.7) for HPV testing. The specificity to detect CIN 3 lesions was 94.5% (95% CI, 92.5–96.1) and 96.1% (95% CI, 94.4–97.5) for cytology testing at the ASCUS and LSIL thresholds, and it was 91.1% (95% CI, 88.5–93.2) for HPV testing. Conclusion Cytology and HPV testing were both found to be accurate triaging methods for women suspected of having CIN on visual inspection, especially for those with CIN 3 lesions.

O796 Accuracy of the Papanicolaou test in the detection of high-grade cervical lesions

International Journal of Gynecology & ObstetricsVolume 107, Issue S2 p. S321-S321 Free communication (oral) presentations O796 Accuracy of the Papanicolaou test in the detection of high-grade cervical lesions A. Repše Fokter, A. Repše FokterSearch for more papers by this authorA. Strahovnik, A. StrahovnikSearch for more papers by this author A. Repše Fokter, A. Repše FokterSearch for more papers by this authorA. Strahovnik, A. StrahovnikSearch for more papers by this author First published: 06 October 2011 https://doi.org/10.1016/S0020-7292(09)61169-3AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume107, IssueS2Abstracts of XIX FIGO World Congress of Gynecology and ObstetricsOctober 2009Pages S321-S321 RelatedInformation

Comparison of the Hybrid Capture II Assay With the Human Papillomavirus DNA Chip Test for the Detection of High-Grade Cervical Lesions

Cervical intraepithelial neoplasia (CIN) 2 is used as the threshold for treatment decisions. This study was conducted to evaluate the clinical efficacy of the Hybrid Capture II assay (HC2) and the human papillomavirus (HPV) DNA chip test (HDC) for detecting HPV in high-grade cervical lesions CIN2 or greater, including adenocarcinoma (CIN2+). Seven hundred forty-one women with abnormal cervical cytology were evaluated with the HC2, the HDC, and histological assessment of the cervix. The overall agreement of the 2 HPV tests was 88.8% (kappa value, 0.61). Of 615 high-risk HPV-positive specimens by the HC2, 571 (92.8%) were HDC-positive. Both tests were performed similarly on CIN2+ samples; the sensitivities of the HC2 and HDC as predictors of CIN2+ were 93.4 and 92.6%, respectively. In 83 cases of discrepancies between the HC2 and HDC, genotyping of 39 HC2-negative/HDC-positive cases revealed 13 HPV-53, 8 HPV-58, 7 HPV-16, 6 HPV-18, 2 HPV-68, 1 HPV-31, 1 HPV-45, and 1 HPV-66. In 515 patients with CIN2+, HPV-16 (45.0%) was the most common type; the next most common types were HPV-58 (20.8%), HPV-18 (16.1%), HPV-31 (6.6%), and HPV-33 (6.6%). Human papillomavirus types 16, 58, and 18 were more likely associated with CIN2+ (P < 0.05). In conclusion, the HDC is a reliable diagnostic tool for the detection of CIN2+. In addition, the HDC provides useful information regarding viral genotypes.

Comparison of Human Papillomavirus Detection and Typing by Hybrid Capture 2, Linear Array, DNA Chip, and Cycle Sequencing in Cervical Swab Samples

Although the Hybrid Capture II (HC II) assay can detect 13 high-risk human papillomavirus (HPVs), it does not yield any genotype-specific information. We evaluated the performance of 4 HPV DNA tests, namely, HC II, Linear Array (LA), DNA chip, and cycle sequencing for their capacity to detect the presence of high-risk HPV DNA and HPV-associated cervical lesions. Seventy-six women who were referred to the colposcopy clinic for abnormal cytology were enrolled. The women were examined using liquid-based cytology, colposcopy-directed biopsy, and HPV DNA tests. After DNA extraction from a single sample, HPV DNA tests were performed by all 4 methods on the same specimen. The LA test has higher HPV-positive rates than HC II for cervical intraepithelial neoplasia I (83.3% vs 61.1%; P < 0.01) and for cervical intraepithelial neoplasia II and more severe lesions (100.0% vs 80.0%; P < 0.01). The concordance between the DNA chip and LA tests was 89.5%, confirming substantial agreement (kappa coefficient = 0.73), and the concordance between HC II and the DNA chip was 80.3%, also showing substantial agreement (kappa coefficient = 0.738). The concordance for 15 high-risk HPV genotypes between LA and sequencing was 82.5% with a kappa value of 0.536. Furthermore, the LA test was more sensitive in the detection of high-grade cervical lesions than HC II (100% vs 92.3%, P < 0.01). The LA test showed superior sensitivity in the detection of clinically relevant HPV infections and has proven to be an accurate tool for identifying individual HPV types, especially in cases of multiple HPV infections.