Persistent High-grade Squamous Intraepithelial Lesions Research Articles

Risk Factor Analysis of Persistent High-Grade Squamous Intraepithelial Lesion After Loop Electrosurgical Excision Procedure Conization.

The aim of the study was to analyze the clinical outcomes of high-grade squamous intraepithelial lesion (HSIL) 6 months after loop electrosurgical excision procedure (LEEP). We explored the risk factors of persistent cervical HSIL after LEEP and evaluated the methods of follow-up. This retrospective study included women who underwent a LEEP and had a diagnosis of HSIL in their LEEP specimen during 2011 to 2015. The purpose was to determine the risk factors among these women for having persistent HSIL disease at their 6-month follow-up visit. At their follow-up visit, each woman underwent cervical cytology and high-risk human papilloma virus (hrHPV) testing, colposcopy-directed punch biopsy, and/or endocervical curettage. A total of 3582 women were enrolled. There were 9 cases invasive cervical cancer found and 101 women had persistent HSIL. The persistence rate was higher in women 50 years or older. The circumference, length, and width of LEEP specimens did not differ statistically between the persistent and nonpersistent group. The persistence rate among women with positive LEEP specimen margins was higher than among women with negative margins. Positive endocervical margins were associated with a higher rate of persistence than positive ectocervical margins. Multivariate logistic analysis showed that age, positive margins, abnormal cytology, and positive hrHPV during follow-up were all independent risk factors for persistent HSIL lesions. Being 50 years or older, positive margins, particularly endocervical margins, and having abnormal cytology and positive hrHPV testing during follow-up were risk factors for persistent HSIL lesions after LEEP conization. Colposcopy plays an indispensable role in the diagnosis of persistent HSIL and progression.

The Role of Cytology in the 21st Century: The Integration of Cells and Molecules

Objectives: Cervical cancer screening test performance has been hampered by either a lack of sensitivity in Pap cytology or a lack of specificity of human papillomavirus (HPV) testing. This is disturbing for patients and a cause of high costs for health care providers. Study Design: The identification of p16^INK4a as a specific marker for the neoplastic transformation of cervical squamous epithelial cells by HPVs allows the identification of HPV-transformed cells in cytopathology specimens. Results: When compared to molecular HPV tests for triaging minor cytologic atypia, such as atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesions, the immunochemical detection of dual p16^INK4a/Ki-67-stained cells demonstrates a significantly improved specificity with good relative sensitivity. Conclusions: HPV testing has shown earlier detection of persistent high-grade squamous intraepithelial lesions (HSIL) compared to cytology and is more effective in preventing invasive cervical cancer. The next challenge for the HPV primary screening program is to find the best method(s) for selecting, among HPV-positive women, those patients in need of immediate colposcopy because they are at a higher risk of developing a precancerous lesion. An HSIL cytology result and/or dual p16/Ki-67 staining could be the best candidates, but further randomized studies are required before these approaches can be used in routine practice.

Multivariate analysis of risk factors for the persistence of high-grade squamous intraepithelial lesions following loop electrosurgical excision procedure.

To evaluate risk factors related to the persistence of high-grade squamous intraepithelial lesions (HSILs) following loop electrosurgical excision procedure (LEEP). The present prospective, observational study evaluated a convenience sample of participants with HSILs who were treated using LEEP between January 7, 2003 and December 30, 2011. Participants were evaluated 6months and 1year after treatment. Potential risk factors included in multivariate analyses were HIV co-infection, involved margins, multicentric lesions, smoking, and use of hormonal contraception. The present study enrolled 307 participants. At 1year, 250 (81.4%) participants were free from lesions, 30 (9.8%) had low-grade squamous intraepithelial lesions, 26 (8.5%) had persistent HSILs, and 1 (0.3%) had developed invasive carcinoma. The risk of lesions persisting at 1year after LEEP was increased by HIV infection (P=0.003), involved margins (P=0.05), and smoking (P=0.02). The presence of multicentric lesions (P=0.73) and the use of hormonal contraception (P=0.99) did not increase the risk of lesion persistence. The risk of HSIL persistence was increased by the presence of involved margins (relative risk 3.25; 95% confidence interval 1.55-6.80; P=0.001). The presence of involved margins was the only variable that increased the risk of HSIL persistence after LEEP, increasing the risk of patients requiring further treatment.

Laser capture microdissection as a tool to evaluate human papillomavirus genotyping and methylation as biomarkers of persistence and progression of anal lesions

IntroductionAnal squamous cell carcinoma is preceded by persistent infection with high-risk human papillomavirus (HPV) and the cancer precursor, high-grade squamous intraepithelial lesion (HSIL). Detection of specific HPV genotypes and HPV-related...

O10.5 Human Papillomavirus (HPV) Genotypes Associated with Persistent HSIL Isolated by Laser Capture Microdissection

BackgroundAnal squamous cell carcinoma (ASCC) is preceded by persistent high-grade squamous intraepithelial lesion (HSIL). A small proportion of HSIL will progress to ASCC; estimates in men who have sex with...

Risk of persistent high-grade squamous intraepithelial lesion after electrosurgical excisional treatment with positive margins: a meta-analysis.

Even if precursor lesions of cervical cancer are properly treated, there is a risk of persistence or recurrence. The aim here was to quantify the risks of persistence of high-grade intraepithelial squamous lesions, one and two years after cervical electrosurgical excisional treatment with positive margins. Systematic review of the literature and meta-analysis at Instituto Fernandes Figueira. This meta-analysis was on studies published between January 1989 and July 2009 that were identified in Medline, Scopus, Embase, Cochrane, SciELO, Lilacs, Adolec, Medcarib, Paho, Wholis, Popline, ISI Web of Science and Sigle. Articles were selected if they were cohort studies on electrosurgical excisional treatment of high-grade squamous intraepithelial lesions with a minimum follow-up of one year, a histopathological outcome of persistence of these lesions and a small risk of bias. The search identified 7,066 articles and another 21 in the reference lists of these papers. After applying the selection and exclusion criteria, only four articles were found to have extractable data. The risk of persistence of high-grade intraepithelial lesions after one year was 11.36 times greater (95% confidence interval, CI: 5.529-23.379, P < 0.0001) in patients with positive margins and after two years, was four times greater (95% CI: 0.996-16.164), although without statistical significance. This meta-analysis confirms the importance of positive margins as an indicator of incomplete treatment after the first year of follow-up and highlights the need for appropriately chosen electrosurgical techniques based on disease location and extent, with close surveillance of these patients.

Testing for high risk human papilloma virus in the initial follow‐up of women treated for high‐grade squamous intraepithelial lesions

The follow-up schedule of women who have undergone treatment for high grade squamous intraepithelial lesions (HSIL) is a crucial part of the cervical screening programme. The ability to detect residual disease or early recurrence enables the provision of timely secondary intervention. The aim of this study was to determine the prevalence of High Risk HPV and cytological abnormalities at first follow-up visit post treatment. The feasibility, safety and cost benefit of omitting routine colposcopy as a first line investigation were evaluated. A total of 100 women with histologically confirmed and treated HSIL were recruited prior to first follow-up visit. Colposcopic assessment, cervical cytology using LBC and HR HPV testing was carried out on all women. In all, 75% of the study group had both a negative HR HPV test and a normal cervical cytology at first follow-up visit. Mean time interval to first follow-up was 9 months. The rate of residual/recurrent high-grade disease within this cohort was 4% followed up to 18 months post treatment. HR HPV had a sensitivity of 100% to detect persistent HSIL. High-risk human papilloma virus testing in combination with cytology at first follow-up visit in women treated for HSIL has a very high sensitivity and negative predictive value. Colposcopy does not improve specificity in this cohort and could be omitted in patients who have a negative smear and HPV test.

Combined p53 and Retinoblastoma Protein Detection Identifies Persistent and Regressive Cervical High-Grade Squamous Intraepithelial Lesions

Most cervical high-grade squamous intraepithelial lesions (HSILs) persist, but approximately one third regress (ie, no HSIL in follow-up biopsies). To identify factors related to histologic proven persistence or regression. Twenty-eight small histologic (marker) biopsies with adequate follow-up were analyzed for human papillomavirus (HPV) genotypes and different immunoquantitative proliferation, cell cycle regulation, and differentiation markers. All cases had a biopsy-interval between the marker and first follow-up biopsy of at least 100 days (median, 8.2 months; range, 3.4-22.5 months). Follow-up was classified as regression or persistence. All lesions were high-risk (hr) HPV and p16 positive, 63% for HPV-16 or HPV-16 mixed with other hr genotypes, while 37% had other hrHPV types. The marker biopsies of the persistent HSILs had lower p53 and retinoblastoma protein (pRb) detected in the deep half of the epithelium (P = 0.001 and 0.02, respectively) than nonpersistent HSILs. The degree of positivity of p16, Ki-67, cyclin D1, lesion extent, positivity of the resection margins, and patient age were all unrelated to persistence or regression. Lesions with HPV-16 or mixed-16 genotypes had a significantly lower percentage of pRb (P = 0.02), p53 (P = 0.02), and cyclin D (P = 0.04) positive nuclei in the deep epithelial layers. In agreement with this, type-16 positive HSILs had a lower regression percentage than those with other HPV types, but the difference was not significant. HSILs with combined negativity/low positivity for p53 and pRb protein in small histologic biopsies are highly likely to persist, contrasting those in which one of these cell cycle regulators is strongly positive (p53 > 15%; pRb > 40%).

Infrared Coagulator™: A Useful Tool for Treating Anal Squamous Intraepithelial Lesions

The incidence of invasive anal squamous carcinoma in men who have sex with men is rising, particularly in those with human immunodeficiency virus. As in the cervix the high-grade squamous intraepithelial lesion is thought to be an invasive squamous cell carcinoma precursor. Cervical high-grade squamous intraepithelial lesions are treated by removing the squamocolumnar transition zone. This is not possible in the anus, where treatment is often surgical and is accompanied by significant pain and morbidity. Better office-based techniques to treat anal high-grade squamous intraepithelial lesions are needed. We employed the infrared coagulator in an office setting to ablate high-grade squamous intraepithelial lesions. A retrospective review of medical records was performed on 68 human immunodeficiency virus-positive men who have sex with men who underwent infrared coagulator ablation of biopsy-proven high-grade dysplasia from the time we began using the procedure in 1999. All patients have had at least six months of follow-up. Procedures were performed with local anesthesia on patients with discrete high-grade squamous intraepithelial lesions. Follow-up consisted of anal cytology with high-resolution anoscopy and biopsy of suspicious areas every three to six months. New or recurrent high-grade dysplasia was retreated. Patients with circumferential or bulky disease were treated in the operating room and were excluded from the study. Altogether, 68 patients met the enrollment criteria. The median patient age was 41 years (range 29-62 years). A total of 165 lesions were treated (mean 1.6 lesions, range 1-5) and only 46 (28 percent) persisted. However, 44 patients (65 percent) developed a new or persistent high-grade squamous intraepithelial lesion within a median time of 217 days (range 27-566 days) after infrared coagulation. The remaining 24 patients (35 percent) were free of high-grade dysplasia for a median of 413 days (range 162-1313 days) after infrared coagulation. When patients were treated a second or third time, the incidence of new or persistent high-grade dysplasia dropped to 58 percent and 40 percent, respectively. The probability of curing a retreated lesion was 72 percent. Using generalized estimating equations, the incidence of high-grade dysplasia decreased with repeated infrared coagulator treatments. No patient developed squamous-cell carcinoma, had a serious adverse event, or developed anal stenosis. The infrared coagulator is a safe, office-based modality for treating anal high-grade squamous intraepithelial lesion in human immunodeficiency virus-positive men who have sex with men. Successive treatments led to decreased recurrence rates.

Histopathological variables predicting high-grade squamous intraepithelial lesions after large-loop excision of the transformation zone.

Our aim was to determine whether histopathological variables predict persistent high-grade squamous intraepithelial lesions (HGSIL) after large-loop excision of the transformation zone (LLETZ). All patients with cervical intraepithelial neoplasia (CIN) grade 2 or 3 on a LLETZ specimen with at least one follow-up Papanicolaou (Pap) test were identified. Histopathological variables were evaluated for the potential to predict HGSIL on a follow-up Pap test. Variables examined included endocervical margin status, ectocervical margin status, endocervical curettage (ECC) result, presence or absence of endocervical glandular involvement, and presence or absence of koilocytosis. Two hundred and nineteen cases were identified. A follow-up Pap test showed HGSIL in 16 patients (7.3%). Of the histopathological variables studied, only a positive ECC at the time of LLETZ conization predicted HGSIL on follow-up cytology (p =.0002). Endocervical margin status, ectocervical margin status, presence or absence of glandular involvement, and presence or absence of koilocytosis were not associated significantly with HGSIL at follow-up. Most histopathological factors from LLETZ conization do not predict reliably the presence of HGSIL at the time of follow-up Pap test. A positive ECC at the time of LLETZ, however, may predict those patients destined to have persistence or recurrence. These findings suggest that conservative follow-up is warranted after LLETZ conization.