High-grade Preinvasive Lesions Research Articles

Cold Knife Versus Carbon Dioxide for the Treatment of Preinvasive Cervical Lesion.

Background and Objectives: Cervical cancer (CC) represents a significant health concern worldwide, particularly for younger women. Cold knife (CK) conization and carbon dioxide (CO2) laser conization are two techniques commonly used to remove pre-invasive lesions, offering a potential curative intent in cases of incidental diagnosis of CC. This study aimed to assess the clinical implications and pathological outcomes of CK vs. CO2 laser conization for pre-invasive lesions. Materials and Methods: We retrospectively analyzed women who underwent CO2 or CK conization for high-grade preinvasive lesions (CIN2/3, CIS and AIS) between 2010 and 2022. Patient demographics, surgical details and pathological outcomes were collected. Pregnancy outcomes, including composite adverse obstetric rates, and oncological follow-up data, were also obtained. Results: In all, 1270 women were included; of them, 1225 (96.5%) underwent CO2, and 45 (3.5%) underwent CK conization. Overall, the rate of positive endocervical or deep margins was lower with CO2 laser compared to CK (4.3% vs. 13.3%, p = 0.015). Incidental CC was diagnosed in 56 (4.4%) patients, with 35 (62.5%) squamous and 21 (46.6%) adenocarcinomas. In a multivariate regression model, the relative risk for positive endocervical or deep margins is significantly greater in cases of incidental diagnosis of CC (p < 0.01). In cases of incidental diagnosis of CC, we found that the probabilities of having either positive endocervical or deep margins after CO2 laser or CK conization are similar, with a higher risk in case of adenocarcinoma lesion. Among women with CC, 42 (75%) opted for radical treatment, while 14 (25%) underwent a follow-up. Only one woman (7.1%) in the follow-up group, who had undergone CK conization, experienced a composite adverse obstetric outcome. No recurrences were observed after a median follow-up of 53 months. Conclusions: CO2 laser conization achieved a lower positive margin rate overall. CK and CO2 conization appear to be equivalent oncological options for incidental CC.

Immune evasion before tumour invasion in early lung squamous carcinogenesis

Early detection and treatment are critical for improving the outcome of patients with cancer1. Understanding the largely uncharted biology of carcinogenesis requires deciphering molecular processes in premalignant lesions, and revealing the determinants of the intralesional immune reaction during cancer development. The adaptive immune response within tumours has previously been shown to be strongest at the earliest stage of carcinoma2,3. Here we show that immune activation and immune escape occur before tumour invasion, and reveal the relevant immune biomarkers of the pre-invasive stages of carcinogenesis in the lung. We used gene-expression profiling and multispectral imaging to analyse a dataset of 9 morphological stages of the development of lung squamous cell carcinoma, which includes 122 well-annotated biopsies from 77 patients. We identified evolutionary trajectories of cancer and immune pathways that comprise (1) a linear increase in proliferation and DNA repair from normal to canceroustissue; (2) a transitory increase of metabolism and early immune sensing, through the activation of resident immune cells, in low-grade pre-invasive lesions; (3) the activation of immune responses and immune escape through immune checkpoints and suppressive interleukins from high-grade pre-invasive lesions; and, ultimately, (4) the activation of the epithelial-mesenchymal transition in the invasive stage of cancer. We propose that carcinogenesis in the lung involves a dynamic co-evolution of pre-invasive bronchial cells and the immune response. These findings highlight the need to develop immune biomarkers for early detection as well as immunotherapy-based chemopreventive approaches for individuals who are at high risk of developing lung cancer.

Low Prevalence of High-Grade Lesions Detected With Autofluorescence Bronchoscopy in the Setting of Lung Cancer Screening in the Pan-Canadian Lung Cancer Screening Study

Lung cancer screening with low-dose CT (LDCT) scan has been demonstrated to reduce lung cancer mortality. Preliminary reports suggested that up to 20%of lung cancers may be CT scan occult but detectable by autofluorescence bronchoscopy (AFB). We evaluated the prevalence of CT scan occult, invasive, and high-grade preinvasive lesions in high-risk participants undergoing screening for lung cancer. The first 1,300 participants from seven centers in the Pan-Canadian Early Detection of Lung Cancer Study who had≥ 2%lung cancer risk over 5 years were invited tohave an AFB in addition to a LDCT scan. We determined the prevalence of CT scan and AFB abnormalities and analyzed the association between selected predictor variables and preinvasive lesions plus invasive cancer. A total of 776 endobronchial biopsies were performed in 333 of 1,300 (25.6%) participants. Dysplastic or higher-grade lesions were detected in 5.3%of the participants (n= 68; mild dysplasia: n= 36, moderate dysplasia: n= 25, severe dysplasia: n= 3, carcinoma insitu [CIS]: n= 1, and carcinoma: n= 4). Only one typical carcinoid tumor and one CIS lesion were detected by AFB alone, for a rate of CT scan occult cancer of 0.15%(95%CI, 0.0%-0.6%). Fifty-six prevalence lung cancers were detected by LDCT scan (4.3%). The only independent risk factors for finding of dysplasia or CIS on AFB were smoking duration (OR, 1.05; 95%CI, 1.02-1.07) and FEV1 percent predicted (OR, 0.99; 95%CI, 0.98-0.99). The addition of AFB to LDCT scan in a high lung cancer risk cohort detected too few CT occult cancers (0.15%) to justify its incorporation into a lung cancer screening program. ClinicalTrials.gov; No.: NCT00751660; URL: www.clinicaltrials.gov.

Implications of Post-LLETZ “Treatment Failure” for Further Management of HIV-Infected Women

Background. Since the preconisation presence of high-risk human papillomavirus (HR-HPV) is the main determinant of the risk of progression of preinvasive lesions; the state of the excision margins could be of less importance. Relatively little is known about the effect of human immunodeficiency virus (HIV) infection on the relation between the states of the excision margins. Methods. We compared 120 HIV-infected and 139 HIV-uninfected women who underwent a hysterectomy after large loop excision of the transformation zone (LLETZ) for abnormal Pap smear. Results. The excision margins had been reported negative in 21.7% of infected and 7.8% of uninfected cases (P=0.03). Three (11.5%) of 26 negative margins in HIV-infected and 2 (18.2) out of HIV-uninfected cases were falsely negative as evidenced on hysterectomy specimens (P=0.73). The persistence rate of the initial lesion was similar in both groups (P=0.20). The persistence rate with highly active antiretroviral treatment (HAART) was similar to untreated patients (P=0.20). The progression rate from low-grade to high-grade preinvasive lesions was higher in HIV-infected than HIV-uninfected women (P=0.027). Conclusion. HIV-infected women with incomplete excision margins after LLETZ are at higher risk of progression of residual preneoplastic lesions.

Cervical preneoplasia biomarkers: a conundrum for the community based gynecologic surgical pathologist

The integration of high-risk (HR) human papillomavirus (HPV) in the cell genome is an essential step in the oncogenic pathway of lower ano-genital HPV-related squamous preinvasive and invasive lesions. The expression of HR-HPV surrogate biomarkers of HR-HPV integration by immunohistocytochemistry (IHC) serves as a diagnostic and/or a prognostic tool of cervical preinvasive lesions. IHC is claimed to decrease the interobserver variability in the diagnosis of histomorphologically equivocal lesions, and to be helpful in evaluating the potentiality of regression, persistence or progression. The most common biomarkers used in cervical pathology are p16INK4a, Ki-67, the HPV capsid L1 antigen, and ProEXc. Critical review of the literature shows a great variability in the diagnostic accuracy, risk evaluation, and relative distribution of these biomarkers in low and high grade preinvasive lesions. Review of the literature suggests that currently dual IHC with p16 and L1 provide the best diagnostic and prognostic evaluation of lesions diagnosed histomorphologically as low and high-grade.

Abnormal colposcopic images in patients with preinvasive cervical lesions

Introduction: The objective of the study was to determine frequency and to compare frequency of the abnormal colposcopic images in patients with low and high grade pre-invasive lesions of cervix.Methods: Study includes 259 patients, whom colposcopic and cytological examination of cervix was done. The experimental group of patients consisted of patents with pre-invasive low grade squamousintraepithelial lesion (LSIL) and high grade squamous intraepithelial lesion (HSIL), and the control group consisted of patients without cervical intraepithelial neoplasia (CIN).Results: In comparison to the total number of satisfactory fi ndings (N=259), pathological findings were registered in N=113 (43.6 %) and abnormal colposcopic fi ndings in N=128 (49.4%). The study did notinclude patients with unsatisfactory fi nding N=22 (8.5%). Abnormal colposcopic image is present most frequently in older patients but there are no statistically important difference between age categories(Pearson Chi-Square 0.47, df -3, p=0.923). Frequency of abnormal colposcopic fi ndings (N=128) is the biggest in pathological cytological (N=113) and HSIL 58 (45.3%), LSIL 36 (28.1%). There is statisticallysignifi cant difference in frequency of abnormal colposcopic images in patients with low-grade in comparison to patients with high-grade pre-invasive cervix lesions (Chi-Square test, Pearson Chi-Square 117.14,df-12 p&lt;0.0001).Conclusion: Thanks to characteristic colposcopic images, abnormal epithelium is successfully recognized, but the severity grade of intraepithelial lesion cannot be determined.

The impact of human immunodeficiency virus infection on cervical preinvasive and invasive neoplasia in South Africa.

Objectives:Sub-Saharan Africa is at the epicentre of the human immunodeficiency virus (HIV) epidemic and has the highest incidence of invasive cervical cancer (ICC) in the world. Access to highly active antiretroviral treatment (HAART) in South Africa is still limited and provided only to nonpregnant women with a CD4+ T-cell count <200 μg/L. We evaluated the relative distribution of cervical preinvasive and invasive neoplasia among HIV-infected (treated or not) and uninfected women in the Limpopo Province of South Africa.Methods:We compared the consecutive biopsy-diagnosed cervical pathology of 1,023 HIV-infected and 1,023 uninfected women. We investigated the influence of the CD4+ T-cell count and of HAART on the relative distribution of cervical pathology.Results:There was a significantly higher proportion of cervical intraepithelial neoplasia (CIN)1 (P = 0.012) and 2 (P = 0.01) but a lower proportion of ICC (P = 0.015) among HIV-infected women. Patients on HAART had less CIN1 (P = 0.018), 2 (P = 0.18) and ICC (P = 0.019) that their untreated counterparts. The mean CD4 count was similar regardless of cervical lesions and HAART or no treatment.Conclusion:Our data support the concept that HIV-infected women exhibit a higher rate of high-grade preinvasive lesions than uninfected controls. However, they have a significantly lower rate of ICC as compared with uninfected counterparts. The inclusion of ICC among acquired immune deficiency syndrome-defining illnesses is questionable.

Can quantifying free-circulating DNA in plasma be used to identify subjects with high-grade pre-invasive endobronchial lesions?

Increased concentrations of free-circulating plasma DNA (cpDNA) are observed in patients with invasive cancer, including lung cancer. Whether cpDNA levels are elevated in subjects with high-grade pre-invasive lesions of lung squamous cell carcinoma (SqCC) and whether its detection may be of value for identifying subjects at the highest risk of developing lung SqCC is currently unknown. The present study assessed cpDNA levels in subjects with high- and low-grade pre-invasive squamous endobronchial lesions relative to patients with clinically overt lung SqCC and healthy controls using real-time quantitative PCR methodology. The median cpDNA levels of the patients with invasive lung SqCC (n=16) were significantly higher compared with those of the healthy controls (n=16; P<0.01), whereas the cpDNA levels in the subjects with pre-invasive lesions (n=20) did not differ from those of the controls (P=0.29). The cpDNA levels in subjects with high-grade pre-invasive lesions were highly similar to those diagnosed with low-grade pre-invasive lesions (P=0.85). Our data suggest that cpDNA levels are not increased during the pre-invasive stages of lung squamous carcinogenesis.

Epidemiologia e impacto econômico do câncer de colo de útero no Estado de Roraima: a perspectiva do SUS

to evaluate the incidence and direct economic impact of cervical cancer (CC) in Roraima, in 2009, and to analyze the epidemiological profile of patients with this disease. the histopathologic reports issued in Roraima in 2009 were reviewed, as were hospital records of female patients under treatment for cancer. Clinical data and medical procedures related to CC were recorded. CC carriers were treated under expenses of the public Brazilian health system (SUS) in Roraima underwent an interview dealing with socio-economic topics. we registered 90 cases of CC and high grade pre-invasive lesions. Roraima has the highest incidence of CC of Brazil (46.21 cases/100,000 women), which is 3 times higher than that of breast cancer, comparable to low-income developing countries. The epidemiological profile shows patients with economic deprivation, social disadvantage, low education, early first intercourse (mean age is 13.8 years), and high parity (medium of 5.5 gestations). Among the patients included in this report, 71.7% had never been submited to a Pap smear, and ignorance about it was the main reported reason (47.4%). As a public health problem, the management of CC generates direct annual expenditures of more than R$ 600,000, with an average cost per patient of R$ 8,711. CC is the most common cancer among women from Roraima, and represents a serious public health problem in Roraima. Its high economic impact favors the implementation of preventive strategies from the standpoint of cost-effectiveness. The profile of patients reveals the ineffectiveness of preventive services in reaching patients with a socio-economic exclusion profile at high risk for cervical cancer.

Abstract 2727: Predicting lung cancer risk based on a novel proteomic signature of bronchial lesions

Abstract A biomarker signature to identify individuals at-risk for lung cancer would be of great clinical value. We hypothesized that the bronchial epithelium expresses a subset of proteins that once increased confer an elevated risk for lung cancer. We have therefore developed a proteomic approach to assess the risk for lung cancer. From our previous studies, we selected 11 matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) features to distinguish normal bronchial epithelium and low grade preinvasive lesions from high grade preinvasive lesions and invasive lung tumors. We tested this signature in an independent validation set consisting of bronchial specimens from 60 patients. The prediction accuracy was 78% with 73% sensitivity and 81% specificity. There was a 19-fold increased risk of having lung cancer for individuals with a signature intensity above the third quartile (95% CI, 5.65-64.81). We identified 10 of the 11 features corresponding to 7 proteins, thymosin ß4, ubiquitin, acyl-coA binding protein, cystatin A, S100A11, cytochrome c and macrophage migration inhibitory factor. The identity of these proteins was validated by immunohistochemistry, Western blotting and MALDI imaging mass spectrometry (IMS). MALDI IMS localized the candidate biomarker proteins specifically to high grade preinvasive lesions and invasive tumors. This novel proteomic signature may facilitate the selection and monitoring of high risk individuals for lung cancer early detection and chemoprevention strategies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2727.

DNA- versus RNA-based methods for human papillomavirus detection in cervical neoplasia

Objective. To compare DNA-based and mRNA-based methods for detection of high-grade cervical neoplasia in Norway. Methods. HPV prevalence was analyzed in 383 women with positive index cytology, selected from gynecology clinics. All patients were investigated by a new PAP smear, histology, and two commercially available HPV tests: Hybrid Capture II (Digene, Gaithersburg, MD) and the Pre Tect HPV-Proofer (NorChip AS). Cases with positive DNA test and negative mRNA test and cases with high-grade histology and negative HPV tests were retested with PCR and sequencing. We regarded the infection as latent or transient if sequencing revealed an HPV type included in both assays. Results. High-risk HPV was detected in 99.7% of the histological confirmed high-grade lesions (CIN2+) (290/291). The DNA test was positive in 95% (275/291), and the mRNA test was positive in 77% (225/291) of the histological confirmed high-grade lesions. All invasive carcinomas were mRNA positive. The DNA test was significantly more often positive in benign and low-grade lesions, some of which were found to be false positive due to cross-contamination with unrelated types. High-grade histology was detected in 83% of women with normal cytology and positive mRNA test. Latent or transient infections were detected in 11 low-grade and 12 high-grade preinvasive lesions. Sequencing revealed high-risk HPV types included only in the DNA test in 35 high-grade preinvasive lesions, HPV 52 and 58 were the most prevalent HPV types. Conclusions. These HPV tests have the potential to improve the detection rate of high-grade cervical neoplasia, with some limitations. The mRNA test seems to be more appropriate for risk-evaluation. Larger scale, population based studies are necessary to evaluate the predictive values of HPV testing in Norway.

Telomere Shortening and Telomerase Reverse Transcriptase Expression in Preinvasive Bronchial Lesions

Telomerase, a ribonucleoprotein complex whose activity is related to the expression of its catalytic subunit human telomerase reverse transcriptase (hTERT), restores telomere length in tumor cells and enables immortality after p53/Rb inactivation has been achieved. To determine the timing of hTERT derepression during bronchial carcinogenesis and its relationship with telomere shortening and the p53/Rb pathway alterations, we did an immunohistochemical and in situ hybridization study in preinvasive and invasive bronchial lesions. hTERT, P53, P16, cyclin D1, Bax-to-Bcl2 ratio, and Ki67 immunostainings were done in 106 preneoplastic lesions and in paired lung carcinoma and normal bronchial mucosae. Concomitantly, hTERT mRNA levels and qualitative telomere shortening were assessed by in situ hybridization and fluorescence in situ hybridization, respectively, in a subset of preneoplastic and neoplastic lesions. Telomerase was increasingly expressed from normal epithelium to squamous metaplasia, dysplasia, and carcinoma in situ, and decreased in invasive carcinoma (P < 0.0001), with a direct correlation between protein and mRNA levels of expression (P < 0.0001). hTERT expression was directly correlated with P53, Ki67, and Bcl2-to-Bax ratio, suggesting a coupling between telomerase reactivation, proliferation, and resistance to apoptosis. Telomere signals significantly decreased as early as squamous metaplasia and progressively increased over the spectrum of preneoplastic lesions. Telomere shortening represents an early genetic abnormality in bronchial carcinogenesis, preceding telomerase expression and p53/Rb inactivation, which predominate in high-grade preinvasive lesions.

Synchronous lesions detected by autofluorescence bronchoscopy in patients with high-grade preinvasive lesions and occult invasive squamous cell carcinoma of the proximal airways

The cancerisation field concept implies that lung cancer multicentricity may be a frequent event and primary studies using white-light bronchoscopy (WLB) have reported a high prevalence of multicentricity in patients with roentgenographically occult lung cancer. We have used autofluorescence bronchoscopy (AFB) to reassess the prevalence of synchronous lesions in patients referred for the staging and/or treatment of occult lesions initially detected during WLB. All the patients referred with high-grade preinvasive lesions (severe dysplasia, DYS S and carcinoma in situ, CIS) and occult invasive squamous cell carcinoma (CIV) of the bronchus initially detected during WLB at other centers, underwent AFB. Data were prospectively collected and retrospectively analyzed to assess the prevalence of synchronous occult lesions. From January 1996 to December 2001, 28 patients (26 males, 2 females; mean age: 65 ± 11) were assessed. After re-evaluation, in two cases, the referred lesions corresponded only to metaplasia and were discarded from analysis. The 26 other patients were referred for 28 lesions (3 DYS S, 19 CIS and 6 CIV; 2 patients were referred with two synchronous lesions). AFB revealed, in these 26 patients, six additional lesions (1 DYS S, 4 CIS and 1 CIV). Multicentricity in this group, initially estimated to amount to 7% with WLB alone, raised to 23% by using AFB. The high prevalence of synchronous lesions in this series of patients with occult DYS S, CIS and occult CIV suggests that AFB may be a useful adjunct in the pretreatment evaluation.

Clinical prognostic indicators of high-grade pre-invasive bronchial lesions

Lung cancer arises from multistep genetic damage of bronchial epithelium, driving multifocal progressive dysplastic lesions. However, the risk of progression of high-grade pre-invasive bronchial lesions to cancer is poorly assessed. The purpose of this study was to better define the parameters that predict the outcome of these lesions. The current authors prospectively studied 27 patients with 31 histologically proven severe dysplasia (SD) and carcinoma in situ (CIS), with repeated bronchoscopy and endobronchial treatment. The influence of respiratory-cancer history, histopathological classification, tobacco consumption, and number of biopsies on the progression rate into cancer was studied. The actuarial progression rate to cancer was 17% at 1 yr and 63% at 3 yrs. A total of 11 cases of CIS progressed to invasive cancer, 17 were stable or regressed during the study, two with SD regressed and one progressed to invasive cancer. Progression of CIS appeared more frequent in lesions diagnosed as "questionable CIS". Persistence of smoking did not influence high-grade lesion outcome. The existence of synchronous lung cancer did not seem to impact on progression. The number of biopsies did not influence the outcome. In conclusion, the current study suggests that the outcome of high-grade pre-invasive lesions is not modified by the number of biopsies performed on these lesions. Careful pathological examination of these lesions and pathological revision seem necessary, since questionable cases have the worse progression rate.

Optimization of biotinyl-tyramide-based in situ hybridization for sensitive background-free applications on formalin-fixed, paraffin-embedded tissue specimens.

BackgroundOver the past five years in situ hybridization techniques employing tyramide amplification reagents have been developed and promise the potential detection of low/single-copy nucleic acid sequences. However the increased sensitivity that tyramide amplification brings about may also lead to problems of background staining that confound data interpretation.MethodsIn this study those factors enabling background-free biotinyl-tyramide based in situ hybridization assay of formalin-fixed paraffin-embedded tissues have been examined. SiHa, HeLa and CaSki cell lines known to contain HPV integrated into the cell genome, and archival cervical pre-invasive lesions and carcinomas have been successfully assessed using biotinylated HPV and centromeric probes.ResultsThe single most important factor both for sensitivity and clean background was a tissue unmasking regimen that included treatment with 10 mM sodium citrate pH 6.0 at 95°C followed by digestion with pepsin/0.2 M HCl. Concentrations both of probe and primary streptavidin-peroxidase conjugate and pH of hybridization mix and stringency washes were also critical for sensitivity. Certain probes were more associated with background staining than others. This problem was not related to probe purity or size. In these instances composition of hybridization mix solution was especially critical to avoid background. 3-amino-9-ethylcarbazole was preferred over 3,3'-diaminobenzidene as a chromogen because background was cleaner and the 1–2 copies of HPV16 integrated in SiHa cells were readily demonstrable. HPV detection on metaphase spreads prepared from SiHa cells was only successful when a fluorescent detection method was combined with tyramide reagent. 'Punctate' and 'diffuse' signal patterns were identified amongst tissues consistent with the former representing integration and 'diffuse' representing episomal HPV. Only punctate signals were detected amongst the cell lines and were common amongst high-grade pre-invasive lesions and carcinomas. However it remains to be determined why single/low-copy episomal HPV in basal/parabasal cells of low-grade lesions is not also detectable using tyramide-based techniques and whether every punctate signal represents integration.ConclusionsA tyramide-based in situ hybridization methodology has been established that enables sensitive, background-free assay of clinical specimens. As punctate signals characterize HPV in high-grade cervical lesions the method may have potential for clinical applications.

Cigarette Smoking, Preinvasive Bronchial Lesions, and Autofluorescence Bronchoscopy

Autofluorescence bronchoscopy (AFB), when used as an adjunct to standard white light bronchoscopy (WLB), enhances the bronchoscopist's ability to localize small neoplastic lesions, especially intraepithelial lesions. The current study was undertaken in order to define the population in which the rate of detection is higher using AFB. Two hundred forty-four consecutive patients, who were symptomatic smokers or patients who previously had been treated for lung cancer or head and neck cancers, underwent WLB and AFB. All patients with endoscopic abnormalities underwent biopsies. Data concerning smoking history were prospectively registered. We report the prevalence of high-grade or invasive lesions at the time of examination. On a lesion-by-lesion analysis, 92 low-grade lesions, 42 high-grade lesions (ie, moderate dysplasia, severe dysplasia, and carcinoma in situ), and 39 invasive carcinomas were diagnosed. There was no effect of age, gender, and age at smoking initiation on the prevalence of preinvasive or invasive lesions. The 10 patients who previously had undergone surgery for lung cancer and exhibited high-grade preinvasive lesions had a history of carcinoma of the epidermoid histologic type (p = 0.01). These 10 patients displayed multiple lesions in the bronchial tree (mean No. of lesions, 1.8 per patient). In current smokers, the prevalence of high-grade or invasive lesions were both related to the number of pack-years smoking had occurred (p = 0.01) and to the duration of smoking (p = 0.01). In contrast, the prevalence of preinvasive lesions in former smokers was related to a history of epidermoid carcinoma. AFB should be recommended in patients with a history of epidermoid carcinomas of the lung. Current smokers with a prolonged smoking history appear to comprise a population in which the rate of detection of preneoplastic lesions is high with AFB.

Loss of heterozygosity: a potential tool in management of oral premalignant lesions?

Oral leukoplakia, a heterogeneous group of lesions, demonstrates a varying degree of risk for cancer progression. Histology (presence and degree of dysplasia), the current gold standard for assessing this risk, is reasonably effective in judging the malignant risk of high-grade pre-invasive lesions. It is, however, a poor predictor for lesions without dysplasia, or with minimal dysplasia, as only a few of these lesions will progress to cancer. This poses an enormous dilemma for clinicians as to whether these lesions should be aggressively treated or not. Recent studies show that loss of specific chromosomal regions (loss of heterozygosity, LOH) that contain known or presumptive tumor suppressor genes is an early predictor of subsequent progression of oral premalignant lesions. Incorporation of LOH findings into staging of oral premalignancy could improve our ability to identify and manage high-risk premalignant lesions, particularly those with relatively benign histology but high-risk genetic changes (high-risk LOH pattern).

Sex-related differences in bronchial epithelial changes associated with tobacco smoking.

Lung cancer is the most common cause of cancer death in North American women. Because smoking-related changes in the bronchial epithelium and in lung function have not been studied in detail in women, we used fluorescence bronchoscopy-directed biopsy to determine the prevalence of high-grade preinvasive lesions in former and current smokers of both sexes. Spirometry, white-light bronchoscopy, and fluorescence bronchoscopy were performed in 189 women and 212 men older than 40 years of age who had smoked 20 pack-years or more (pack-years = number of packs of cigarettes smoked per day x number of years of smoking). Carcinoma in situ was found in 1.8% of the subjects, severe dysplasia was found in 6.5%, and moderate dysplasia was found in 14% (all preinvasive lesions). Compared with men, women had a lower prevalence of high-grade preinvasive lesions in the observed airways (14% versus 31%; odds ratio = 0.18; 95% confidence interval = 0.04-0.88), and women with preinvasive lesions had fewer such lesions (two-sided P = .048). The prevalence of preinvasive lesions did not change substantially for more than 10 years after cessation of smoking. Lung function was associated with the prevalence of preinvasive lesions, but the association was weaker in women than in men. If the presence of airflow obstruction was defined by an FEV1/FVC (forced expiratory volume in 1 second/forced vital capacity) value of 70% or less, only 56% of the men and 44% of the women with preinvasive lesions had abnormal lung function. In developing strategies for chemoprevention or early detection of lung cancer in high-risk populations, it is important to consider the effect of sex and arbitrarily chosen lung function values on the prevalence of preinvasive airway lesions.