Natural History Of Cervical Intraepithelial Neoplasia Research Articles

Cervical intraepithelial neoplasia and cervical cytology in pregnancy.

Cervical cancer screening during pregnancy presents unique challenges for cytologic interpretation. This review focuses on pregnancy-associated cytomorphological changes and their impact on diagnosis of cervical intraepithelial neoplasia (CIN) and cervical cancer. Pregnancy-induced alterations include navicular cells, hyperplastic endocervical cells, immature metaplastic cells, and occasional decidual cells or trophoblasts. These changes can mimic abnormalities such as koilocytosis, adenocarcinoma in situ, and high-grade squamous intraepithelial lesions, potentially leading to misdiagnosis. Careful attention to nuclear features and awareness of pregnancy-related changes are crucial for correct interpretation. The natural history of CIN during pregnancy shows higher regression rates, particularly for CIN 2, with minimal risk of progression. Management of abnormal cytology follows modified risk-based guidelines to avoid invasive procedures, with treatment typically deferred until postpartum. The findings reported in this review emphasize the importance of considering pregnancy status in cytological interpretation, highlight potential problems, and provide guidance on differentiating benign pregnancy-related changes from true abnormalities. Understanding these nuances is essential for accurate diagnosis and proper management of cervical abnormalities in pregnant women.

Influence of age on histologic outcome of cervical intraepithelial neoplasia during observational management: results from large cohort, systematic review, meta-analysis

Aim of this study was to investigate the histologic outcome of cervical intraepithelial neoplasia (CIN) during observational management. Consecutive women with histologically verified CIN and observational management were included. Histologic findings of initial and follow-up visits were collected and persistence, progression and regression rates at end of observational period were assessed. Uni- and multivariate analyses were performed. A systematic review of the literature and meta-analysis was performed. In 783 women CIN I, II, and III was diagnosed by colposcopically guided biopsy in 42.5%, 26.6% and 30.9%, respectively. Younger patients had higher rates of regression (p < 0.001) and complete remission (< 0.001) and lower rates of progression (p = 0.003). Among women aged < 25, 25 < 30, 30 < 35, 35 < 40 years, and > 40 years, regression rates were 44.7%, 33.7%, 30.9%, 27.3%, and 24.9%, respectively. Pooled analysis of published data showed similar results. Multivariable analysis showed that with each five years of age, the odds for regression reduced by 21% (p < 0.001) independently of CIN grade (p < 0.001), and presence of HPV high-risk infection (p < 0.001). Patient’s age has a considerable influence on the natural history of CIN – independent of CIN grade and HPV high-risk infection. Observational management should be considered for selected young patients with CIN.

Reproducibility of cervical intraepithelial neoplasia diagnosis on histological review of cervical punch biopsies from a visual inspection with acetic acid and HPV detection-based screening program

ObjectiveTo assess the reproducibility of cervical intraepithelial neoplasia (CIN) diagnosis in a visual inspection with acetic acid (VIA) and HPV detection-based screening program, and to correlate CIN diagnosis with oncogenic HPV status. MethodsA total of 9630 women were screened by VIA and high-risk HPV detection at community outreach clinics in India between June 2011 and June 2012. Biopsies obtained from women who were positive on either test were reviewed by two pathologists blinded to the histological diagnoses originally made by pathologists working at the Chittaranjan National Cancer Institute. ResultsThe interobserver agreement between the pathologists’ diagnoses and the diagnoses made by the expert reviewers on 424 slides was fair (kappa=0.26). There was a distinct difference in agreement in detecting CIN 2 (kappa=0.21) and detecting CIN 3 (kappa=0.74). The overall agreement in diagnosis improved when the slides obtained from the HPV-positive women were considered (kappa=0.5). Almost half of the discordant CIN 2 cases were high-risk HPV negative. ConclusionDiagnosis of CIN 2 is poorly reproducible. The natural history of CIN 2 lesions is more similar to CIN 1 than CIN 3; it is therefore necessary to re-evaluate whether to consider CIN 2 lesions as high-grade squamous intraepithelial lesions with CIN 3, as in the Bethesda system of classification.

Outcomes After Management of Young Women With Cervical Intraepithelial Neoplasia 2 With a 6-Month Observation Protocol

Recommendations regarding treatment of cervical intraepithelial neoplasia (CIN) 2 in women have evolved over the years: young women with CIN 2 may be offered observation with Pap smears and colposcopy every 6 months instead of immediate excision or ablation of disease. The purpose of this study was to observe patient follow-up during the initiation of this management protocol for young women with CIN 2. This was a retrospective review of clinical outcomes of women younger than 30 years with CIN 2 on index biopsy and planned follow-up at UNC between July 2009 and August 2010. A chart review for clinical variables, follow-up visits, and progression of disease was conducted. Primary analysis determined the rate of follow-up and pathology at 6 months. Secondary analysis investigated risk factors for incomplete follow-up. Seventy women met inclusion criteria; 46 were managed with observation. Twenty-eight (60.8%; 28/46) women completed a follow-up visit. Demographic and clinical variables did not reach statistical significance in predicting the likelihood of completion of a follow-up visit, although there was a trend toward greater follow-up in employed patients (odds ratio = 5.25, 95% confidence interval = 0.84-34.78). Approximately half (52.4%; 11/21) of women with a completed cervical biopsy demonstrated regression of disease during the study period. On the basis of these data, follow-up in this population was unpredictable based on basic demographic or clinical factors that we often use to judge likelihood of compliance with medical recommendations. The percentage of patients with regression at follow-up was as expected from the natural history of CIN 2.

Recent developments in HIV and women's health

Key content In the UK, the proportion of HIV‐positive pregnant women diagnosed before delivery is around 95%. The benefits of highly active antiretroviral therapy (HAART) in reducing mother‐to‐child transmission are undisputed; however, there are potentially adverse effects on maternal and fetal/neonatal health. Vaginal delivery may be considered for HIV‐positive pregnant women with undetectable viral loads who are on HAART. Hormonal contraception can be affected by drug–drug interactions with HAART or nonantiretroviral medication that HIV‐positive women may be taking. Although HAART can alter the natural history of cervical intraepithelial neoplasia (CIN), annual cervical cytology is still recommended. Learning objectives To be aware of the different types of HAART, their use and associated maternal, fetal and neonatal toxicities. To be able to critically evaluate the place of prelabour elective caesarean section in light of recent developments in viral load testing and HAART. To be aware of potential drug–drug interactions that can reduce the efficacy of hormonal contraception in HIV‐positive women. To appreciate the potential impact of HAART and the recently developed human papillomavirus vaccines on the natural history of CIN in HIV‐positive women. To know where to find up‐to‐date information on drug–drug interactions and clinical vaccine trials relating to HIV. Ethical issues Clear communication about the potential risks and benefits of strategies to reduce mother‐to‐child transmission is critical to enable HIV‐positive pregnant women to reach informed decisions about their care. Please cite this article as: Kelly B, Morrison J, Hurley P. Recent developments in HIV and women's health. The Obstetrician &amp; Gynaecologist 2008;10:42–48.

Cervical human papillomavirus infection and cervical intraepithelial neoplasia in women positive for human immunodeficiency virus in the era of highly active antiretroviral therapy.

Human papillomavirus (HPV) has been strongly implicated in the pathogenesis of cervical intraepithelial neoplasia (CIN) and cervical cancer. Women who are positive for the human immunodeficiency virus (HIV) have been shown to be at increased risk for cervicovaginal HPV infection and CIN, and cervical cancer is an acquired immunodeficiency syndrome-defining illness. The purpose of this review is to summarize recent studies of cervical HPV infection and CIN in HIV-positive women and to describe the effect of highly active antiretroviral therapy (HAART) on the course of CIN. HIV-positive women have a higher prevalence of cervical HPV infection than HIV-negative women, and HPV infection is more persistent in the HIV-positive population. The incidence of high-grade CIN is increased in HIV-positive women. HAART has not been shown to affect HPV detection, and data on its effect on the natural history of CIN are mixed. Some studies show no effect of HAART on the natural history of CIN, and others show a statistically significant but modest beneficial effect. Cervical HPV infection and CIN are clearly increased in HIV-positive women when compared with risk-matched HIV-negative women. HAART appears to have limited ability to clear HPV infection and induce regression of CIN in HIV-positive women. Combined with the high prevalence of cervical HPV infection and CIN, current data suggest that CIN should be aggressively sought and treated in HIV-positive women, including those who have responded well to HAART with good HIV viral load suppression and increasing CD4+ levels.

Absence of papillomavirus DNA in normal tissue adjacent to most cervical intraepithelial neoplasms

To determine if human papillomavirus (HPV) DNA is present in the normal mucosa adjacent to cervical intraepithelial neoplasia (CIN). Serial sections of 28 CIN lesions were studied. Lesional and normal epithelia and stroma were microdissected; the DNA was extracted and amplified by polymerase chain reaction (PCR) using primers designed to amplify both HPV late (L1) and human beta-globin sequences. Human papillomavirus was typed by restriction fragment length polymorphism analysis following digestion of PCR products. Twenty-five of 28 (89%) lesional epithelia scored positive for HPV nucleic acids. In' four of 25 (16%) HPV-positives, the normal squamous epithelium scored positive for HPV nucleic acids, two of which (8%) also scored positive in the stroma. Repeat microdissection and PCR analysis of three of these cases was performed and all were negative in both normal epithelium and stroma, suggesting laboratory contamination. Human papillomavirus nucleic acids are present uncommonly in normal-appearing squamous epithelium adjacent to CIN. This does not exclude occult infection in the natural history of CIN but indicates that when lesions develop, occult infection is not normally maintained in the normal mucosa. This is consistent with the low recurrence rates following ablation as well as low indices of HPV positivity in normal cervices during follow-up. This finding should be taken into consideration when counseling patients and is relevant to the concept of HPV testing during follow-up after cone biopsy.