Cases Of Cervical Intraepithelial Neoplasia Research Articles

Assessment of programmed death ligand 1 (PD-L1) expression in cervical intraepithelial neoplasia and carcinoma cervix

BackgroundCarcinoma cervix is a significant public health issue in low- and middle-income nations. Despite the availability of aggressive cytological screening tests and increasing accessibility of the Human Papilloma Virus vaccine, a significant proportion of patients in our country still present with locally advanced cervical cancer. The objective of this study was to estimate the prevalence of programmed death ligand 1 (PD-L1) immunoexpression in cervical intraepithelial neoplasia and carcinoma cervix and study the distribution of clinicopathological features and recurrence of cervical cancer with respect to PD-L1 status. MethodsA total of 140 patients were included in this multicentric ambidirectional study. Immunohistochemical analysis for PD-L1 was performed on paraffin-embedded, formalin-fixed sections using 22C3 PharmDx assay (Dako) and tumour proportion score was calculated. PD-L1 expression status concerning the distribution of clinicopathological features was further studied. ResultsThis study included 133 cases of cervical carcinoma and 7 cases of cervical intraepithelial neoplasia (140 cases), with a prevalence of PDL1 positivity in 31.4% of cases with 15% (n = 21) tumours high positive, 16.4% (n = 23) low positive and 68.6% (n = 96) negative for PD-L1. It was observed that all cases with PD-L1 positivity were characterized as squamous cell carcinoma. The mean age of subjects was 56.74 ± 11.52 years. PD-L1 high positivity was observed in 26.7% of individuals in the age group >70 years, 21.7% of grade 3 tumours, 11.4% of tumours exceeding 4 cm in size, and 33.3% of cases showing recurrence. PD-L1 immunoexpression did not demonstrate a significant association with the patient's age, tumour grade and stage, as well as recurrence. ConclusionIt is envisaged that anti-PD-L1 immunotherapy could show promising antitumour activity and early survival rates among patients with cervical squamous cell carcinoma.

Cervical Cancer Visual Screening Experience in the Republic of Tajikistan

OBJECTIVES: To study the results of the first pilot study of organized visual cervical cancer (CC) screening for the detection of precancerous pathology of the cervix in two pilot districts of the Republic of Tajikistan. STUDY DESIGN: In this cross-sectional study, the target group included healthy women of reproductive age (30-49 years) from Kushoniyon and B. Gafurov Districts who underwent visual screening. The total study population was 72,574 out of which 68,391 (94.3%) visited primary healthcare facilities for visual inspection with Lugol’s Iodine (VILI). A total of 2958 women with suspicious tests for cervical intraepithelial neoplasia (CIN) were identified (4.3%) and sent to the reproductive health care centers for further diagnostics. Post-screening diagnostic tests were performed to specify cervical lesions, which included colposcopy with acetic acid (VIA) visual inspection, cytology, and biopsy with histological examination. HPV testing wasn’t included in the diagnostic protocol due to its high cost. RESULTS: A total of 164 histologically confirmed cases of CIN were identified (0.25% of number of women screened). The detection rate of precancerous pathology was 26.9 per 100,000 female population, which is 8.2 times higher than the detection rate of CC. All patients regardless of CIN degree underwent loop electrosurgical excision (LEEP)/conization. In the follow-up period (6-48 months), complete recovery after 136 LEEP, 21 conizations, and 7 hysterectomies were observed in 97% (5 recurrences of non-invasive disease). CONCLUSION: The visual screening showed high efficiency in detecting CIN. The positive experience suggests the implementation of this program nationwide.

Association between serum P16ink4A concentration and CIN and cervical cancer among women attending a cervical cancer clinic in western Uganda: A case control study

IntroductionTissue expression of P16ink4A is correlated with cervical lesions. In this study we determined the association between serum P16ink4A concentrations and cervical lesions among women attending the cervical cancer clinic at Mbarara Regional Hospital (MRRH) South Western Uganda. Material and MethodsWe recruited 90 cervical intraepithelial neoplasia (CIN) cases, 90 cervical cancer (CC) cases before treatment and 90 controls. Clinical and demographic data were recorded. Serum P16ink4A concentrations were measured by quantitative Elisa. Cases were confirmed with cytology and/or histology. Descriptive statistics and logistic regression were done with STATA 17 and P-values of <0.05 were considered statistically significant. ResultsThe mean serum P16ink4A concentration among CIN cases, CC cases and controls was 1.11(+/−0.66) ng/ml, 1.45(+/−1.11) ng/ml and 1.13(+/−0.61) ng/ml respectively (p = 0.008). 50 % of CIN cases and controls as well as 60 % of CC cases had P16ink4A concentration above 0.946 ng/ml. There were increased odds of CIN for serum P16ink4A though statistically insignificant (AOR: 1.11, p-value: 0.70). There was also a statistically significant reduction in odds of CC for serum P16ink4A (AOR: 0.55, p-value: 0.01). ConclusionSerum P16ink4A may likely be associated with cervical lesions especially CC in our study population and this may aid detection of such lesions. Diagnostic utility studies for circulating P16ink4A in detection of cervical cancer are recommended.

The changing nature of HPV associated with high grade cervical lesions in vaccinated populations, a retrospective study of over 1700 cases in Scotland.

Understanding the pattern and dominance of HPV types in high grade cervical disease within increasingly vaccinated populations will help inform the development of appropriate screening and management protocols. Over 1700 cases of cervical intraepithelial neoplasia (CIN) diagnosed between 2011 and 2017 in women younger than 25 were genotyped for HPV. Logistic regression was used to assess the association between HPV 16/18 positivity with biopsy-collection year, birth year, deprivation and vaccination status. Regression analysis was repeated for cross-protective types (31, 33 and 45). Type specific detail of non-vaccine types by vaccination status was presented descriptively. Detection of HPV 16/18 or 16/18/31/33 and 45 was lower in CIN2 associated with full vaccination vs no vaccination (OR 0.3; 95% CI 0.2-0.5 & 0.4; 95% CI 0.3-0.6 respectively) Similar observations were made for CIN3. The relative contribution of non-established high-risk types including those considered low risk was greater among vaccinated women with CIN2+ vs unvaccinated women with CIN2+. The change in HPV distribution in CIN2+ in vaccinated populations is a further marker of vaccine impact. Additionally, the progression rate of CIN2+ in vaccinated populations may be lower given the shift in type distribution. The definition of high grade disease in vaccinated populations may warrant reassessment.

The Value of Four-Quadrant Cervical Biopsy in Women with Different Colposcopic Impressions.

The aim of this study was to compare the diagnostic efficacy of colposcopic-directed biopsy and four-quadrant biopsy in detecting high-grade cervical intra-epithelial neoplasia (CIN). Women attending three women's clinics for routine cervical screening were recruited. Colposcopy was arranged for women with any cytologic abnormalities greater than atypical squamous cells of undetermined significance (ASCUS), two consecutive ASCUS results or positive HPV testing. During colposcopy, a cervical biopsy was taken from the most suspicious area, but more than one biopsy was allowed. Four-quadrant biopsies at 3, 6, 9 and 12 o'clock and an endocervical curettage were also taken in all cases. A total of 1522 colposcopies were performed in 1311 subjects from June 2010 to August 2017, with 118 cases of high-grade CIN diagnosed. Colposcopic-directed biopsy detected 50.8% of the 118 high-grade CIN, while four-quadrant biopsy detected 86.4% (p < 0.0001). Twenty-seven cases (22.9%) of high-grade CIN were diagnosed in women with normal or unsatisfactory colposcopy. Among the 64 cases with low-grade colposcopic impression, four-quadrant biopsy detected significantly more high-grade CIN (53 cases, 82.8%) than colposcopic-directed biopsy (35 cases, 56.3%) (p = 0.0011). Four-quadrant cervical biopsies should be considered for all women with an abnormal smear or positive HPV testing, especially in patients with low-grade/normal/unsatisfactory colposcopy.

The cytological pattern of cervical smears of a series of Saudi women in one gynecologic center.

Cervical intraepithelial neoplasia (CIN) is a type of abnormal cervical epithelial development that can lead to cervical malignancy. Thus, the purpose of this study was to examine the cytological pattern of cervical smears from a group of Saudi women who visited a single gynecologic center. From May 2020 to May 2021, 300 women were referred to the cytopathology laboratory and their cytological materials were collected. Because of gynecologic concerns, the women in the study were referred for Pap smears. As part of the obligatory investigations in conjunction with the clinical assessment, a Pap smear is requested. CIN of various grades was found in 11% of the women. High-grade Squamous Intraepithelial Lesions (HSIL) were the most detected modifications, followed by Atypical Squamous Cells of Undetermined Significance (ASUS) and Low-grade Squamous Intraepithelial Lesions (LSIL), accounting for 36.4%, 33.3%, and 30.3%, respectively. In 23.7% of the women, inflammatory cell infiltrations were found. Infection with Candida Albicans was identified in 2.3% of the women. In 15.8% of the patients, cytological evidence of bacterial infection was found. The prevalence of CIN has been growing in Saudi Arabia in recent years, implying a probable involvement in the spread of HPV. Most CIN cases associated with middle age point to HPV infection at a younger age. There is no link between estrogen and/or progesterone levels and CIN.

Epidemiological features of the incidence of cervical intraepithelial neoplasia in the modern megapolis

Background. Information on the incidence of cervical intraepithelial neoplasia (CIN) is relevant for planning and evaluating the effectiveness of medical care at the stage of secondary prevention of cervical cancer. Aim. To analyze the incidence of CIN and benign diseases of the cervix: erosion and ectropion, leukoplakia, polyp, according to medical organizations in Yekaterinburg in 2013–2019. Materials and methods. A descriptive epidemiological study of the incidence of cervical pathology in the population of women in Yekaterinburg in 2013–2019 was conducted. The forms of Federal Statistical Observation No. 12 “Information on the number of diseases registered in patients living in the service area of a medical organization”, in terms of erosion and ectropion, and data from the city’s women’s consultations on the number of cases of CIN, leukoplakia and cervical polyp were examined. Information on the number of female population of the city from Sverdlovskstat was used. Results. The primary incidence of CIN increased throughout the follow-up period. The indicator increased by 1.7 times compared to 2013 (p &lt; 0.001) in 2016, it had a maximum value in 2019 – 215.5 per 100 thousand women and was 3.2 times more than in 2013 (p &lt; 0.001). The dynamics of the primary incidence of other types of cervical pathology: ectropion, leukoplakia and cervical polyp, was characterized by the absence of significant changes (p &gt; 0.05) in 2013–2019. The increase in the overall incidence of CIN was registered from 2014 to 2019 in comparison with 2013 (p &lt; 0.001). The indicator of the overall incidence of CIN in 2019 was 2.1 times higher than in 2013 (p &lt; 0.001). Conclusions. The growth of primary and total incidence of CIN in the population of Yekaterinburg women noted since the beginning of the XXI century continued in 2013–2019. The primary incidence rate of CIN had the maximum value in 2019. The increase in the incidence of CIN is associated with the natural spread of the disease, accessibility and improvement in the quality of medical care.

Spectrum, Clinicopathologic Profile, and p16 Expression Pattern of Nonmalignant Cervical Tissues in Enugu, South-East Nigeria

Abstract Background p16 is a marker for p16-induced transformation of high-risk human papilloma virus (hrHPV)-infected cervical epithelium. HPV is a known etiologic agent of cervical cancer. Persistent hrHPV infection of cervical epithelium causes transformation of the infected epithelial cells resulting in increased proliferative potential of the cells and subsequent progression to frank malignancy. Early detection of transformation in cervical cells is crucial in reducing morbidity and mortality associated with cervical cancer. Materials and Methods We aimed to study the clinicopathologic profile of nonmalignant cervical lesions and their p16 staining pattern. Histopathology requisition forms, blocks, and slides of cases containing cervical tissue with nonmalignant diagnosis received into the morbid anatomy department of University of Nigeria Teaching Hospital, Enugu, from 2009 to 2018 were studied. Fresh sections from the blocks were immunohistochemically stained with p16 and examined. Results One-hundred and ninety-one cases were studied. Majority of the cases are normal cervical epithelium. Chronic nonspecific cervicitis was the major non-neoplastic lesion present and accounted for 33.3% of the biopsy and the mean age was 50.5 years. Other lesions were nabothian cyst (8.4%), cervical polyp (10.5%), low-grade and high-grade squamous intraepithelial lesion (LSIL and HSIL; 6.3 and 2.6%, respectively). The mean age for LSIL was 40.3 years, while that of HSIL was 45.2years. Four LSIL, two HSIL, one polyp, one chronic nonspecific cervicitis, and one lobular endocervical hyperplasia stained positively with p16. Conclusion The most common benign lesion of the cervix is cervicitis. Chronic cervicitis is negative to p16 immunoreactivity. There are more low-grade cervical intraepithelial neoplasia (CIN) than high-grade CIN. The low-grade CIN overexpress p16 in one-third of cases. There are more cases of p16-negative high-grade CIN in this study.

Morphometric Features of Cells of Cervical Intraepithelial Neoplasia Using Computer Aided Image Analysis

Aim: Our goal is to evaluate and compare the different cell morphometric parameters in the various categories of cervical intraepithelial neoplasia (CIN).&#x0D; Study Design: We conducted a cross-sectional study of all cervical intraepithelial neoplasia identified in some areas of biopsies of cervical carcinomas.&#x0D; Place and Duration of Study: The study was in the department of histopathology of LAUTECH Teaching Hospital, Osogbo from January 2006 to December 2015.&#x0D; Materials and Methods: The histologic slides produced were scanned using CS2 APERIO digital slide scanner with standard settings. The scanned slides were then viewed using Qu Path-0.3.2 software. All areas of cervical intraepithelial neoplasia were selected. The perimeter, area, maximum caliper, circularity, eccentricity, and the various measures of hematoxylin optic densities (OD) of the nucleus of the cells were measured. The cytoplasmic morphometric measurements and the nuclear-cell ratio were then estimated.&#x0D; Results: Two cases of CIN 1, one case of CIN 2 and one case of CIN 3 were seen in the background of the eighty-seven cases of cervical carcinomas seen during the study period. A total of 5,935 cells were in the annotated regions with cervical intraepithelial neoplasia. The cells in CIN 1 area are 3,828, CIN 2 area has 1183 cells and CIN 3 areas has 924 cells. Cells of CIN 3 had higher average nuclei hematoxylin optic density (OD), nuclei hematoxylin OD standard deviation and maximum hematoxylin OD than cells of CIN 2 and CIN 1. Cells of CIN 1 have higher average cell area, cell perimeter, cell circularity and mean cytoplasm eosin OD compared to cells of CIN 2 and 3.&#x0D; Conclusion: Computer-aided image analysis using Qu Path software can be very instrumental in differentiating the various categories of cervical intraepithelial neoplasia especially in fragmented biopsies.

Adjuvant Human Papillomavirus Vaccination After Excisional Procedure for Cervical Intraepithelial Neoplasia: A Cost-Effectiveness Analysis.

To examine the cost effectiveness of human papillomavirus (HPV) vaccination after excisional procedure compared with no vaccination. We constructed a decision-analytic model (TreeAge Pro 2021) to compare outcomes between patients who underwent an excisional procedure followed by nonavalent HPV vaccination to those who underwent an excisional procedure without vaccination. Our theoretical cohort contained 250,000 patients, the approximate number undergoing excisional procedures annually in the United States. Our outcomes were costs, quality-adjusted life-years (QALYs), recurrence events, number of surveillance Pap tests with co-testing, number of colposcopies, and second excisional procedures. Probabilities of recurrence were based on a recently published meta-analysis. All values were derived from the literature, and QALYs were discounted at a rate of 3%. Outcomes were applied for 4 years after the initial excisional procedure. Our cost-effectiveness threshold was $100,000 per QALY. Sensitivity analyses were performed to evaluate the robustness of the model. In our theoretical cohort of patients who underwent an excisional procedure, the HPV vaccination strategy was associated with 17,281 fewer recurrences of cervical intraepithelial neoplasia (CIN) (8,360 fewer cases of CIN 1 and 8,921 fewer cases of CIN 2 or 3), 26,203 fewer Pap tests (1,025,368 vs 1,051,570), 17,281 fewer colposcopies (20,588 vs 37,869), and 8,921 fewer second excisional procedures (4,779 vs 13,701). The vaccination strategy was associated with a higher cost of $135 million. Vaccination was a cost-effective strategy, with an incremental cost-effectiveness ratio of $29,181 per QALY, compared with no vaccination. In our sensitivity analyses, the HPV vaccination strategy remained cost effective until the cost of the three-dose HPV vaccine series reached $1,899 or the baseline (nonvaccinated) probability of recurrence was less than 4.8%. In our model, HPV vaccination for patients with a prior excisional procedure led to improved outcomes and was cost effective. Our study suggests that clinicians should consider offering the three-dose HPV vaccine series to patients who have undergone an excisional procedure to decrease the risk of CIN recurrence and its sequelae.

Promoter hypermethylation analysis of host genes in cervical intraepithelial neoplasia and cervical cancers on histological cervical specimens

BackgroundDNA methylation is an essential factor in the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer. The aim was to investigate the diagnostic value provided by methylation biomarkers of six tumor suppressor genes (ASTN1, DLX1, ITGA4, RXFP3, SOX17 and ZNF671) for cervical precancerous lesions and cervical cancer.MethodsThe histological cervical specimens of 396 cases including 93 CIN1, 99 CIN2, 93 CIN3 and 111 cervical cancers were tested for methylation-specific PCR assay (GynTect®) of score and positive rate. Among them, 66 CIN1, 93 CIN2, 87 CIN3 and 72 cervical cancers were further used for paired analysis. A chi-square test was used to analyze the difference of methylation score and positive rate in cervical specimens. The paired t-test and paired chi-square test were for analyzing the methylation score and positive rate in paired CIN and cervical cancer cases. The specificity, sensitivity, odds ratio (OR) and 95% confidence interval (95% CI) of the GynTect® assay for CIN2 or worse (CIN2 +) and CIN3 or worse (CIN3 +) were evaluated.ResultsAccording to the chi-square test trend, hypermethylation increased with severity of the lesions as defined by histological grading (P = 0.000). The methylation score above 1.1 was more common in CIN2 + than in CIN1. The DNA methylation scores in the paired groups of CIN1, CIN3 and cervical cancer were significant differences (P = 0.033, 0.000 and 0.000, respectively), except for CIN2 (P = 0.171). While the positive rate of GynTect® in each paired group had no difference (all P > 0.05). The positive rate of every methylation marker in the GynTect® assay showed differences in four cervical lesion groups (all P < 0.05). The specificity of GynTect® assay for detection of CIN2 + /CIN3 + were higher than high-risk human papillomavirus test. With CIN1 as a reference, the positive status of GynTect®/ZNF671 were significantly higher in CIN2 + : odds ratio (OR) 5.271/OR 13.909, and in CIN3 + : OR 11.022/OR 39.150, (all P < 0.001).ConclusionThe promoter methylation of six tumor suppressor genes is related to the severity of cervical lesions. The GynTect® assay based on cervical specimens provides diagnostic values for detecting CIN2 + and CIN3 + .

The Clinical and Economic Impact of a Nonavalent Versus Bivalent Human Papillomavirus National Vaccination Program in Taiwan

This study aimed to estimate the epidemiologic and economic impact of a nonavalent human papillomavirus (HPV) vaccination program for 13- to 14-year-old females compared with that of the bivalent vaccine in Taiwan. A previously developed dynamic transmission model for the nonavalent HPV vaccine was adapted to the Taiwan setting. The natural history of cervical cancer and genital warts was simulated by the HPV model assuming an 80% vaccination coverage rate in girls aged 13 to 14 years of age with a 2-dose schedule for the nonavalent and bivalent HPV vaccines. A lifetime duration of vaccine protection was assumed for the HPV vaccine types. The model estimated that the nonavalent HPV vaccine would prevent an additional 15 951 cervical cancer cases, 6600 cervical cancer-related deaths, 176 702 grade 2 or grade 3 cervical intraepithelial neoplasia cases, 103 959 grade 1 cervical intraepithelial neoplasia cases, and 1 115 317 genital warts cases compared with the bivalent HPV vaccine. The nonavalent HPV vaccination program was projected to cost an additional New Taiwan dollars (NTD) 675.21 per person and to produce an additional 0.00271 quality-adjusted life-year per person over 100 years compared with the bivalent HPV vaccine. Thus, the incremental cost-effectiveness ratio of the nonavalent HPV vaccine versus the bivalent HPV vaccine was NTD 249 462/quality-adjusted life-year. A nonavalent HPV vaccination program for 13- to 14-year-old girls would have additional public health and economic impacts and would be highly cost-effective compared with the bivalent HPV vaccine, relative to per capita gross domestic product, which is estimated at NTD 746 526 for Taiwan.

Absence of high-grade cervical intraepithelial neoplasia in conization specimens from patients with colposcopic biopsy-confirmed high-grade cervical intraepithelial neoplasia: Retrospective study of 1695 cases.

Few studies have investigated the absence of high-grade cervical intraepithelial neoplasia (CIN) in excised specimens, and sample sizes of these studies were limited. This study retrospectively analyzed clinical characteristics of 1695 patients with CIN 2/3 to determine the incidence rate and relative factors of CIN 1 or less in conization specimens from patients with colposcopic biopsy-confirmed CIN 2/3. The study group comprised 430 cases of CIN 1 or less in conization specimens, and the control group comprised 1142 cases with high-grade CIN lesions in conization specimens. Univariate and multivariate logistic regression models were established to evaluate relative factors. The 1–9 years follow-up data were analyzed to determine the persistence/recurrence rate. Multivariate logistic regression showed that patients aged 18–24 years (OR (95% CI) = 2.224 (1.014, 4.877)); with a negative hrHPV test result (OR (95% CI) = 3.210 (1.627, 6.331)); a cytology test result of normal (OR (95% CI) = 5.184 (3.138, 8.563)), ASC-US (OR (95% CI) = 3.420 (2.102, 5.564)), LSIL (OR (95% CI) = 2.588 (1.475, 4.541)), or ASC-H (OR (95% CI) = 2.434 (1.306, 4.539)); an indication of CIN 2 on biopsy (OR (95% CI) = 2.290 (1.694, 3.096)), and no glandular involvement (OR (95% CI) = 1.616 (1.205, 2.169)) were more likely to have an absence of high-grade dysplasia in conization specimens. There was no difference in the persistence/recurrence rate between the two groups (x2 = 1.55, P = 0.46). An age of 18–24 years, a negative hrHPV test result, a non-HSIL cytology test result, an indication of CIN 2 on biopsy, and no glandular involvement were relative factors for an absence of high-grade dysplasia in conization specimens. For patients with relative factors, especially young women, informed follow-up should be considered.

Low erythrocyte folate levels and increased risk of invasive cervical cancer in Chinese women

To investigate the relationship between erythrocyte folate levels and cervical lesions. Using a case-control method, patients with cervical lesions from September 2021 to February 2022 in the Department of Obstetrics and Gynecology, Jiangnan University Hospital were selected as study subjects. After cervical biopsy, 40 cases of cervical intraepithelial neoplasia (CIN) CIN3 and 65 cases of cervical cancer as case group. The normal population of 120 cases attending the same period served as the control group. A competitive model was used to establish a chemiluminescence immunoassay (CLIA) for human erythrocyte folate. Erythrocyte folate levels of 225 subjects were determined. Serum folate levels were 7.82 ± 3.13, 8.04 ± 3.58, and 7.58 ± 4.30 ng/ml in the control, CIN3, and cervical cancer groups, with no statistically significant differences (p=0.959). Erythrocyte folate levels were 307.27 ± 122.95, 306.52 ± 189.77, and 285.42 ± 125.74 ng/ml, respectively, with statistically significant differences (p=0.03). In a population of middle-aged Chinese women, the lower the erythrocyte folate value, the greater the risk of cervical cancer. In addition, serum folate levels were not associated with cervical lesions.

HPV vaccination following loop electrical excision procedure (LEEP) for cervical intraepithelial neoplasia: A cost-effectiveness analysis (134)

Objectives: Excisional cervical procedures, such as a Cold Knife Cone (CKC) or a loop electrical excision procedure (LEEP), are standard treatments for moderate to severe cervical intraepithelial neoplasia (CIN). Human papillomavirus (HPV) is the causal agent for CIN and can persist or recur; thus, patients can be susceptible to recurrent CIN following excision. Some data suggest that CIN recurrence rates decrease with HPV vaccination after LEEP. Here, we aimed to examine the cost-effectiveness of HPV vaccination following LEEP procedures compared with no vaccination. Methods: We constructed a decision-analytic model (TreeAge Pro 2021) to compare outcomes between patients who underwent LEEP followed by HPV vaccination with those who underwent LEEP without HPV vaccination. Our theoretical cohort contained 250,000 patients, the approximate number of patients who had LEEPs per year in the United States. Our outcomes were costs, quality-adjusted life-years (QALYs), any recurrence, recurrence of CIN 1, recurrence of CIN 2/3, number of pap smears, colposcopy, and second LEEP. We assumed that all individuals with any recurrence underwent a colposcopy and that all individuals who had a recurrence of CIN 2/3 would undergo a second LEEP. Probabilities of recurrence were based on a recently-published meta-analysis. All values were derived from the literature and discounted QALYs at a rate of 3%. Utilities were applied for four years after the initial LEEP procedure. Our cost-effectiveness threshold was $100,000/QALY. Univariate sensitivity analyses were performed to evaluate the robustness of the model. Results: In our one-year theoretical cohort of 250,000 patients who had undergone LEEP, the HPV vaccination strategy was associated with 17,281 fewer recurrences of CIN (8,360 cases of CIN 1 and 8,921 cases of CIN 2/3), 26,203 fewer pap smears (1,025,368 vs 1,051,570), 17,281 fewer colposcopies (20,588 vs 37,869), and 8,921 fewer second LEEP procedures (4,779 vs 13,701) (Table 1). The vaccination strategy was associated with a higher cost of $135 million. However, HPV vaccination was the cost-effective strategy with an incremental cost-effectiveness ratio (ICER) of $29,180.81. In our sensitivity analyses, the HPV vaccination strategy remained cost-effective until the cost of the 3-dose HPV vaccine series reached $1,899.56, or the baseline (non-vaccinated) probability of recurrence was less than 4.8%. Objectives: Excisional cervical procedures, such as a Cold Knife Cone (CKC) or a loop electrical excision procedure (LEEP), are standard treatments for moderate to severe cervical intraepithelial neoplasia (CIN). Human papillomavirus (HPV) is the causal agent for CIN and can persist or recur; thus, patients can be susceptible to recurrent CIN following excision. Some data suggest that CIN recurrence rates decrease with HPV vaccination after LEEP. Here, we aimed to examine the cost-effectiveness of HPV vaccination following LEEP procedures compared with no vaccination. Methods: We constructed a decision-analytic model (TreeAge Pro 2021) to compare outcomes between patients who underwent LEEP followed by HPV vaccination with those who underwent LEEP without HPV vaccination. Our theoretical cohort contained 250,000 patients, the approximate number of patients who had LEEPs per year in the United States. Our outcomes were costs, quality-adjusted life-years (QALYs), any recurrence, recurrence of CIN 1, recurrence of CIN 2/3, number of pap smears, colposcopy, and second LEEP. We assumed that all individuals with any recurrence underwent a colposcopy and that all individuals who had a recurrence of CIN 2/3 would undergo a second LEEP. Probabilities of recurrence were based on a recently-published meta-analysis. All values were derived from the literature and discounted QALYs at a rate of 3%. Utilities were applied for four years after the initial LEEP procedure. Our cost-effectiveness threshold was $100,000/QALY. Univariate sensitivity analyses were performed to evaluate the robustness of the model. Results: In our one-year theoretical cohort of 250,000 patients who had undergone LEEP, the HPV vaccination strategy was associated with 17,281 fewer recurrences of CIN (8,360 cases of CIN 1 and 8,921 cases of CIN 2/3), 26,203 fewer pap smears (1,025,368 vs 1,051,570), 17,281 fewer colposcopies (20,588 vs 37,869), and 8,921 fewer second LEEP procedures (4,779 vs 13,701) (Table 1). The vaccination strategy was associated with a higher cost of $135 million. However, HPV vaccination was the cost-effective strategy with an incremental cost-effectiveness ratio (ICER) of $29,180.81. In our sensitivity analyses, the HPV vaccination strategy remained cost-effective until the cost of the 3-dose HPV vaccine series reached $1,899.56, or the baseline (non-vaccinated) probability of recurrence was less than 4.8%.

Expression of p63 in Cervical Intraepithelial Neoplasia (CIN) and Cervical Cancer

Background: Cervical cancer is a major public health problem worldwide. Persistent infection with High-Risk Human Papilloma Virus (HPV) has been the main cause of squamous intraepithelial neoplasia which in turn leads to invasive squamous cell carcinoma. p63 is necessary for the activation of HPV, epithelial proliferation and differentiation. It also regulates the expression of certain cell cycle regulators. It has been reported that, from CIN I to CIN III, p63 expression increases progressively from basal layer to surface. In squamous cell carcinoma, it is expressed throughout the entire thickness of the tumor. Thereby it plays a significant role in diagnosing cervical premalignant and malignant lesions.&#x0D; Objective: To evaluate the relationship of p63 expression with different grades of CIN &amp; invasive SCC.&#x0D; Method: Total 86 paraffin embedded tissue blocks of histopathologically diagnosed cases of CIN and cervical cancer were evaluated by immunohistochemical staining for p63 expression. The study was performed in Sir Salimullah Medical College, Dhaka (from March, 2018 to February, 2020). Statistical analyses were carried out by using SPSS version 22 for Windows. A descriptive analysis was performed for all data. Observations were indicated by frequencies and percentages. Statistical significance was set at “p” value &lt;0.05.&#x0D; Results: Present study showed progressive increase in p63 expression from CIN I to CIN III from basal layer to surface. In invasive squamous cell carcinoma, higher expression of p63 was noted throughout the entire thickness of the tumor. No expression was seen in cervical adenocarcinoma and small cell carcinoma. In adenosquamous carcinoma only the area showing squamous differentiation revealed positive p63 expression. Statistically significant association of p63 expression was found with parity of patients and among grades of CIN .&#x0D; Conclusion: The results of this current study revealed that, p63 has significant association among different grades of CIN. It is also a useful marker in confirming a poorly differentiated squamous cell carcinoma &amp; predicting the progression of a squamous neoplastic lesion from cervical intraepithelial neoplasia to invasive squamous cell carcinoma. Moreover, it is useful to differentiate invasive squamous cell carcinoma from cervical adenocarcinoma.&#x0D; Sir Salimullah Med Coll J 2021; 29(2): 141-146

The eight-year long-term follow-up on the effectiveness of the quadrivalent human papillomavirus vaccine in Chinese women 20-45 years of age

ABSTRACT The quadrivalent human papillomavirus (4vHPV) vaccine has shown confirmative effectiveness in preventing HPV-related diseases among women and men around the globe. The phase III, randomized, double-blind efficacy study (Base study, NCT00834106) conducted in China showed 100% efficacy against HPV 16/18-related cervical intraepithelial neoplasia and efficacy against HPV persistent infection for 78 months. Participants aged 20–45 years who received three doses of 4vHPV vaccine or placebo during the base study were selected and invited for this long-term follow-up (LTFU) study to assess the long-term effectiveness of the 4vHPV vaccine in preventing HPV-related diseases. A total of 368 participants were included in this LTFU study with a median follow-up of 94 months. Among 27 participants (Vaccine vs. Placebo: 8 vs. 19) who underwent colposcopy and biopsy due to cervical cytological abnormalities or HPV infection, no HPV-16/18-related cases of cervical intraepithelial neoplasia (CIN), vulvar intraepithelial neoplasia (VIN), or vaginal intraepithelial neoplasia (VaIN) was observed in the vaccine group while two HPV-16-related cases (CIN1/VaIN) were observed in the placebo group. There were another two HPV-related cases (non-vaccine HPV types) found in the placebo group. Consistent with the findings from global studies that suggested long-term efficacy of 4vHPV vaccine, our study showed continued protective effect of 4vHPV vaccine against HPV-related precancerous diseases through a median follow-up time of 94 months with the longest follow-up time of 125 months after completing three doses of vaccination among Chinese women 20–45 years of age.

Prevalence of High-Risk Human Papillomavirus in Cervical Intraepithelial Neoplasia in the Pre-Vaccine Era - China, 2017-2018.

Human papillomavirus (HPV) type-specific strategies play a key role in the prevention of cervical intraepithelial neoplasia (CIN), but evidence on the HPV type-specific prevalence in CIN is limited. This multicentric study estimates the prevalence of high-risk HPV types in CIN cases and the associations of HPV infection patterns with high-grade CIN in China in 2017-2018. Population-based prevention strategies should give preference to HPV-16 and 18, and strategies for non-16/18 high-risk HPV are essential for the elimination of cervical cancer.

The immunohistochemical biomarker B-cell lymphoma-2 expression in malignant and premalignant lesions of the uterine cervix and its association with human papillomavirus infection.

Cervical cancer is one of the leading causes of cancer deaths among women. It results due to human papillomavirus (HPV) infection. Cervical intraepithelial neoplasia (CIN) is the preinvasive condition of cervical cancer. Various objective immunohistochemical (IHC) markers have been studied for cervical cancer. This study is aimed at studying the expression of B-cell lymphoma-2 (Bcl-2) IHC marker among preinvasive and invasive lesions of cervical cancer and its association with HPV infection. This prospective study was conducted over a period of 1 year in a tertiary care hospital in central India, included 73 women suffering from CIN and cancer cervix. The expression of Bcl-2 and the presence of HPV genotypes were studied. Out of 73 patients, 34 had cancer cervix, out of which 15 (44%) had Bcl-2 positivity, 24 had CIN 1, out of which 13 (54%) had Bcl-2 positivity, 10 had CIN 2, out of which 4 (40%) had Bcl-2 positivity and 5 had CIN 3, out of which 3 (60%) had Bcl-2 positivity. No significant difference was found in Bcl-2 positivity among CIN-1, CIN-2, CIN-3, and cancer cervix cases with a Chi-square value of 1.116 and P = 0.77. HPV positivity was found in 41 (56%) out of 73 patients where HPV 16 subtype was the most common (31.5%), followed by HPV 18 (13.7%). No significant association between HPV positivity and Bcl-2 positivity was found with P = 0.34. Bcl-2 IHC seems to have variable expression among CIN cases. Although its expression is low among invasive cancer cases when compared with preinvasive lesions, the difference is not significant. Similarly, no significant association was found between Bcl-2 expression and HPV infections.

ROC-Analysis Derived Immunohistochemical P53 Cut-Off Scores as an Adjunct to Routine Histopathology for Better Diagnostic Compartmentalisation of Cervical Lesions.

ObjectiveThe aim of this study was to evaluate the predictive value of Immunohistochemical p53 cut-off scores as an adjunct to routine histopathology for better diagnosis of cervical lesions.Materials and MethodsProspective study carried out for 1 year. After ethical approval and informed consent, a total of 100 cervical tissue samples were analyzed; chronic cervicitis (CC)-15, cervical intraepithelial neoplasia (CIN)-40, and squamous cell carcinoma cervix (SCC)-45 (FIGO 2018 clinical staging). After routine processing of tissue specimen, hematoxylin and eosin (HE) staining was done. Grading of cervical precancerous lesions (CIN) was done as per World Health Organisation criteria as CIN 1,2 or 3. Broder’s grading was assigned for every SCC sample.ResultsMean p53 scores of CC, CIN, and SCC cases were 0.0, 1.70, and 4.38, respectively, CIN 1, 2, and 3 were 1.07, 1.63, and 2.22, respectively. SCC was differentiated from CIN3 with p53 ≥4.5 as predictor for SCC, sensitivity and specificity were 57.8% and 88.9%, respectively. Overall diagnostic accuracy of the proposed scoring system for differentiating CC, CIN, and SCC was 61%, while the accuracy of previous methods of interpreting p53 immunoreactivity as immunoscore >2 or arbitrary cut-off of >10% cells with nuclear positivity was only 48%.ConclusionROC-derived immunoscore cut-offs can provide the much-needed objectivity and optimal decision thresholds to immunohistochemistry interpretation.