Detection Of Squamous Intraepithelial Lesions Research Articles

Does Absence of Transformation Zone Component in Anal Cytology Sample Affects Detection of Squamous Intraepithelial Lesions?

Does Absence of Transformation Zone Component in Anal Cytology Sample Affects Detection of Squamous Intraepithelial Lesions?

High-risk human papillomavirus genotyping in women with atypical squamous cells of undetermined significance

We conducted a prospective study to evaluate the prevalence of high-risk human papillomavirus (hr-HPV) positivity in women with atypical squamous cells of undetermined significance (ASC-US). Additionally, we assessed the association of hr-HPV positivity with the pathology of high-grade squamous intraepithelial lesions or worse (HSIL+) and the risk of subsequent detection of squamous intraepithelial lesions. A total of 376 women were included, with 242 (64.4%) exhibiting hr-HPV positivity. The predominant HPV genotypes were 16, 52 and 58. Factors associated with the immediate detection of HSIL+ pathology included a colposcopic impression of high-grade lesions, hr-HPV positivity, HPV 16 positivity, HPV 18 positivity, HPV 58 positivity, age less than 40 years, and biopsy of two or more pieces. However, only the first three factors were statistically significant in multivariate analysis. Among the 291 women who continued surveillance for 6 months or more, the median follow-up period was 41.8 months (interquartile range [IQR] 26.5–54.0). The prevalence of subsequent HSIL in women with hr-HPV positivity versus negativity was 3.6% versus 0.98%, respectively. The median time to the subsequent detection of SIL was 28.7 months (IQR 14.9–41.7). In conclusion, women with ASC-US in our study had a high proportion of hr-HPV positivity. Type-specific HPV testing could play a pivotal role in the development of specific management protocols for women with ASC-US.Clinical trial registration: https://thaiclinicaltrials.org, TCTR20161017002.

HPV Cotesting of Unsatisfactory Papanicolaou Tests: Implications for Follow-up Intervals.

The 2019 American Society of Colposcopy and Cervical Pathology management guidelines recommend that patients with an unsatisfactory Papanicolaou (Pap) test (UPT) and negative human papillomavirus (HPV) cotest undergo repeat age-based screening in 2 to 4 months. The rationale is that a negative HPV test in the setting of an UPT may reflect an inadequate sample and therefore should not be interpreted as truly "negative." For patients 25 years and older who are cotested, if HPV is positive for the 16 or 18 genotypes, direct referral for colposcopy is recommended. Our study aimed to determine if a negative HPV cotest result is predictive of the absence of a high-grade squamous intraepithelial lesion (HSIL) and whether these patients may be called back for repeat testing at an interval longer than 2 to 4 months. Follow-up cervical cytology and biopsy results in women with UPT and HPV cotests from January 2017 to December 2021 were collected. Original UPT and HPV cotest results were correlated with the follow-up Pap and biopsy results. There were 1,496 (2.28%) UPT cases out of 65,641 total Pap tests. Among the 1,496 UPT cases, 1,010 (67.5%) had HPV cotesting; 676 (45.1%) were followed by repeat Pap or biopsy within 4 months and 850 (56.8%) within 12 months. The total follow-up rate was 81%, with a range of 3 days to 36 months. The HSIL rate in HPV-positive cases was 5.7% (3/53) vs 0.4% (2/539) (P = .006) in HPV-negative cases. In UPT, HPV cotesting showed negative predictive values for low-grade and high-grade squamous intraepithelial lesion detection of 98.5% and 99.6%, respectively, while positive predictive values were 19% and 5.7%. A negative HPV cotest in individuals with UPT predicted the lack of HSIL in our study. Compliance with the recommended follow-up time of 2 to 4 months for women with UPT was low (45.1%). Our study suggests that women with UPT and negative HPV cotest may be safely called back at an interval longer than 4 months.

Assessing colposcopic accuracy for high\u2010grade squamous intraepithelial lesion detection: a retrospective, cohort study

BackgroundInappropriate management of high-grade squamous intraepithelial lesions (HSIL) may be the result of an inaccurate colposcopic diagnosis. The aim of this study was to assess colposcopic performance in identifying HSIL+ cases and to analyze the associated clinical factors.MethodsRecords from 1130 patients admitted to Shenzhen Maternal and Child Healthcare Hospital from 12th January, 2018 up until 30th December, 2018 were retrospectively collected, and included demographics, cytological results, HPV status, transformation zone type, number of cervical biopsy sites, colposcopists’ competencies, colposcopic impressions, as well as histopathological results. Colposcopy was carried out using 2011 colposcopic terminology from the International Federation of Cervical Pathology and Colposcopy. Logistic regression modelling was implemented for uni- and multivariate analyses. A forward stepwise approach was adopted in order to identify variables associated with colposcopic accuracy. Histopathologic results were taken as the comparative gold standard.ResultsData from 1130 patient records were collated and analyzed. Colposcopy was 69.7% accurate in identifying HSIL+ cases. Positive predictive value, negative predictive value, sensitivity and specificity of detecting HSIL or more (HSIL+) were 35.53%, 64.47%, 42.35% and 77.60%, respectively. Multivariate analysis highlighted the number of biopsies, cytology, and transformation zone type as independent factors. Age and HPV subtype did not appear to statistically correlate with high-grade lesion/carcinoma.ConclusionEvidence presented here suggests that colposcopy is only 69.7% accurate at diagnosing HSIL. Even though not all HSIL will progress into cancer it is considered pre-cancerous and therefore early identification will save lives. The number of biopsies, cytology and transformation zone type appear to be predictors of misdiagnosis and therefore should be considered during clinical consultations and by way of further research.

High-Resolution Anoscopy Surveillance After Anal Squamous Cell Carcinoma: High-Grade Squamous Intraepithelial Lesion Detection and Treatment May Influence Local Recurrence.

BACKGROUND:Local recurrence is a significant risk after anal squamous cell carcinoma.OBJECTIVES:This study aimed to examine the occurrence of high-grade squamous intraepithelial lesions and local recurrence after anal cancer at surveillance with high-resolution anoscopy.DESIGN:This is a retrospective observational study.SETTING:This study was conducted at an anogenital neoplasia referral center.PATIENTS:There were 76 anal/perianal cancers from 1998 to 2018. Sixty-three patients were eligible and 3 were excluded, for a total of 60 patients; 35 of 60 (58%) patients were male.INTERVENTION:High-resolution anoscopy after chemoradiation or excision only for anal squamous cell carcinoma was performed.MAIN OUTCOME MEASURES:The primary outcomes measured were local recurrence and high-grade squamous intraepithelial lesion detection rates.RESULTS:Sixty patients, 27% HIV positive, underwent surveillance over a median 42 (range 7–240) months of follow-up. Seven had had a prior local recurrence at study entry so were analyzed separately. Thirty of 53 underwent chemoradiation (57%) and 23 of 53 underwent excision alone (43%); 33 had perianal cancer and 20 had anal cancer. Ten of 30 of the chemoradiation group had had stage 1 (33%) disease in comparison with 22 of 23 of the excision only group (96%, p < 0.001).OUTCOMES:High-grade squamous intraepithelial lesions were detected in 4 of 30 (13%) patients after chemoradiation and in 17 of 23 (74%) patients after excision only (p < 0.001). Twenty of 21 (95%) high-grade lesions were treated with ablation. Six of 7 (86%) patients with prior local recurrence had high-grade squamous intraepithelial lesions over a median of 21 months follow-up. One local recurrence (T1N0M0) occurred during surveillance after primary chemoradiation (0.56/1000 person-months), none occurred after excision only, and 2 of 7 with prior local recurrence developed further local recurrence (6.86/1000 person-months). All 3 local recurrences occurred after treatment of high-grade squamous intraepithelial lesions. There were no metastases, abdominoperineal excisions, or deaths from anal squamous cell carcinoma.LIMITATIONS:Retrospective data were used for this study.CONCLUSIONS:High-grade squamous intraepithelial lesions after anal squamous cell carcinoma are more common after excision only than after chemoradiation. Local recurrence is low in this high-resolution anoscopy surveillance group in which high-grade squamous intraepithelial disease was ablated. Excision of small perianal cancers appears safe; however, a subset of patients is at excess risk. See Video at http://links.lww.com/DCR/B285.VIGILANCIA POR ANOSCOPÍA DE ALTA RESOLUCIÓN EN CASOS DE CARCINOMA ANAL A CÉLULAS ESCAMOSAS: LA DETECCIÓN Y TRATAMIENTO DE UNA LESIÓN INTRAEPITELIAL ESCAMOSA DE ALTO GRADO (HSIL) PUEDE INFLUIR EN LA RECURRENCIA LOCALANTECEDENTES:La recurrencia local tiene un riesgo significativo después del carcinoma anal a células escamosas.OBJETIVO:Evaluar la aparición de lesiones intraepiteliales escamosas de alto grado (HSIL) y su recurrencia local durante la vigilancia con anoscopía de alta resolución en casos de cancer anal.DISEÑO:Estudio observacional retrospectivo.AJUSTE:Centro de referencia de neoplasia anogenital.PACIENTES:Se diagnosticaron 76 cánceres anales / perianales entre 1998 y 2018. Un total de 63 pacientes fueron elegidos, 3 excluidos (n = 60), 35/60 (58%) fueron varones.INTERVENCIÓN:Anoscopía de alta resolución después de la quimio-radioterapia, o solo excisión en casos de carcinoma anal a células escamosas.PRINCIPALES MEDIDAS DE RESULTADO:Recurrencia local primaria y tasas de detección de lesión intraepitelial escamosa de alto grado.RESULTADOS:Sesenta pacientes, 27% VIH positivos, fueron sometidos a vigilancia durante una mediana de 42 (rango 7–240) meses de seguimiento. Siete habían tenido una recurrencia local antes de ser incluidos en el estudio, por lo que se analizaron por separado. Treinta de 53 se sometieron a quimio-radioterapia (57%) y 23/53 solo a excisión (43%). 33 eran lesiones perianales, 20 de canal anal. 10/30 del grupo de quimio-radioterpia se encontraban en Fase 1 (33%) comparados con 22/23 del grupo de excisión (96%, p <0.001).RESULTADOS:Se detectaron lesiones intraepiteliales escamosas de alto grado en 4/30 (13%) después de la quimio-radioterapia, y en 17/23 (74%) solo después de la excisión (p < 0.001). 20/21 (95%) lesiones de alto grado fueron tratadas con ablación. Seis de siete (86%) con recurrencia local previa tenían lesiones intraepiteliales escamosas de alto grado durante una mediana de seguimiento de 21 meses. Se produjo una recurrencia local (T1N0M0) durante la vigilancia después de la quimio-radioterapia primaria (0.56/1000 persona-meses), ninguna después de la excisión sola y 2/7 con recurrencia local previa desarrollaron una recurrencia local adicional (6.86/1000 persona-meses). Las 3 recidivas locales ocurrieron después del tratamiento de las lesiones intraepiteliales escamosas de alto grado. No hubieron metástasis, excisiones abdominoperineales o muertes por carcinoma anal a células escamosas.LIMITACIONES:Datos retrospectivos.CONCLUSIONES:Las lesiones intraepiteliales escamosas de alto grado en casos de carcinoma escamocelular anal son más comunes después de la excisión sola que después de la quimio-radioterapia. La recurrencia local es baja en este grupo de vigilancia de anoscopía de alta resolución en el que se retiró la enfermedad intraepitelial escamosa de alto grado. La excisión de pequeños cánceres perianales parece segura; sin embargo, un subconjunto de pacientes tiene un riesgo excesivo. Consulte Video Resumen en http://links.lww.com/DCR/B285. (Traducción—Dr. Xavier Delgadillo)

Implementation of and Early Outcomes From Anal Cancer Screening at a Community-Engaged Health Care Facility Providing Care to Nigerian Men Who Have Sex With Men.

PURPOSEAnal cancer risk is substantially higher among HIV-infected men who have sex with men (MSM) as compared with other reproductive-age adults, but screening is rare across sub-Saharan Africa. We report the use of high-resolution anoscopy (HRA) as a first-line screening tool and the resulting early outcomes among MSM in Abuja, Nigeria.METHODSFrom August 2016 to August 2017, 424 MSM enrolled in an anal cancer screening substudy of TRUST/RV368, a combined HIV prevention and treatment cohort. HRA-directed biopsies were diagnosed by histology, and ablative treatment was offered for high-grade squamous intraepithelial lesions (HSIL). HRA proficiency was assessed by evaluating the detection of squamous intraepithelial lesions (SIL) over time and the proportion biopsied. Prevalence estimates of low-grade squamous intraepithelial lesions and HSIL with 95% CIs were calculated. Multinomial logistic regression was used to identify those at the highest risk of SIL.RESULTSMedian age was 25 years (interquartile range [IQR], 22-29), median time since sexual debut was 8 years (IQR, 4-12), and 59% (95% CI, 54.2% to 63.6%) were HIV infected. Rate of detection of any SIL stabilized after 200 screenings, and less than 20% had two or more biopsies. Preliminary prevalence estimates of low-grade squamous intraepithelial lesions and HSIL were 50.0% (95% CI, 44.7% to 55.3%) and 6.3% (95% CI, 4.0% to 9.3%). HIV infection, at least 8 years since anal coital debut, concurrency, and external warts were independently statistically associated with SIL.CONCLUSIONProficiency with HRA increased with experience over time. However, HSIL detection rates were low, potentially affected by obstructed views from internal warts and low biopsy rates, highlighting the need for ongoing evaluation and mentoring to validate this finding. HRA is a feasible first-line screening tool at an MSM-friendly health care facility. Years since anal coital debut and external warts could prioritize screening.

Comparative study of squamous intraepithelial lesion detection and unsatisfactory rates between liquid-based cytology and conventional smears from a split sample in cervical cancer screening: A Japanese experience

Comparative study of squamous intraepithelial lesion detection and unsatisfactory rates between liquid-based cytology and conventional smears from a split sample in cervical cancer screening: A Japanese experience

Detection Rate of High-Grade Squamous Intraepithelial Lesions as a Quality Assurance Metric for High-Resolution Anoscopy in HIV-Positive Men.

High-resolution anoscopy-guided biopsies are the gold standard for identifying anal intraepithelial neoplasia, but diagnosing high-grade squamous intraepithelial lesions depends on the skills of the anoscopist. This study aims to validate the high-grade squamous intraepithelial lesion detection rate as a quality assurance metric for high-resolution anoscopy in HIV-positive men. This is a retrospective study. This study was conducted at 3 HIV outpatient clinics in Amsterdam, The Netherlands. HIV-positive men who have sex with men were selected for this study. We analyzed the high-grade squamous intraepithelial lesion detection rate per high-resolution anoscopy, the mean number of biopsies taken, and the mean high-grade squamous intraepithelial lesion rate per biopsy in time-subsequent groups for 7 anoscopists performing high-resolution anoscopy. Seven anoscopists performed high-resolution anoscopy in 1340 HIV-positive men who have sex with men. The overall high-grade squamous intraepithelial lesion detection rate for all 7 anoscopists combined increased significantly over time, from 27% to 40% (p < 0.001; OR, 1.15; 95% CI, 1.08-1.23 per 50 high-resolution anoscopies). The mean number of biopsies increased significantly from 1.4 (22% high-grade squamous intraepithelial lesions per biopsy) to 2.0 biopsies per patient (29% high-grade squamous intraepithelial lesions per biopsy) (p < 0.001). Three anoscopists showed a significant increase in proportion of high-grade squamous intraepithelial lesions per biopsy with increasing experience. There were statistically significant differences, with limited clinical significance, in the characteristics of patient populations between anoscopists and clinics. We found significant variations in the high-grade squamous intraepithelial lesion detection rate among anoscopists performing high-resolution anoscopy in HIV-positive men who have sex with men. The high-grade squamous intraepithelial lesion detection rate and mean high-grade squamous intraepithelial lesion rate per biopsy can be used as a quality assurance metric to follow up the learning curve of high-resolution anoscopists. See Video Abstract at http://links.lww.com/DCR/A555.

Efficacy of p16 and Ki-67 immunostaining in the detection of squamous intraepithelial lesions in a high-risk HPV group.

p16 and Ki-67 immunohistochemistry can be used as an ancillary method for the diagnosis of squamous intraepithelial lesion (SIL) versus atrophic change and atypical squamous metaplasia. The aim of the present study was to evaluate the efficacy of these two immunohistochemical markers in the accurate interpretation of cervical biopsies and correlate this data with human papilloma virus (HPV) infection status. The study included 103 formalin-fixed cervical punch and cone biopsy samples, with corresponding HPV DNA test data. Histopathological staining with hematoxylin and eosin, and immunohistochemical staining for p16 and Ki-67 were reviewed by two pathologists. The positivity of p16 and Ki-67 increased significantly with the severity of the cervical lesion in patients with a high-risk-HPV (HR-HPV) infection status (P<0.001). However, there was discordance in the HPV-negative group. Furthermore, concomitant diffuse, strong and block positive staining of p16, and a high Ki-67 index were implicated in high-grade SIL in the HR-HPV group. Thus, the two markers were efficient in advancing the diagnostic accuracy of cervical biopsies in the HR-HPV group; however, application of immunohistochemical results should be carefully considered in the HPV-negative group.

Performance of the HPV-16 L1 methylation assay and HPV E6/E7 mRNA test for the detection of squamous intraepithelial lesions in cervical cytological samples

HPV-16 L1 methylation and E6/E7 mRNA have suggested that they had close relationship with cervical neoplastic progression. This study aimed to evaluate the clinical performance of the HPV-16 L1 methylation assay and E6/E7 mRNA test for detecting high-grade cervical lesions (CIN2+). A total of 81 women with liquid-based cytology (LBC) samples, histological results, and positive HPV–DNA test for HPV type 16 only were included in this study. HPV-16 L1 methylation and E6/E7 mRNA levels were measured using methylation-sensitive high resolution melting (MS-HRM) analysis and Quantivirus®HPV E6/E7 RNA 3.0 assay (bDNA), respectively, in the same residue of LBC samples. The current date showed a positive correlation between the HPV-16 L1 methylation and the E6/E7 mRNA levels. The L1 methylation and mRNA levels both increased with disease severity. The mRNA test method showed higher sensitivity and NPV (98.0 and 91.7% vs. 89.8 and 80.8%), while lower specificity and PPV (34.4 and 69.6% vs. 65.6 and 80.0%), than the L1 methylation assay for detecting histology-confirmed CIN2+. When using the detection method of mRNA test combined with L1 methylation assay, we obtained a sensitivity of 89.8% and a specificity of 71.9%.These findings suggest that assessment of HPV-16 L1 methylation testing combined with E6/E7 mRNA testing may be a promising method for the triage of women with HPV type 16 only.

Use of colposcopy for detection of squamous intraepithelial lesions

Introduction Pap smear, the main tool of cervical cancer screening is not always available, but some patients are in urgent need for proper diagnostic. Aim of this article was to investigate accuracy of colposcopy for detection of squamous intraepithelial lesions of low or high grade (LGSIL, HGSIL) and to promote colposcopy as useful tool for detection of patients in need for immediate further diagnostics. Methods Prospective multicentric study performed in B&amp;H in 2012 -2013 included 87 patients with colposcopic images related to squamous intraepithelial lesion (SIL) who formed experimental group: 56 patients with colposcopic images related to LGSIL and 31 patients related to HGSIL. Control group included 50 patients without colposcopic abnormalities. To test accuracy of colposcopy, PAP smear and histology were used. For statistical analysis χ2 was used.Results 94.5% patients in experimental group had abnormal PAP test: 64.3% correlated to LGSIL (χ2= 60.48 P &lt; 0.0001), while 64.5% correlated to HGSIL (χ2 = 54.23 P&lt;0.0001) Odds Ratio = 490; 95% CI = 42.024 to 5713.304). HGSIL was confirmed in 27 (87%) cases by histology (CIN II /CIN III). There were no statistically significant differences between colposcopic finding and histology results (Yates-corrected χ2 = 0.33 P = .5637)Conclusions This study showed high level of correlation between colposcopy and PAP results (63-64%) and to histology for HGSIL (87%). In absence of PAP test colposcopy could be used to select patients in need for biopsy.

Evaluation of a Low-Cost Liquid-Based Pap Test in Rural El Salvador

We sought to test the diagnostic efficacy of a low-cost, liquid-based cervical cytology that could be implemented in low-resource settings. A prospective, split-sample Pap study was performed in 595 women attending a cervical cancer screening clinic in rural El Salvador. Collected cervical samples were used to make a conventional Pap (cell sample directly to glass slide), whereas residual material was used to make the liquid-based sample using the ClearPrep method. Selected samples were tested from the residual sample of the liquid-based collection for the presence of high-risk Human papillomaviruses. Of 595 patients, 570 were interpreted with the same diagnosis between the 2 methods (95.8% agreement). There were comparable numbers of unsatisfactory cases; however, ClearPrep significantly increased detection of low-grade squamous intraepithelial lesions and decreased the diagnoses of atypical squamous cells of undetermined significance. ClearPrep identified an equivalent number of high-grade squamous intraepithelial lesion cases as the conventional Pap. High-risk human papillomavirus was identified in all cases of high-grade squamous intraepithelial lesion, adenocarcinoma in situ, and cancer as well as in 78% of low-grade squamous intraepithelial lesions out of the residual fluid of the ClearPrep vials. The low-cost ClearPrep Pap test demonstrated equivalent detection of squamous intraepithelial lesions when compared with the conventional Pap smear and demonstrated the potential for ancillary molecular testing. The test seems a viable option for implementation in low-resource settings.

The Significance of Augmented High-Grade Squamous Intraepithelial Lesion Detection on Pap Test Examination: Partial Results from the RODEO Study Team

Objective: This study sought to ascertain the significance of augmented high-grade squamous intraepithelial lesion (HSIL) detection by Pap test using both conventional smear and liquid-based cytology (LBC) in a high-risk population. Study Design: We conducted a direct-to-vial study to compare the diagnostic performance of Pap smear versus LBC in a high-risk population of women referred for colposcopy at a gynecologic ambulatory clinic at the Barretos Cancer Hospital in Brazil during 2011. Results: The detection of both low-grade squamous intraepithelial lesions (LSILs) and HSILs was significantly greater (p = 0.04 and p = 0.033, respectively) in the LBC arm [84 LSIL cases (5.7%) and 148 HSIL cases (10.1%)] than in the conventional smear arm [66 LSIL cases (4.1%) and 126 HSIL cases (7.9%)]; however, no differences were found for invasive squamous carcinoma or adenocarcinoma (p = 0.678). Of 3,071 women who were examined cytologically (1,604 conventional preparations and 1,467 LBC) and colposcopically, biopsies were available for 279 conventional preparations (17.6%) and 325 LBC preparations (22.2%). No significant differences were found between the methods with respect to diagnostic performance. Conclusion: LBC was significantly superior to conventional smears for the detection of LSILs and HSILs, but these results did not influence biopsy confirmation. Both methods showed similar performances with high positive predictive values but very low sensitivities.

Performance of computer-assisted imaging system in detection of squamous intraepithelial lesion of uterine cervix

To evaluate the performance of computer-assisted imaging system in the detection of cervical squamous intraepithelial lesion and quality-assurance. Manual PAP screening (n = 140 580) and image-assisted screening (n = 32 885) were compared for the detection rates of squamous cell abnormalities, the atypical squamous cells (ASC) to squamous intraepithelial lesion (SIL) ratio, the positive rates of high risk human papillomavirus (HR-HPV) test in the case of atypical squamous cells of undetermined significance (ASC-US), and the correlation between cytopathology and histopathology. Compared with manual screening, computer-assisted imaging system showed increased overall positive detection by 0.32%, decreased detection of ASC by 0.21%, increased detection of low-grade squamous intraepithelial lesion (LSIL) by 0.22%, increased detection of high-grade squamous intraepithelial lesion or worse (HSIL) by 0.31%, and decreased ASC to SIL ratio from 2.59 to 1.60. Computer-assisted imaging system did not change the HR-HPV positive rate of the patients who were ASC-US, or the coincidence rate between cytopathology and histopathology. Moreover, the productivity of the laboratory operation increased 58.33%. Computer-assisted imaging system significantly increases the overall positive detection rate of cervical SIL, improves accuracy and work efficiency of screening, decreases the ASC/SIL rate, and strengths the quality-assurance of laboratory testing.

No Association between Endogenous Retinoic Acid and Human Papillomavirus Clearance or Incident Cervical Lesions in Brazilian Women

Although oncogenic human papillomavirus (HPV) infections have been established as the necessary cause of cervical cancer, most HPV infections are transient and rarely progress to squamous cervical lesions. The activity of HPV is tightly associated with epithelial cell differentiation; therefore, regulators of differentiation, such as retinoic acid (RA), have been considered targets for the prevention of HPV-associated squamous intraepithelial lesion (SIL) development. The purpose of this study was to determine the association between circulating RA and early events in cervical carcinogenesis, specifically type-specific HPV clearance and SIL detection. Archived blood samples from 643 women participating in the Ludwig-McGill Cohort in São Paulo, Brazil, were analyzed by high-pressure liquid chromatography for three RA isomers (all-trans, 13-cis, and 9-cis-RA). A type-specific HPV clearance event was defined as two consecutive visits negative for an HPV type during follow-up for 364 HPV-positive women. Among the 643 women in this analysis, 78 were diagnosed with incident SIL. The probability of clearing an oncogenic HPV infection was not significantly different across RA isomer quartiles. There was a suggestion that increasing all-trans-RA increased the rate of nononcogenic HPV clearance (P-trend = 0.05). There was no association observed between serum RA levels and incident SIL. Our results suggest that elevated circulating RA isomer levels do not increase the rate of HPV clearance or reduce the risk of incident SIL. The role of RA in the inhibition of HPV-induced carcinogenesis, as shown in vitro, lacks confirmatory evidence within epidemiologic studies among women.

The use of p16INK4A immunocytochemistry in “Atypical squamous cells which cannot exclude HSIL” compared with “Atypical squamous cells of undetermined significance” in liquid‐based cervical smears

Even though p16(INK4a) (p16) immunocytochemistry has proven a useful accessory tool verifying the identification of atypical squamous cells of undetermined significance (ASC-US) categorized smears, the procedure still has limitations. To date few studies examining the usefulness of p16 immunocytochemistry in atypical squamous cells which cannot exclude HSIL (ASC-H), compared with ASC-US in liquid-based cervical smears. Therefore, we examined the correlation of p16 immunocytochemical staining with follow-up biopsy results on ASC-H categorized smears and compared the data with those classified as ASC-US on 105 liquid-based cytology samples. We found no statistical significance in the p16 expression of ASC-US smears and the presence of squamous intraepithelial lesions (SIL) in follow-up biopsies (p = 0.546). However, p16 expression did significantly correlate with the presence of SIL (p = 0.002) in ASC-H smears. There was a statistically significant relationship between p16 expression and presence of high grade squamous intraepithelial lesions (HSIL) or more on the follow-up biopsies in both ASC-US (p = 0.012) and ASC-H (p < 0.001) categorized smears. In ASC-US categorized smears, there was no statistical significance between p16 expression and the HR-HPV viral load (p = 0.091). But there was a statistical significance between p16 expression and the HR-HPV viral load (p < 0.001) in ASC-H categorized smears. Our results indicate that p16 immunostaining is a much better useful marker for HR-HPV infection and detection of SIL in ASC-H categorized smears compared to those defined as ASC-US.

The significance of endocervical cells and metaplastic squamous cells in liquid‐based cervical cytology

We conducted a retrospective study to investigate whether the presence or absence of endocervical cells (EC) and metaplastic squamous cells (MSC) was associated with the detection of squamous intraepithelial lesions in liquid-based cervical cytology. 90,376 cases of liquid-based cervical cytology smears received in 2006 were included in the study. Low-grade (LSIL) and high-grade squamous intraepithelial lesions (HSIL) were classified according to the Bethesda system (2001). The rates of detecting LSIL and HSIL in smears with and without EC and/or MSC were determined. There were 1,540 LSIL and 396 HSIL. The ratio of HSIL/NILM (no intraepithelial lesion or malignancy) was 0.0022 in smears without EC or MSC, 0.0040 in smears with EC only, 0.0044 in smears with MSC only, and 0.0056 in smears with both EC and MSC present. Compared with smears without EC or MSC, this ratio was significantly higher (P < 0.05) when either EC or MSC was present. Compared with smears with EC only, the ratio was also significantly higher when both EC and MSC were present (P < 0.05). On the other hand, the presence or absence of EC had no effect on the detection rate of LSIL (0.0191 for both groups), while the presence of MSC was actually associated with lower detection rate of LSIL (0.0153, P < 0.05). The presence of endocervical and metaplastic cells was associated with higher detection rates of HSIL. MSC was associated with lower detection or LSIL.

Association of cutaneous anergy with human papillomavirus and cervical neoplasia in HIV-seropositive and seronegative women

Cutaneous anergy testing evaluates delayed type hypersensitivity responses and is, in essence, an in-vivo measure of cell-mediated immune function at an epithelial surface. This study assessed the relationship of anergy test results with cervical infection by human papillomavirus (HPV) and cervical neoplasia in HIV-seropositive and seronegative women. HIV-seropositive (n = 1029) and HIV-seronegative (n = 272) women enrolled in a long-term cohort study were followed semi-annually with HPV-DNA testing and cytology. Anergy was defined as unresponsiveness to Candida albicans, tetanus toxoid, and mumps antigen. Anergy was associated with the prevalent detection of squamous intraepithelial lesions [SIL; adjusted odds ratio 1.70; 95% confidence interval (CI) 1.16-2.48] in multivariable logistic regression models, and with the incident detection of oncogenic HPV (adjusted hazard ratio 1.24; 95% CI 0.99-1.56) in multivariable Cox regression models. These models adjusted for HIV infection, combined CD4 T-cell and HIV-RNA strata (13 separate strata to control optimally for their interactive effects), as well as other variables. Cutaneous anergy testing may measure aspects of local cellular immune function in epithelial tissues that are important for the control of HPV and development of SIL, and that in HIV-seropositive women are not fully accounted for by circulating CD4 T-cell counts and HIV-RNA levels.

Direct‐to‐vial comparison of a new liquid‐based cytology system, liqui‐PREP™ versus the conventional Pap smear

The objective of the study was to assess the clinical utility of a liquid-based cytology system on cervicovaginal screening in a clinical commercial laboratory. Twenty-six thousand, one hundred and seventy eight cervicovaginal specimens were prepared by the Liqui-PREP (LGM International Inc., Ft. Lauderdale, FL) with a direct-to-vial comparison to 218,548 cases of the conventional direct smear from August 2005 through December 2005. Biopsy data was obtained to confirm the sensitivity for each method. Liqui-PREP showed a marked increase in HSIL+ detection compared to the conventional smear ( P = 0.001). The rate of LSIL and AGC detection was higher with Liqui-PREP ( P equals; 0.001 for both). The percentage of ASCUS specimens was higher than with conventional smear due to cleaner slides and easier detection of suspicious cells. The WNL rate was lower for Liqui- PREP ( P = 0.001) consistent with increased HSIL+ and ASCUS. The unsatisfactory rate was lower for Liqui-PREP ( P = 0.017). The histological predictive value of Liqui-PREP was slightly higher than the conventional smear (94.1% versus 89.9%). The Liqui-PREP system similar to other reported LBC technologies shows an increased detection of squamous intraepithelial lesions, and gives higher-quality slides for interpretation than the conventional smear. Histological results confirm that this increase in cytological findings are clinically significant. LGM's new LBC technology is a more sensitive screening tool when compared with the conventional smear.

Evaluation of p16INK4a, minichromosome maintenance protein 2, DNA topoisomerase II α, ProE X C, and p16INK4a/ProE X C in cervical squamous intraepithelial lesions

p16INK4a has been shown to be overexpressed in nearly all high-grade squamous intraepithelial lesions (HSILs). Other cell-cycle regulators, such as minichromosome maintenance protein 2 (MCM2), DNA topoisomerase IIalpha (TOP IIA), and ProE(X) C (a cocktail of MCM2 and TOP IIA), have also demonstrated some value in identifying squamous intraepithelial lesions. Data on direct comparison of those cell regulatory proteins in the detection of squamous intraepithelial lesions, with a focus on low-grade squamous intraepithelial lesions (LSILs), are limited. We immunohistochemically evaluated the diagnostic value of p16, MCM2, TOP IIA, ProE(X) C, and a cocktail of p16 and ProE(X) C in 62 cervical biopsy specimens, including 14 cases of benign squamous mucosa (group 1), 34 cases of LSILs (group 2), and 14 cases of HSILs (group 3). The staining intensity and distribution were recorded. The results demonstrated that positive staining for p16 and the p16/ProE(X) C was observed in 100% of cases in group 3, whereas 79%, 86%, and 79% of cases were positive for CM2, TOP IIA, and ProE(X) C, respectively. ProE(X) C and the p16/ProE(X) C showed positive staining in 94% and 100% of cases in group 2, respectively. In contrast, immunoreactivity for p16, MCM2, and TOP IIA was detected in only 76% of cases in group 2. Importantly, all 8 p16-negative cases in group 2 were positive for p16/ProE(X) C (P = .003). Our data indicate that (1) p16 is a more sensitive and specific marker for identifying HSILs; (2) ProE(X) C is a better marker for the detection of LSILs; and (3) p16/ProE(X) C provides the highest diagnostic value for the detection of both HSILs and LSILs.