Squamous Lesions Research Articles

Analysis of the Results of Severe Intraepithelial Squamous Cell Lesions and Preinvasive Cervical Cancer Phototheranostics in Women of Reproductive Age.

(1) Purpose: To investigate the efficacy and safety of using PDT in the treatment of severe intraepithelial squamous lesions of the cervix and preinvasive cervical cancer associated with HPV in women of reproductive age. (2) Methods: The examination and treatment of 45 patients aged 22–49 years with morphologically confirmed HPV-associated cervical intraepithelial neoplasia of a severe degree (17 patients) and preinvasive cervical cancer (28 patients) were performed. All patients underwent PDT of the cervix using a chlorin e6 photosensitizer; after which, the affected areas of the cervix were evaluated using video and spectral fluorescence diagnostics. PDT effectiveness was assessed on the basis of colposcopy data, a cytological examination of exo- and endocervix and PAP test scrapings or the liquid cytology method, and polymerase chain reaction for HPV carriage 4 weeks after PDT, as well as on the basis of histological and immunohistochemical studies of biopsy materials 5 weeks after PDT. The expression levels of the Ki-67 and p16 markers in the affected areas of the cervix were also assessed. (3) Results. All patients included in the study tolerated the intravenous administration of the photosensitizer well, with no side effects or allergic reactions observed. In 88.2% of patients with CIN III/HSIL and in 85.7% of women with preinvasive cervical cancer, the effect of the treatment was noted after the first PDT procedure, while complete regression of the dysplasia foci was observed in 15 women (88.2%) with CIN III/HSIL and in 25 patients (89.3%) with preinvasive cervical cancer. Partial regression to the form of LSIL/CIN I was noted in two cases (11.8%) in the CIN III/HSIL group and in three cases (10.7%) in the group of patients with preinvasive cervical cancer. After PDT, a statistically significant decrease in the expression of the Ki-67 and p16 levels relative to the initial values was noted. (4) Conclusions. The results obtained indicate the high efficiency of PDT with intravenous administration of the chlorin photosensitizer for the treatment of intraepithelial lesions of the cervix with a selective effect on pathologically altered tissue. The use of this approach makes it possible to preserve the normal anatomical and functional characteristics of the cervix, which is especially important for maintaining the fertility of patients.

Concordance Rate of Colposcopy in Detecting Cervical Intraepithelial Lesions.

Background: The purpose of this research is to estimate the rate of concordance, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of colposcopy for high-grade squamous lesions and carcinomas (HSIL+). Methods: We conducted a retrospective study of colposcopies performed in the certified Dysplasia Unit in Erlangen between January 2015 and May 2022 (7.5 years). The colposcopic findings were correlated with biopsies obtained during examinations or surgery. Cases without histology were excluded. The primary outcome was the rate of concordance between the colposcopic and histological findings in relation to the type of transformation zone (TZ), examiner’s level of experience and age of the patients. Results: A total of 4778 colposcopies in 4001 women were analyzed. The rates of concordance for CIN I/LSIL, CIN II/HSIL, CIN III/HSIL, and carcinoma were 43.4%, 59.5%, 78.5%, and 53.9%, respectively. The rate of concordance was lowest for TZ3 and highest for colposcopists with more than 10 years’ experience. Conclusions: Colposcopy is an important, feasible, and effective method. Careful work-up needs to be performed for women with TZ3 who are over 35 years old, as they are at the highest risk of being misdiagnosed. The highest concordance for detecting HSIL+ was seen for colposcopists with >10 years’ experience.

48 Juvenile dermatomyositis: the experience of Military Pediatrics Department of Tunis

BackgroundJuvenile dermatomyositis (JD) is a rare autoimmune disorder characterized by a non-infectious inflammatory state affecting of the muscles and skin associated with a vasculopathy which represents the essential of its physiopathogenesis.ObjectivesTo review the clinical and biological diagnosis of DMJ as well as its evolution under treatment based on the cases of two patients at the Military Pediatrics Department of Tunis.ObservationsCase 1: This was a three-and-a-half-year-old child with a history of a simple febrile seizure, admitted for a skin rash and myalgia that had been evolving for eight months. Skin examination revealed an erythematous rash of the face and upper eyelids with erythematous papular lesions in front of the proximal interphalangeal joint recalling Gottron's papules. Muscle testing was in favor of a proximal deficiency and the electromyogram (EMG) revealed a diffuse myogenic process more pronounced on the proximal muscles without signs of myositic activity. Biology analysis did not reveal a biological inflammatory syndrome but rather increased muscle enzymes levels up to 3- and 4-times normal values. On the immune status report, there was no evidence of DMJ-specific autoantibodies (ASM), but the anti-SRP antibodies associated with myositis were present. The diagnosis of DMJ was established in view of the association of typical cutaneous signs and 3 muscular signs (proximal deficit, elevation of muscle enzymes, myogenic tracing) and an evaluation of the activity of the disease according to a standardized scale by the Childhood Myositis Assessment Scale (CMAS) was required (which was at 7/52). Treatment with corticosteroids and methotrexate was started after a pretherapeutic evaluation and regular check-ups of the child showed a clear improvement of clinical and muscular signs (CMAS became at 41/52). Case 2: A 7-year-old boy, with no previous pathological history, admitted to our department to explore his gait disorder associated to erythematosquamous lesions. At the dermatological inspection, a localized erythema was noted on the upper eyelids, the nose, the cheeks and the chin area, as well as erythematosquamous lesions on the interphalangeal joints, metacarpophalangeal joints, elbows and knees (Gottron papules). The gait was waddling, the EMG was in favor of myogenic disorder and the muscular testing revealed a proximal muscular affection. The biology results showed an elevation of CPK and LDH to 1.5 times the normal values and a sedimentation rate at 40 mm/h. The antibodies determination showed the existence of anti-NXP2 antibodies specific to myositis. The progression under treatment (corticosteroids, methotrexate and adjuvant treatment) was favorable with a CMAS score of 39 (CMAS was 11 when admitted). The persistence of squamous lesions recalling calcinosis on the dorsal surfaces of the forearms was well correlated with the presence of anti-NXP2 antibodies.ConclusionThe positive diagnosis of DMJ in a child must be based on clinical and biological arguments. The immunological characterization of DMJ should be an important element in the disease management because it can explain the lesions associated with certain myositis specific antibodies as well as their evolution, which implies a particular follow-up depending on the detected antibodies (risk of cancer in anti-NXP2 AC positive patients)

S2784 A Case of Delayed Cervical Cancer Diagnosis in a Patient With Crohn’s Disease

Introduction: Increased cancer risk in inflammatory bowel disease (IBD) is thought to be due to immunosuppression from biologic therapy and/or inflammation. Women with IBD have an increased risk of melanoma and adenocarcinoma of the small bowel and colon, and those that are on an immunosuppressive regimen that includes azathioprine have an additional increased risk of lymphoma and squamous cell carcinoma of the skin and cervix. Here we present a case of a patient with an atypical and rare malignancy, whose diagnosis was delayed due to overlap in the symptoms of the malignancy and her known IBD diagnosis. Case Description/Methods: A woman in her mid 40s with a 28-year history of colonic Crohn’s disease maintained on ustekinumab injection. She was previously taking azathioprine for 7 years and initially responded to adalimumab, but after a flare, was switched to ustekinumab with symptomatic and endoscopic response. She then presented to her gynecologist in November 2020 with complaints of bloating and large amounts of clear vaginal discharge. A cervical exam and routine pap smear of the ectocervix showed normal cytology. Eight months later, the patient presented to her gastroenterologist with worsening bloating, hematochezia, left lower quadrant pain, and persistent vaginal discharge. The patient was concerned for an IBD flare, but noted that the abdominal bloating and vaginal discharge were different than her usual flare. After CT abdomen/pelvis revealed 2 large pelvic complex cystic lesions, her biologic was stopped and she underwent a hysterectomy with bilateral salpingo-oophorectomy. Pathology revealed non-HPV associated invasive moderately differentiated gastric-type endocervical adenocarcinoma. She completed treatment with an anti-VEGF antibody, but a restaging PET scan six months later showed uptake consistent with peritoneal carcinomatosis. Discussion: This immunosuppressed patient had an advanced and aggressive non-HPV endocervical cancer which was missed on ectocervical pap smear. Pap smears that include inadequate endocervical samples are considered suboptimal, but are usually not grounds for further testing in the average patient. However, Crohn’s disease patients have increased risk of low- and high-grade squamous epithelial cervical lesions and cervical cancer compared to women without IBD, likely due to a combination of elevated inflammatory state and immunosuppressive medications. Cervical cancer screening in immunosuppressed patients with IBD should include adequate endocervical sampling.

Role of High-Risk HPV Testing in Papanicolaou Tests With Atypical Glandular Cells With and Without Concurrent Squamous Cell Abnormalities.

Data on Papanicolaou (Pap) tests with atypical glandular cells (AGCs) with concurrent squamous cell abnormalities (AGC + Sq) are limited. We evaluated histologic outcomes and the role of high-risk human papillomavirus (HR-HPV) testing in this setting compared with AGCs without concurrent squamous cell abnormalities (AGC-alone). This study used a retrospective cohort of patients with Pap test diagnoses of AGC + Sq and AGC-alone between October 2013 and August 2021. We included 287 Pap tests from 278 patients. The HR-HPV test was positive in 55% of AGC + Sq cases and 14% of AGC-alone cases (P < .0001). Most AGC + Sq cases displayed squamous lesions (41.5%) or were benign (41.5%) on histology, whereas AGC-alone cases were predominantly benign (72%) or extracervical neoplasms (18%). AGC + Sq cases showed higher rates of significant histologic lesions (P = .0001), which were associated with positive HR-HPV status (P = .0012). In AGC-alone cases, HR-HPV status was associated with significant histology only in patients 50 years of age or younger. In both groups, 20% or more of HR-HPV-negative patients harbored significant lesions. AGC + Sq represents a distinct group of patients. HR-HPV testing and patient age provide useful information in the evaluation of AGC, but triage based on HR-HPV testing is not recommended because of the potential for missing significant lesions.

PPARgamma agonism inhibits progression of premalignant lesions in a murine lung squamous cell carcinoma model.

The N-nitroso-trischloroethylurea (NTCU)-induced mouse model of squamous lung carcinoma recapitulates human disease from premalignant dysplasia through invasive tumors, making it suitable for preclinical chemoprevention drug testing. Pioglitazone is a peroxisome proliferator-activated receptor γ (PPARγ) agonist shown to prevent lung tumors in preclinical models. We investigated pioglitazone's effect on lesion development and markers of potential preventive mechanisms in the NTCU model. Female FVB/N mice were exposed to vehicle, NTCU or NTCU + oral pioglitazone for 32 weeks. NTCU induces the appearance of basal cells in murine airways while decreasing/changing their epithelial cell makeup, resulting in development of bronchial dysplasia. H&amp;E and keratin 5 (KRT5) staining were used to detect and grade squamous lesions in formalin fixed lungs. mRNA expression of epithelial to mesenchymal transition (EMT) markers and basal cell markers were measured by qPCR. Dysplasia persistence markers desmoglein 3 and polo like kinase 1 were measured by immunohistochemistry. Basal cell markers KRT14 and p63, club cell specific protein and ciliated cell marker acetylated tubulin were measured by immunofluorescence. Pioglitazone treatment significantly reduced squamous lesions and the presence of airway basal cells, along with increasing normal epithelial cells in the airways of NTCU-exposed mice. Pioglitazone also significantly influenced EMT gene expression to promote a more epithelial, and less mesenchymal, phenotype. Pioglitazone reduced the presence of squamous dysplasia and maintained normal airway cell composition. This work increases the knowledge of mechanistic pathways in PPARγ agonism for lung cancer interception and provides a basis for further investigation to advance this chemoprevention strategy.

HISTOPATHOLOGICAL STUDY OF NON-NEOPLASTIC LESIONS OF SKIN

Objectives: The objectives of the study were as follows: (1) To find the prevalence of various non-neoplastic skin lesions in our tertiary care hospital. (2) To study the age- and sex-wise distribution of non-neoplastic skin lesions. (3) To compare the results of the present study with other studies. Methods: The present study comprised total 200 punch biopsy specimens of diagnosed cases of non-neoplastic lesions of skin, detailed clinical data, age, sex, and sites of skin lesion of patients which were included in the study. Specimens received were fixed in 10% formalin. Biopsy bits were submitted as whole and processed in automated tissue processor for routine paraffin embedding. Results: A total of 200 lesions were analyzed. Maximum cases were in the age group of 21–30 years followed by 31–40 years age. Fifty-five (27.5%) cases were of non-infectious erythematous, papular, and squamous diseases followed by 54 (27%) cases of vesiculobullous and vesiculopustular diseases, 37 (18.5%) cases of bacterial diseases, 20 (10%) cases of fungal diseases, and 34 (17%) cases of vascular lesions, connective tissue disorders, non-infectious granulomas, perforating disorders, etc. Conclusion: Skin lesions were common in males than in females with male: female ratio of 1.38:1. Younger age group was more commonly affected. Non-infectious erythematous, papular, and squamous lesions were most common with psoriasis being the most common followed by non-infectious vesiculobullous and vesiculopustular lesions with pemphigus vulgaris being the most common, followed by infective lesions consisting of bacterial, fungal, and viral lesions. Other lesions consisted of vascular skin lesions, connective tissue disorders non-infectious granulomas, perforating disorders, etc.

FOXP4 inhibits squamous differentiation of atypical cells in cervical intraepithelial neoplasia via an ELF3-dependent pathway.

Although the human papillomavirus (HPV) vaccine is effective for preventing cervical cancers, this vaccine does not eliminate pre‐existing infections, and alternative strategies have been warranted. Here, we report that FOXP4 is a new target molecule for differentiation therapy of cervical intraepithelial neoplasia (CIN). An immunohistochemical study showed that FOXP4 was expressed in columnar epithelial, reserve, and immature squamous cells, but not in mature squamous cells of the normal uterine cervix. In contrast with normal mature squamous cells, FOXP4 was expressed in atypical squamous cells in CIN and squamous cell carcinoma lesions. The FOXP4‐positive areas significantly increased according to the CIN stages from CIN1 to CIN3. In monolayer cultures, downregulation of FOXP4 attenuated proliferation and induced squamous differentiation in CIN1‐derived HPV 16‐positive W12 cells via an ELF3‐dependent pathway. In organotypic raft cultures, FOXP4‐downregulated W12 cells showed mature squamous phenotypes of CIN lesions. In human keratinocyte‐derived HaCaT cells, FOXP4 downregulation also induced squamous differentiation via an ELF3‐dependent pathway. These findings suggest that downregulation of FOXP4 inhibits cell proliferation and promotes the differentiation of atypical cells in CIN lesions. Based on these results, we propose that FOXP4 is a novel target molecule for nonsurgical CIN treatment that inhibits CIN progression by inducing squamous differentiation.

Strategic Significance of Low Viral Load of Human Papillomavirus in Uterine Cervical Cytology Specimens.

Infection with high-risk (HR) Human Papillomavirus (HPV) is associated with the development of precancerous lesions or invasive carcinoma of the uterine cervix. Thus, the high viral load (VL) of HR-HPV DNA currently serves as a representative quantitative marker for cervical cancer. However, the clinical significance of low HPV DNA VL remains undetermined. This study aimed to evaluate the clinical association between the low HPV DNA VL and cytology/histologic diagnosis of cervical samples. We searched the electronic medical databases for the resultant analyses of HPV genotyping among patients who underwent treatment for any cervical lesion or who had undergone gynecological examinations with any positive HPV results according to the national cancer screening service between 2015 and 2016. HPV testing with genotyping and semi-quantitative VL measurement was conducted using an AnyplexTM II H28 Detection assay (H28 assay, Seegene, Seoul, Republic of Korea). The H28 assay is a multiplex semi-quantitative real-time PCR test using the tagging of oligonucleotide cleavage and extension (TOCE) technology. The VL was semi-quantified as high (3+; positive signal before 31 PCR cycles), intermediate (2+; positive between 31 and 39 PCR cycles), or low (1+; positive after 40 PCR cycles). Out of 5940 HPV VL analyses, 356 assays (5.99%) were reported as low VL (1+) of HPV DNA. Matched cytology diagnoses were mostly negative findings (n = 347, 97.5%), except for seven cases of atypical squamous cells of undetermined significance (1.9%) and two cases of atypical glandular cells (0.6%). During the follow-up periods, abnormal cytologic diagnoses were identified, including one case of high-grade squamous intraepithelial lesion (HSIL) and two low-grade squamous intraepithelial lesions (LSILs). The matched, confirmative histologic diagnosis of HSIL cytology was compatible with chronic inflammation, wherein the two LSILs had regular check-ups. None revealed clinically concerned outcomes associated with HPV-related squamous lesions. The cytology was most likely negative for malignancy when the VL of HPV DNA was low (1+). Additional strategic monitoring and management may thus be unnecessary.

MRI Using Artificial Intelligence Algorithm to Evaluate Concurrent Chemoradiotherapy for Local Recurrence and Distant Metastasis of Cervical Squamous Cell Carcinoma.

The aim of this study was to investigate the magnetic resonance imaging (MRI) features of patients with local recurrence and distant metastasis of cervical squamous cell carcinoma before and after concurrent chemoradiotherapy based on artificial intelligence algorithm. In this study, 100 patients with cervical squamous cell carcinoma with local recurrence and distant metastasis who underwent concurrent chemoradiotherapy were collected as the research subjects, and all underwent MRI multisequence imaging scans. At the same time, according to the evaluation criteria of solid tumor efficacy, patients with complete remission were classified into the effective group, and patients with partial remission, progressive disease, and stable disease were classified into the ineffective group. In addition, an image segmentation algorithm based on Balloon Snake model was proposed for MRI image processing, and simulation experiments were carried out. The results showed that the Dice coefficient of the proposed model segmentation of the reconstructed image was significantly higher than that of the level set model and the greedy algorithm, while the running time was the opposite (P < 0.05). The lesion volume (38.76 ± 5.34 cm3) in the effective group after treatment was significantly smaller than that in the noneffective group (46.33 ± 4.64 cm3), and the rate of lesion volume shrinkage (28.71%) was significantly larger than that in the noneffective group (12.49%) (P < 0.05). The relative apparent diffusion coefficient (rADC) value and rADC value change rate of the lesion after treatment in the effective group were significantly greater than those in the noneffective group (P < 0.05). In summary, the image segmentation and reconstruction algorithm based on Balloon Snake model can not only improve the quality of MRI images but also shorten the processing time and improve the diagnostic efficiency. The volume regression rate and rADC value change rate of cervical squamous cell carcinoma lesion can reflect the early efficacy of concurrent chemoradiotherapy for cervical squamous cell carcinoma and have predictive value.

Recurrent squamous cell carcinoma and a novel mutation in a patient with xeroderma pigmentosum: a case report

BackgroundXeroderma pigmentosum is an extremely serious genetic disorder defined by sensitivity to sunlight, resulting in sunburn and pigment changes. If patients are not completely protected from ultraviolet radiation, xeroderma pigmentosum is characterized by a greatly increased risk of sunlight-induced cutaneous neoplasms. There is no standard therapy for skin cancer of xeroderma pigmentosum. However, immune checkpoint inhibitors were reported to increase response rates and improve outcomes and life expectancy in patients with various cancers, including squamous cell carcinoma in xeroderma pigmentosum. In this paper, we report on a patient with xeroderma pigmentosum from a consanguineous family with recurrent facial chemotherapy-resistant squamous cell carcinoma lesions treated successfully with an anti-programmed cell death protein 1 monoclonal antibody in both relapses.Case presentationA 7-year-old Turkish male was referred to our oncology department for recurring squamous cell carcinoma after local excision of the tumor over his nose. The lesion was a rapidly growing lesion, measuring 8 × 4 cm in size. Physical examination revealed that he also had hemorrhagic crusted plaques and nodules over both eyelids and upper lip, with multiple hypo- and hyperpigmented punctate lesions all over his body. After two more cycles of chemotherapy, progressive disease was noted, and a new lesion on the right eyelid caused blurred vision. Anti-programmed cell death protein 1 antibody treatment was planned with concomitant radiotherapy. He received nivolumab every 3 weeks for 4 months, improving his vision. No new lesions or active complaints have been observed in the current situation, and complete remission has been achieved. On the last admission, the patient was clinically diagnosed with xeroderma pigmentosum. Owing to the condition’s genetic heterogeneity, whole-exome sequencing was performed with Ion Proton next-generation sequencing platform, and the c.2250 + 1G>A splice site mutation of the XPC gene was detected in the homozygous state.ConclusionsThe clinical report emphasizes the importance of clinical awareness and crucial early diagnosis of xeroderma pigmentosum and presents a novel causative homozygous c.2250 + 1G>A splice site mutation. Our case proves that next-generation sequencing is an effective method for the rapid diagnosis and determination of xeroderma pigmentosum genetic etiology.

Therapeutic efficacy of “Omeprazole” in horses with equine gastric ulcer syndrome

Gastric ulcer syndrome most often appears in horses as erosions and ulcers of the squamous gastric mucosa. It is believed that gastric ulcers of various etiologies are determined by the amount of gastric acidity regulated by the secretion of hydrochloric acid (HCL). At the same time, the squamous portion of the stomach is the most sensitive to HCL. When ulcers appear, medical treatment is effective. This medicine includes gastric acid suppressor drugs like “Omeprazole”. The mechanism of action whose final stage is to inhibit HCL secretion at the cellular level. Today the importance of antisecretory therapy is well known in treating gastroesophageal reflux and peptic ulcer diseases in humans. However, the acid-suppressive effect of “Omeprazole” in horses with gastric ulcers requires further research. This study aimed to determine the therapeutic efficacy and acid-suppressive effect of the proton pump inhibitor “Omeprazole” in doses of 2 mg/kg and 4 mg/kg. For this purpose, n = 14 horses were selected for the research with the equine gastric squamous disease of various degrees. Gastric squamous portion were observed by gastroscopy procedure and presented with mild lesions in selected horses. Diagnosis of lesions and determination of therapeutic efficacy of the drug was carried out based on gastroscopy results. The drug was administered per os for 21 days. The intragastric pH value determined the acid-supressive effect of the drug. Collection of the samples was conducted on the 1st, 5th, 10th, and 21st day of the medical therapy. Before “Omeprazole” was administrated, the basal pH level was 3.45 ± 0.23. After the first dose of the “Omeprazole” was administered at 4 mg/kg the average pH value was 5.25 ± 0.34. At the same time, the “Omeprazole” at a dose of 2 mg/kg provides intragastric pH 4.41 ± 0.33. The therapeutic efficacy of “Omeprazole” is closely related to the intragastric pH of the horses. The “Omeprazole” at a dose of 4mg/kg is highly effective in treating squamous lesions grade 2, 3. However, the duration of therapy for 21 days may not be sufficient to achieve complete healing of the affected tissues. Administration of the “Omeprazole” at a dose of 2 mg/kg is effective in treating small or multifocal lesions and hyperemia of the squamous mucosa.

Inter- and intraobserver agreement in whole-slide digital ThinPrep samples of low-grade squamous lesions of the cervix uteri with known high-risk HPV status: A multicentric international study.

High-risk human papilloma virus (HR HPV) testing and liquid-based cytology are used for primary cervical screening. Digital cytology, based on whole-slide scanned samples, is a promising technique for teaching and diagnostic purposes. The aim of our study was to evaluate the interobserver and intraobserver variation in low-grade squamous lesions, HR HPV status bias, and the use of whole-slide scanned digital cervical cytology slides. Fifteen expert cytopathologists evaluated 71 digitalized ThinPrep slides (31 atypical squamous cells of undetermined significance [ASC-US], 21 negative for intraepithelial lesion or malignancy, and 19 low-grade squamous intraepithelial lesion cases). HR HPV data were accessible only in the second round. In interobserver analysis, Kendall's coefficient of concordance was 0.52 in the first round and 0.58 in the second round. Fleiss' kappa values were 0.29 in the first round and 0.31 in the second round. In the ASC-US category, Fleiss kappa increased from 0.19 to 0.22 in the second round and the increase was even higher expressed by Kendall's coefficient: from 0.42 to 0.52. In intraobserver analysis, personal scores were higher in the second round. The interobserver and intraobserver variability in low-grade squamous lesions was within fair agreement values in the present study, in line with previous works. The comparison of two rounds showed that expert cytopathologists are generally unbiased by the knowledge of HR HPV data, but that being informed of the HR HPV status leads to a better agreement. Stain quality and back discomfort were highlighted as factors affecting digital cytopathology use.

Clinicopathological characteristics of ocular surface squamous neoplasia: a 10-year review form a referral tertiary centre in Nigeria.

Ocular surface squamous neoplasia (OSSN) is a heterogeneous group of proliferative squamous lesions on the ocular surface with varying biologic behaviours. This study aims to report the clinical profile and pathological characteristics of cases of OSSN seen at a tertiary referral centre in North West Nigeria. A retrospective review of all cases of OSSN diagnosed over a 10-year period was done. OSSN accounted for 68 out of 91 ocular surface lesions affecting twice as many males as females and a peak incidence in the 30-39years age group. They frequently presented as higher-grade and higher-stage lesions with invasive squamous cell carcinoma being the most frequently diagnosed OSSN. They also frequently showed an association with HIV infection and a relatively long duration of symptoms before presentation. OSSN occurs in a relatively young age group in our environment. Certain clinical and epidemiological features appear to predict the occurrence of higher-grade lesions, and this may help in the clinical prediction of likely pathologic grade and/or biologic behaviour of these lesions.

Comparison of four assays for human papillomavirus detection in the anal canal

ObjectiveAnal cancer is preceded by high-risk human papillomavirus (HRHPV) infection, predominantly HPV16. No HPV assay is licenced for use in anal screening. We aimed to determine the sensitivity and specificity of four anal canal swab HPV assays to predict high-grade squamous epithelial lesions (HSIL). MethodsIn a cohort of Australian HIV-positive and negative gay and bisexual men, we compared the sensitivity and specificity of detection of 13 anal HRHPV genotypes by Linear Array (LA), Cobas 4800, EuroArray, and Anyplex II HPV28 (+ and ++ cut offs), compared their ability to predict prevalent anal HSIL, and compared anal canal HRHPV detection with HRHPV isolated from HSIL using laser capture microdissection (LCM). ResultsA total of 475 participants had baseline results available for all four assays (166, 35.0% HIV positive), and 169 participants had a diagnosis of cytological and/or histological HSIL. The HPV16 and any HRHPV detection were highest with Anyplex II HPV28 (+) (156, 32.8% 95% CI 28.6–37.2 and 359, 75.6%, 95% CI 71.5–79.4, respectively). For detection of concurrent HSIL and HPV16, the assay sensitivity was similar, ranging from 49.1%, 95% CI 41.4–56.9 (Anyplex II HPV28 ++) to 55.0%, 95% CI 47.2–62.7 (Anyplex II HPV28 +). For concurrent HSIL and any HRHPV detection, EuroArray was more specific than Anyplex II HPV28 (+) (45.9% 95% CI 40.2–51.7 vs 36.7%, 95% CI 31.3–42.4, p = 0.021) and had comparable specificity with Anyplex II HPV28 (++) (45.9% vs 47.2%, 95% CI 41.5–53.0, p = 0.75). All assays had high sensitivities for predicting HPV16 detected on LCM (92.5–97.5%). Anyplex II HPV28 and EuroArray were significantly more sensitive than LA for lesions caused by non-HPV16 HRHPV types on LCM. DiscussionAnyplex II HPV28 and EuroArray detected more non-16 HRHPV genotypes than LA. Increasing the Anyplex II HPV28 cutoff improved specificity without compromising sensitivity for detection of concurrent HSIL.

The expression of EGFR and clinicopathological parameters in oral squamous cell carcinoma

Background: Oral squamous cell carcinomas (OSCCs) are the most prevalent types of oral cancers. There are a variety of clinicopathological characteristics of these types. The epidermal growth factor receptor (EGFR) is an essential diagnostic, prognostic, and therapeutic marker of OSCCs. The purpose of the research is to analyze the immunohistochemical expression of EGFR in OSCCs and to correlate its expression with clinical measures. Materials and Methods: The present research included 44 histopathologically confirmed oral squamous cell carcinoma lesions. EGFR expression was determined by using immunohistochemical technique. The spss program version (20.0) was used to correlate the expressions EGFR with the clinical and histopathological parameters. Results: 25 (57%) were men, while 19 (43%) were women. Most lesions 14(31%) cases were on the buccal mucosa. The palate had the lowest incidence rate 3(6.8%) cases. The highest frequency of OSCC was in well-differentiated samples with 23 (52.3) cases. 15 (34.1%) instances had a poor EGFR score (+1), 17 (38.6%) cases had a moderate score (+2), and 8 (18.2%) had a high score (+3). Except for tumor grade (P = 0.001), none of the studied factors were correlated with EGFR expression. Conclusion: EGFR has prognostic value and is a good target for therapeutic applications in these tumors. More research needs to be done to see if EGFR levels can be used as a marker of prognosis and a predictor of tumor recurrence in other ways.

Absence of NOTCH1 mutation and presence of CDKN2A deletion predict progression of esophageal lesions.

Currently, surveillance for esophageal squamous cell carcinoma (ESCC) runs a risk of underestimation of early lesions which show absence of iodine staining, with no or only mild histologic changes. The development of molecular markers that indicate risk of progression is thus warranted. We performed whole-exome sequencing on biopsies from two sequential endoscopies of a single esophageal lesion and matching blood samples. There were 27 pairs of age-, gender-, pathologic stage-, and sampling interval-matched progressors and non-progressors identified in a prospective community-based ESCC screening trial. Putative molecular progression markers for ESCC were first evaluated by comparing somatic mutation, copy number alteration (CNA), and mutational signature information among progressors and non-progressors. These markers were then validated with another 24 pairs of matched progressors and non-progressors from the same population using gene alteration status identified by target sequencing and quantitative PCR. Progressors had more somatic mutation and CNA burden, as well as apolipoprotein B mRNA editing catalytic polypeptide-like and age-related signature weights compared with non-progressors. A gene score consisting of somatic NOTCH1 mutation and CDKN2A deletion is predictive of risk of progression in lesions which show absence of iodine staining under endoscopy but have no or only mild dysplasia. This gene score was also validated in an external cohort of matched progressors and non-progressors. Absence of NOTCH1 mutation and presence of CDKN2A deletion are markers of progression in squamous lesions of the esophagus. This gene score would be an ideal indicator for assisting the pathologist in the identification of high-risk individuals who could be potentially 'missed' or subject to a risk underestimation by histologic analysis, and might improve the performance of ESCC surveillance. © 2022 The Pathological Society of Great Britain and Ireland.

Artificial intelligence assisted cytological detection for early esophageal squamous epithelial lesions by using low-grade squamous intraepithelial lesion as diagnostic threshold.

Manual cytological diagnosis for early esophageal squamous cell carcinoma (early ESCC) and high-grade intraepithelial neoplasia (HGIN) is unsatisfactory. Herein, we have introduced an artificial intelligence (AI)-assisted cytological diagnosis for such lesions. Low-grade squamous intraepithelial lesion or worse was set as the diagnostic threshold for AI-assisted diagnosis. The performance of AI-assisted diagnosis was evaluated and compared to that of manual diagnosis. Feasibility in large-scale screening was also assessed. AI-assisted diagnosis for abnormal cells was superior to manual reading by presenting a higher efficiency for each slide (50.9 ± 0.8s vs 236.8 ± 3.9s, p=1.52 × 10-76 ) and a better interobserver agreement (93.27% [95% CI, 92.76%-93.74%] vs 65.29% [95% CI, 64.35%-66.22%], p=1.03 × 10-84 ). AI-assisted detection showed a higher diagnostic accuracy (96.89% [92.38%-98.57%] vs 72.54% [65.85%-78.35%], p=1.42 × 10-14 ), sensitivity (99.35% [95.92%-99.97%] vs 68.39% [60.36%-75.48%], p=7.11 × 10-15 ), and negative predictive value (NPV) (97.06% [82.95%-99.85%] vs 40.96% [30.46%-52.31%], p=1.42 × 10-14 ). Specificity and positive predictive value (PPV) were not significantly differed. AI-assisted diagnosis demonstrated a smaller proportion of participants of interest (3.73%, [79/2117] vs.12.84% [272/2117], p=1.59 × 10-58 ), a higher consistence between cytology and endoscopy (40.51% [32/79] vs. 12.13% [33/272], p=1.54 × 10- 8), specificity (97.74% [96.98%-98.32%] vs 88.52% [87.05%-89.84%], p=3.19 × 10-58 ), and PPV (40.51% [29.79%-52.15%] vs 12.13% [8.61%-16.75%], p=1.54 × 10-8 ) in community-based screening. Sensitivity and NPV were not significantly differed. AI-assisted diagnosis as primary screening significantly reduced average cost for detecting positive cases. Our study provides a novel cytological method for detecting and screening early ESCC and HGIN.

Detection of Human Papillomavirus in Squamous Lesions of the Conjunctiva Using RNA and DNA In-Situ Hybridization.

In-situ hybridization provides a convenient and reliable method to detect human papillomavirus (HPV) infection in formalin-fixed paraffin-embedded tissue. Cases of conjunctival papillomas, conjunctival intraepithelial neoplasia (CIN), conjunctival carcinoma in situ (cCIS), and invasive squamous cell carcinoma (SCC), in which low-risk (LR) and/or high-risk (HR) HPV types were evaluated by RNA or DNA in-situ hybridization, were retrospectively identified. LR HPV types were frequently detected in conjunctival papillomas (25/30, 83%), including 17/18 (94%) with RNA probes, compared to 8/12 (75%) with DNA probes. None of the CIN/cCIS or SCC cases were positive for LR HPV by either method. HR HPV was detected by RNA in-situ hybridization in 1/16 (6%) of CIN/cCIS cases and 2/4 (50%) of SCC cases, while DNA in-situ hybridization failed to detect HPV infection in any of the CIN/cCIS lesions. Reactive atypia and dysplasia observed in papillomas was generally associated with the detection of LR HPV types. Collectively, our findings indicate RNA in-situ hybridization may provide a high-sensitivity approach for identifying HPV infection in squamous lesions of the conjunctiva and facilitate the distinction between reactive atypia and true dysplasia. There was no clear association between HPV infection and atopy in papillomas or dysplastic lesions.

The Effectiveness of Topical 5-fluorouracil Treatment on Mouse Skin Squamous Cell Precancerous Lesions through Caspase-3 Expression

Skin cancer is a disease that develops in the epidermis of the skin and can be invasive, such as squamous cell carcinoma (SCC). Early detection of squamous cell precancerous can prevent these lesions from progressing to invasive SCC and increase the effectiveness of therapy. 5-fluorouracil (5-FU) is an antimetabolite compound as a pyrimidine DNA/RNA antagonist molecule that induces cell apoptosis. The main objective of this study was to evaluate the effectiveness of the topical 5-FU cream (Dharmais NCH) compared to imiquimod 5% on apoptosis through the expression of caspase-3 in precancerous squamous cells of mouse skin induced by 7,12-dimethylbenzen[a]-anthracene (DMBA)/croton oil treatment. This research assess three differences concentration of 5-FU include 1%, 2%, and 5% on 24 wild type mouse divided into 6 groups including positive control (with carcinogenesis but without treatment), negative control (without treatment; normal), carcinogenesis with treatment 5-FU cream (1%, 2%, and 5%) or 5% imiquimod cream. Two-stages carcinogenesis induced by DMBA and followed by croton oil. The expression of caspase-3 was analyzed using immunohistochemistry. Statistical analysis was performed by one-way ANOVA using SPSS version 23. The induction of two-stages of carcinogenesis (weeks 1 to 10) caused papilloma lesions on the skin of mouse. Furthermore, 5-FU treatment for 4 weeks (weeks 11 to 14) showed a decrease in the cumulative number of papillomas (p&lt;0.05) and immunohistochemical analysis showed caspase-3 expression on 5-FU treatments (1%, 2%, and 5%) was not significantly different from the imiquimod treatment (p&gt;0.05). The apoptotic effect of 5-FU treatment on precancerous skin squamous cell lesions in mouse was not significantly different from the standard treatment using imiquimod. This suggests that 5-FU treatment has potential as a future therapy in squamous cell precancerous skin lesions.Keywords: 5-fluorouracil, caspase-3, squamous cell precancerous, skin, topical treatment.