Cases Of Squamous Intraepithelial Lesion Research Articles

Paraffin section thickness in immunohistochemical detection of p16 expression in cervical tissue samples

To investigate paraffin section thickness in immunohistochemical detection of p16 expression in cervical tissue samples. p16 immunohistochemical staining was performed in 150 cases of chronic cervicitis, 126 cases of low-grade squamous intraepithelial lesions(LSIL), 96 cases of high-grade squamous intraepithelial lesions (HSIL) and 78 cases of cervical cancer from January 2014 to March 2018 in Zhongshan Boai Hospital. The results of p16 protein expression in paraffin sections with thickness of 2, 3, 4, 5 and 6 μm were compared using Logistic regression analysis. With the increase of slice thickness, the staining of p16 protein in nucleus gradually increased. The thickness of cervical slices in chronic cervicitis and cervical cancer samples had no significant effect on the positive rate of p16 protein(χ2=7.817 and 1.332, both P>0.05), while the thickness of slices in LSIL and HSIL samples had significant effect on the positive rate of p16 protein (χ2=17.688 and 10.182, P<0.05 or P<0.01). The stable and reliable results were obtained when the slices were between 3 and 5 μm thick. Paraffin sections with thickness of 3.0-5.0 μm are recommended for immnohistochemical staining of p16 protein in cervical tissue samples.

Human papilloma virus infection in HIV-infected women in Belgium: implications for prophylactic vaccines within this subpopulation.

Although high-risk (HR) human papilloma virus (HPV) infection is the primary causative factor for cervical squamous intraepithelial lesions and invasive cervical cancer, the epidemiology of potentially HR (pHR) and low-risk HPV still remains to be elucidated in HIV-infected women. In addition, the synergistic potential of the multiplicity of HPV infections harboured renders it difficult to model the impact of vaccines. This cross-sectional analysis of HIV-infected women explores the epidemiology of abnormal cytology, thereby profiling and pairing pHR/HR HPV genotypes. This cross-sectional analysis reports the findings of 593 HIV-infected women, who underwent a cytological examination and HPV genotyping. A logistic regression model was fitted to adjust for age and coinfection with pHR/HR HPV genotypes. In the 143 women with abnormal cytology, a multiple pHR/HR HPV genotype prevalence of 64.1% [95% confidence interval (CI): 44.6-57.6%] was observed. A combined prevalence of HPV 16 and HPV 18 of 29.6% (95% CI: 22.2-37.8%) was found. HPV 6 and HPV 66 were found in two cases of low-grade squamous intraepithelial lesions as stand-alone genotypes and HPV 53 in a high-grade squamous intraepithelial lesion case. Pairing involving HPV 31 with HPV 16 and HPV 58 was found in high-grade squamous intraepithelial lesion cases. Significant associations were observed between abnormal cytology, multiple HPV, HPV 39 and HPV 53 [adjusted odds ratio (aOR): 2.02; P=0.01; 95% CI: 1.2-3.5; aOR: 3.8; P=0.01; 95% CI: 1.4-10.7; and aOR: 0.5; P=0.03; 95% CI: 0.2-0.9, respectively]. Coinfection with pHR/HR HPV genotypes HPV 39 and 53 was significantly associated with abnormal cytology. Research into the imputed role of HPV 31 in pairings, low-risk and pHR HPV genotypes in HIV-infected women is warranted.

Risk of high-grade lesions after atypical glandular cells in cervical screening: a population-based cohort study

ObjectivesTo determine how human papillomavirus (HPV) positivity of atypical glandular cells (AGCs) affects the predictive values for the presence of high-grade cervical lesions.DesignPopulation-based cohort study.SettingStockholm-Gotland region, Sweden.ParticipantsBetween 17 February 2014...

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

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

Expressions of peroxisome proliferator-activated receptor γ, retinoic acid X receptor α and cyclooxygenase 2 in cervical squamous cell carcinoma and their significances

Objective To study the functions of peroxisome proliferator-activated receptor γ (PPARγ), retinoic acid X receptor α (RXRα) and cyclooxygenase 2 (COX-2) in the carcinogenesis of cervical squamous cell carcinoma (SCC). Methods The expressions of PPARγ, RXRα and COX-2 in 17 cases of normal cervical epithelium (NCE), 72 cases of squamous intraepithelial lesion (SIL) and 42 cases of cervical SCC were detected with immunohistochemical method respectively. Results The positive expression rates of PPARγ in the NCE, SIL and cervical SCC group were 23.5% (4/17), 58.3% (42/72) and 83.3% (35/42)respectively; the positive expression rates of RXRα in the NCE, SIL and cervical SCC group were 29.4% (5/17), 54.2% (39/72) and 90.5% (38/42) respectively. No significant expression of COX-2 was found in the NCE, while the positive expression rates of COX-2 in SIL and cervical SCC were 36.1% (26/72) and 57.1% (24/42) respectively. The positive expression rates of PPARγ, RXRα and COX-2 in high-grade SIL group were higher than those in low-grade SIL group (all P < 0.05). In cervical SCC group, the positive expression rate of COX-2 with lymph node metastasis was higher than that without lymph node metastasis (χ2= 3.98, P= 0.04). Conclusion PPARγ, RXRα and COX-2 might be all involved in the carcinogenesis of SCC. Key words: Uterine cervical neoplasms; Carcinoma, squamous cell; Squamous intraepithelial lesion; Peroxisome proliferator-activated receptor γ; Retinoic acid X receptor α; Cyclooxygenase 2

Human papillomavirus (HPV) E6/E7 mRNA detection in cervical exfoliated cells: a potential triage for HPV-positive women

Cytology triage has been generally recommended for human papillomavirus (HPV)-positive women, but is highly dependent on well-trained cytologists. The present study was designed to explore whether HPV E6/E7 mRNA detection in cervical exfoliated cells can be a potential triage for HPV-positive women from a clinic-based population. Both the primary HPV testing and Papanicolaou (Pap) test were performed on all eligible HPV-positive women. HPV E6/E7 mRNA was detected by QuantiVirus® HPV E6/E7 mRNA assay in cervical exfoliated cells. All HPV-positive women underwent colposcopy and further biopsy if indicated. The data were assessed by Pearson's Chi-squared test and the receiver operating characteristic curve. A total of 404 eligible HPV-positive women were enrolled. Positive rate of E6/E7 mRNA in high-grade squamous intraepithelial lesion (HSIL) cases was higher than that in low-grade squamous intraepithelial lesion (LSIL) or normal cases. There was no statistical difference found between mRNA and cytological testing with sensitivity (89.52% vs. 86.67%, P=0.671), specificity (48.96% vs. 48.96%, P=1.000), positive predictive value (39.00% vs. 38.24%, P=1.000), and negative predictive value (92.76% vs. 90.97%, P=0.678) for detecting ≥HSIL. HPV E6/E7 mRNA detection in cervical exfoliated cells shows the same performance as Pap triage for HSIL identification for HPV-positive women. Detection of HPV E6/E7 mRNA may be used as a new triage option for HPV-positive women.

Study of cytodiagnosis of discharge per vaginum with specific reference to human papilloma virus and herpes simplex virus at tertiary care center, Indore

Background: Cervical cancers are the second most frequent type of female cancer. Human papillomavirus (HPV) infection is the most important risk factor for cervical cancer. Objective: The aim is to detect cytomorphological changes of HPV and herpes simplex virus (HSV) to early diagnose cervical cancer to prevent it at early stage. Materials and Methods: The study includes total 1542 patients presenting with the complaints of vaginal discharge and/or associated symptoms. Samples were taken, and prepared smear was stained with papanicolaou (PAP) stain and reporting was done according to The Bethesda system - 2014. The study was prospective study and statically analyzed. Results: Totally, 1542 PAP smears were analyzed. Out of which, normal smears 364 (23.61%), inadequate smears 58 (3.76%), inflammatory smear 1093 cases (70.88%), and epithelial cell abnormality comprises 27 cases (1.75%). Out of 27 cases, atypical squamous cells of undetermined significance was the most common epithelial cell abnormality (63%). Cytomorphological features of HPV infection are seen in 2 cases of low-grade squamous intraepithelial lesion, 2 cases of high-grade squamous intraepithelial lesion, and 5 cases of the malignant lesion while inflammatory smear suspicious of HSV comprises 2 cases (0.13%). Conclusions: The incidence of cervical cancer can be decreased if PAP smear screening is done at an early age and in the females having high-risk factors.

Cervical cytopathological changes among women with vaginal discharge attending teaching hospital.

Aims:To find cytology changes among women attending obstetrics and gynaecology clinic with complaints of vaginal discharges.Settings and Design:This descriptive hospital-based cytological study was conducted at the outpatient clinic of the obstetrics and gynaecology department.Materials and Methods:Two hundred women with complaints of vaginal discharge were selected. Their detailed histories were documented on a special request form. Pap smears were then obtained and sent for cytological examination to the cytopathology department. All low-grade squamous intraepithelial lesion (LSIL) cases were advised to follow-up with Pap smears in the next 6–12 months. Those with high-grade squamous intraepithelial lesion (HSIL) were further investigated by a cervical biopsy and managed accordingly.Statistical Analysis Used:The statistical analysis was performed using, the Statistical Package for Social Science (SPSS). Chi-square and cross-tabulation were used in this study.Results:The cytological examination of Pap smears showed no changes (i.e. negative findings) in 88 (44%) cases, while Candida species infection was the most prevalent, which was found in 67 (33.5%) of the cases. Bacterial vaginosis was found in 39 women (19.5%); 6 women (3%) were reported with dyskaryotic changes. Two cases were found to have LSIL and 4 women had HSIL.Conclusion:Infection is common among the illiterate group of women. Women with vaginal discharges should undergo screening tests for evaluation by cervical smear for the early detection of cervical precancer conditions. There is an urgent need to establish a screening program for cervical cancer in Sudan.

Rare subtype(s) and frequency of multi-viral subtype high-risk human papilloma virus infection in high-grade squamous intraepithelial lesion and squamous cell carcinoma in a cervical carcinoma prevalent developing country: a multiplex real-time polymerase chain reaction-based pilot study.

BackgroundBangladesh, with a population of 160 million and nearly half being women, has the 4th highest rate of cervical carcinoma deaths in the world. It is projected that ∼500,000 of these women would die of this entirely preventable cancer by 2030. HPV vaccination is not widely offered in Bangladesh. This pilot study is designed to find out the prevalence of rare and multi-viral high-risk HPV (hrHPV) subtype(s) infection which may help strategize a large scale vaccination program in tackling cervical carcinoma in the country.MethodsForty cases of cervical High-Grade squamous intraepithelial lesion (HSIL) and Squamous cell carcinoma (SqCa) were collected. DNA was extracted from tissue representing HSIL and SqCa and multiplex PCR was run to identify all 15 hrHPV subtypes along with known positive controls.ResultsOf the total, 27 cases were biopsies/cones and 13 were hysterectomies including 5 HSIL and 35 SqCa. Infection caused by rare subtypes, hrHPV 45 and 52, were found in only two cases. Multi-subtype infection, detected in 28 % cases, was limited to HPV16/18 in all cases but one; one case showed hrHPV16/52 combination.ConclusionA remarkable homogeneity of hrHPV 16 infection is noted in women with HSIL & SqCa in this country in these limited samples. This finding is in sharp contrast to the reports from western countries of frequent multi-viral and rare subtype hrHPV infection. This pilot study suggests that a vaccination program may be highly effective in controlling cervical cancer there. A larger study, however, is required to ratify the findings.

High-grade squamous intraepithelial lesion arising adjacent to vulvar lymphangioma circumscriptum: a tertiary institutional experience.

Lymphangioma circumscriptum of the vulva occurs in patients who have undergone radical hysterectomy, lymph node dissection, or radiation therapy for management of advanced uterine cancer. Since vulvar lymphangioma circumscriptum typically presents as multiple, grossly verrucous vesicles of various sizes, it may be impossible to clinically distinguish vulvar lymphangioma circumscriptum from other vulvoperineal cutaneous diseases. In the present study, 16 (1.6%) out of the 1,024 vulvar biopsy or excision specimens were diagnosed as lymphangioma circumscriptum. In two (12.5%) out of the 16 cases, unusual histopathological findings were observed. Both patients had previously undergone radical hysterectomy with lymph node dissection and postoperative radiation therapy or concurrent chemoradiation therapy for advanced cervical cancer. Microscopic examination revealed high-grade squamous intraepithelial lesions, which were located immediately adjacent to the normal squamous epithelium covering the dilated subepithelial lymphatic vessels. Further, human papillomavirus genotyping confirmed that both patients were infected with high-risk human papillomavirus. High-grade squamous intraepithelial lesion cannot be grossly distinguished from vulvar lymphangioma circumscriptum because the multiple, verrucous vesicles that constitute the characteristic gross appearance of vulvar lymphangioma circumscriptum hinder its distinction. In this regard, our cases of high-grade squamous intraepithelial lesion, located adjacent to vulvar lymphangioma circumscriptum, support the notion that active surgical excision is necessary for the treatment of vulvar lymphangioma circumscriptum.

Association between folate status and cervical intraepithelial neoplasia.

Background/Objectives:To investigate the effect of folate status on cervical intraepithelial neoplasia (CIN) progression and its relationship with high-risk human papillomavirus (hrHPV).Subjects/Methods:We evaluated 20 000 sexually active women aged <65 years in Yangqu County by using a questionnaire; the subjects were also screened using the ThinPrep cytologic test (TCT). Patients with abnormal TCT results (other than glandular cell abnormalities) who were willing to provide informed consent were further diagnosed using colposcopy and histopathological examination. We investigated 247 cases of low-grade cervical squamous intraepithelial lesions (LSIL), 125 cases of high-grade cervical squamous intraepithelial lesions (HSIL) and 877 controls. A 24-item food frequency questionnaire was filled out by the investigator to estimate the consumption of dietary folate. Positivity for hrHPV from residual exfoliated cervical cells was tested; serum folate was also measured.Results:The hrHPV infection rate in HSIL patients (77.6%) was higher than that in LSIL (33.2%) and control (32.0%) patients. Dietary folate intakes in controls, LSIL and HSIL were 306.9±176.6, 321.8±168.0 and 314.7±193.8 μg/kcal, respectively. The levels of serum folate in controls, LSIL and HSIL were 18.2±7.9, 15.9±7.1 and 14.3±7.5 nmol/l, respectively. Increased CIN correlated with higher rates of hrHPV infection and lower levels of serum folate.Conclusions:Low levels of serum folate may increase the risk of CIN progression. Furthermore, potential synergy may exist between low serum folate levels and hrHPV infection to promote CIN development.

The performance of tele-cervicography for detection of preinvasive and invasive disease of the uterine cervix as an adjunctive test to Pap smears.

Aim of the studyTo evaluate the diagnostic capacity of tele-cervicography for the detection of cervical neoplasia as an adjunctive test with Papanicolaou (Pap) smears.Material and methodsPap smear and tele-cervicography were performed on each subject. Histologic results were obtained for all patients.ResultsOf the 863 females who had a tele-cervigram, 252 (29.2%) had a positive result. Of the 60 histologically confirmed cases of high-grade squamous intraepithelial lesions (HSILs), 56 (93.3%) were detected by tele-cervicography, including 16 (26.7%) with a positive grade of 1 and 40 (66.7%) with a positive grade of 2. With the positive threshold of tele-cervicography set as any positive grade (P0 to P3), the overall sensitivity was 94.0% (95% CI: 88.0–97.3%), the specificity was 80.9% (95% CI: 80.0–81.5%), and the positive likelihood ratio was 4.94 (95% CI: 4.23–5.77) for the detection of HSILs or cancer. The combination of tele-cervicography with Pap smear testing for the detection of HSILs or cancer resulted in an increase in sensitivity from 84.6% (Pap only: cutoff = atypical squamous cells of undetermined significance or more severe) to 98.3% (Pap plus tele-cervicography: cutoff = P0 or more severe).ConclusionsThe sensitivity of tele-cervicography was higher than that of cytology for the detection of cervical neoplasia, and combining the two tests increased the sensitivity. Tele-cervicography can be considered a useful complementary tool to cytology.

Prevalence of Anal Dysplasia in Patients With Inflammatory Bowel Disease

Although the prevalence of anal dysplasia is higher in some immunosuppressed populations, the prevalence in patients with inflammatory bowel disease (IBD) is unknown. We examined the prevalence of abnormal anal cytology among IBD patients, and its relation to the human papilloma virus (HPV). Adults with IBD and age-matched healthy controls (HC) were recruited. IBD patients were categorized as nonimmunosuppressed (IBD-N) or immunosuppressed (IBD-I). Anal Papanicolaou tests were performed for HPV testing and classification by a cytopathologist as follows: negative, atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion, cancer, or unsatisfactory. A total of 270 subjects (100 IBD-I, 94 IBD-N, and 76 HC) were recruited. ASC-US were detected in 19 subjects, with a trend toward a higher prevalence among IBD subjects compared with HC (8.8% vs 2.6%; P = .10). The prevalence did not differ with respect to immunosuppression. Crohn's disease (CD) subjects had a higher prevalence of ASC-US compared with others with IBD (P = .02). Among those with CD, female sex and disease duration longer than 10 years were risk factors. There were no cases of low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion, or anal cancer in the cohort. HPV was present in 5.3% and 1.5% of subjects with and without ASC-US, respectively (P = .26). Although there was a trend toward abnormal anal Papanicolaou tests in IBD subjects compared with HC, there was no difference based on immunosuppression. The presence of HPV did not correlate with abnormal anal cytology. Risk factors associated with this increased trend include female CD subjects and those with a longer duration of CD. ClinicalTrials.gov number: NCT01860963; https://clinicaltrials.gov/ct2/show/NCT01860963.

Squamous intraepithelial lesions and squamous cell carcinomas detected by endometrial sampling: Pap test correlation and outcome data

Squamous intraepithelial lesions (SIL) and squamous cell carcinomas (SCC) can rarely be detected in endometrial sampling. We reviewed all cases of SIL and SCC detected solely on endometrial biopsies and curettings to determine their significance and whether these findings were detected on prior or concurrent Papanicolaou (Pap) test. Endometrial samples with detached fragments of SIL and SCC over a 13-year period were reviewed, along with prior and/or concurrent Pap tests, human papillomavirus status, and subsequent pathology results. Cases with concurrent cervical or endocervical sampling that showed SIL or SCC were excluded. Fifty patients had endometrial biopsies and/or curettings with SIL or SCC. Thirty-six patients (72%) had concurrent or previous Pap tests within 1 year prior to the endometrial sampling. The Pap test was negative for intraepithelial lesion or malignancy in 44% of patients (16/36) and atypical squamous cells of undetermined significance in 22% of patients (8/36). The source of the SIL and SCC in endometrial sampling was cervical SIL in 18 patients, cervical SCC in 14 patients, endometrioid carcinomas in 3 patients, metastatic carcinoma in 1 patient, and not definitively identified in 14 patients. The majority of SIL and SCC in endometrial samples are from the cervix. Prior and concurrent Pap tests were often negative for intraepithelial lesion or malignancy in patients with SIL and SCC detected by endometrial samples. This suggests that SIL and SCC detected on endometrial sampling may detect a subset of cervical SIL/SCC that are more proximal in the endocervical canal and are not sampled with conventional Pap tests.

Abstract 5368: Genetic susceptibility to cervical cancer: Role of XRCC1

Abstract Background: X-ray repair cross-complementation group 1 (XRCC1) is a scaffold protein involved in the early and late stages of Base Excision Repair (BER). Three single nucleotide polymorphisms occur in XRCC1, resulting in non-synonymous amino acid changes, which could change the binding or regulatory activities of XRCC1. Human papillomavirus (HPV) is considered to be a necessary but not sufficient cause for cervical cancer and, therefore, other factors contribute to the carcinogenic process. A hereditary component for this neoplasia has been reported and several studies indicate that genetic background of the host is important for cervical cancer susceptibility. Previous studies investigating the association of (XRCC1) polymorphisms with squamous intraepithelial lesions (SIL) and cervical cancer (CC) risk has provided inconsistent results. The aim of our study was to assess the association between the XRCC1 gene Arg194Trp, Arg399Gln, Arg280His polymorphisms as well as its expression and risk of SIL and CC. Methods: A case control study consisting of 178 samples (65 CC cases, 45 SIL cases and 68 controls) was carried out. HPV DNA detection was performed by consensus PCR and genotyping of positive samples by type specific primers. XRCC1 polymorphisms were determined by Restriction Fragment Length Polymorphism (RFLP). Expression at mRNA level was checked by Real Time PCR and at protein level by Western blotting. Results: The SNPs in XRCC1 gene was associated with increased risk of SIL and CC. The TT genotype of XRCC1 codon 194 and AA genotype of XRCC1 codon 280 presented 12 fold (p=0.001; OR=12.2; 95%CI=4.9-30.9) and 7.5 fold (p=0.001; OR=7.5; 95%CI=2.9-18.7) higher risk of cervical cancer, respectively. The variant genotype of XRCC1 codon 399 was associated with 4.2 fold (p=0.008; OR=4.2; 95%CI=1.5-12.1) higher risk of cervical cancer. The heterozygous genotype of all the three exons did not present any significant risk. In XRCC1 C194T, and XRCC1 G280A combining the heterozygous and variant genotype there was higher risk for CC (p=0.001; OR=7.01 95%CI=3.1-15.7 and p=0.001, OR=3.2, 95%CI=1.6-6.6, respectively). In SIL cases, the homozygous variant TT of Exon 6 presented 3.5 fold (p=0.012; OR=3.5; 95%CI=1.3-9.8) higher risk. The combined variant genotype (CT+TT) also showed an elevated risk of SIL (p=0.003, OR=3.3). The invasive cancer and SIL subjects demonstrated lower relative expression of the XRCC1 (p&amp;lt;0.001). Reduction was also found on the protein level. Conclusions: The present study suggested that XRCC1 as a predisposing factor in cervical precancer and increased risk of invasive cervical cancer. Low mRNA transcript of XRCC1 showed an increased risk of cervical cancer irrespective of HPV status, as majority of cervical cancer and SIL samples were HPV positive. This implies that polymorphism and reduction in expression of XRCC1 gene is associated with an early event in the progression to cervical cancer. Note: This abstract was not presented at the meeting. Citation Format: Deepti Bajpai, Ayan Banerjee, Sujata Pathak, Sunesh Jain, Neeta Singh. Genetic susceptibility to cervical cancer: Role of XRCC1. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5368. doi:10.1158/1538-7445.AM2014-5368

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.

Cytokine profile in cervical mucosa of Japanese patients with cervical intraepithelial neoplasia

Immune responses in the uterine cervix are considered to play an important role in persistent human papillomavirus (HPV) infection and carcinogenesis, but many aspects of the mechanism are still unclear. The goal of this study was to measure cytokines to analyze immune responses in patients with cervical intraepithelial neoplasia (CIN). The levels of 17 cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, G-CSF, GM-CSF, INF-γ, MCP-1, MIP-1β, and TNFα) in cervical mucus were simultaneously measured using a multiplex immunoassay in 52 high-grade squamous intraepithelial lesion (HSIL) cases and overproduction of IL-1β, IL-8, and MIP-1β was identified. The levels of these 3 cytokines were measured in 130 patients with or without CIN lesions using enzyme-linked immunosorbent assay. The associations of the cytokine levels with the cytology, infecting HPV type, and status of cigarette smoking were investigated. IL-1β and IL-8 levels were associated with the cytology, and these levels were higher in HSIL cases than in NILM (negative for intraepithelial lesion and malignancy) and LSIL (low-grade squamous intraepithelial lesion) cases (P = 0.005, P = 0.001, respectively). The MIP-1β level was significantly lower in smokers (P = 0.018) and high-risk (HR)-HPV-infected patients (P = 0.021). Enhanced expression of IL-1β and IL-8 indicates that Th2 inflammatory responses become stronger in the local uterine cervical region with the progression of CIN lesions, and a decrease in the MIP-1β level may be advantageous for immunoescape of HPV. Cigarette smoking may further facilitate persistent HPV infection.

A selection of monitoring parameters for gynecologic cytology—Beacons of light for quality assurance

A selection of monitoring parameters for gynecologic cytology—Beacons of light for quality assurance

Diagnostic and prognostic significance of image cytometric DNA ploidy measurement in cytological samples of cervical squamous intraepithelial lesions

To study the DNA ploidy pattern of uterine cervical squamous intraepithelial lesions (SILs) and its diagnostic and prognostic significance. The study included 31 cases of SIL: 11 low-grade (LSIL) and 20 high-grade (HSIL). Feulgen-pararosaniline staining was performed on previously Papanicolaou-stained smears and a DNA image cytometric study was performed. An internal reference was used to calibrate the samples. All 31 cases of SIL, either LSIL or HSIL, were non-diploid. Of the 11 cases of LSIL, four were tetraploid and seven were aneuploid, whereas, of the 20 cases of HSIL, four were tetraploid and 16 were aneuploid. Stemline aneuploidy was not a significant discriminator between LSIL and HSIL (P=0.32). Based on single-cell analysis, HSIL cases had significantly higher DNA content than LSIL cases (P<0.01). When a mean of 30% or more was used for the 6c-exceeding event (6cEE) value, the sensitivity and specificity to indicate HSIL were 83% and 64%, respectively, with a positive predictive value (PPV) of 81% and negative predictive value (NPV) of 65%. All HSIL cases were cervical intraepithelial neoplasia grade 2 or worse (CIN2+) on biopsy. In addition, cases which showed recurrence had more DNA content by single-cell analysis than those with an indolent clinical behaviour: P=0.04 and P=0.03 for LSIL and HSIL, respectively. Image cytometric DNA analysis is a useful technique for diagnostic and prognostic purposes in uterine cervical SIL when appropriate 'c' values are used in single-cell analysis. We propose that a >6c DNA content of 30% is useful as a cut-off level for predicting cases with CIN2+ in DNA image cytometry of cervical smears.

High-Risk Human Papillomavirus Detection in Women With Low-Grade Squamous Intraepithelial Lesions or Higher-Grade Cytology Using the Cervista HPV HR Test

High-risk human papillomavirus (HR-HPV) persistence is thought to be necessary for the development of cervical cancer. Because not all cases of low-grade squamous intraepithelial lesion (LSIL) or higher-grade squamous intraepithelial lesion are associated with HR-HPV, detection of HR-HPV in women with these cervical abnormalities may be clinically useful for management. The aim of this study was to detect HR-HPV in women with LSIL or higher-grade cytology. In a multicenter, prospective clinical study, residual liquid-based cytological specimens from 3,966 US women were analyzed. Women with LSIL or higher-grade cytology underwent colposcopy and cervical biopsy as clinically indicated. The test was used to detect HR-HPV in women with cytologically diagnosed LSIL or higher, with histological confirmation of cervical intraepithelial neoplasia 2 (CIN 2) or worse by a central review panel. Among subjects with LSIL or higher-grade cytology and complete data sets, 11.8% (41/347) were diagnosed with CIN 2 or worse; 82.1% (285/347) were HR-HPV positive. The prevalence of CIN 2 or worse and CIN 3 or worse was 14.4% (41/285) and 7.0% (20/285), respectively, among subjects who were HR-HPV positive. All subjects diagnosed with CIN 2 or worse (41/41) and CIN 3 or worse (20/20) tested positive for HR-HPV. Sensitivity and negative predictive value calculated for CIN 2 or worse were 100% (95% CI = 91.4%-100.0%) and 100% (95% CI = 94.2%-100.0%), respectively. Specificity and positive predictive value among these subjects were 20.3% (95% CI = 16.1%-25.1%) and 14.4% (95% CI = 10.8%-18.9%), respectively. Detection of HR-HPV in women with LSIL or higher-grade cytology using the HPV HR test may allow clinicians to further triage women for advanced clinical management.