Research advances in signaling pathways related to the malignant progression of HSIL to invasive cervical cancer: A review.

The progression of high-grade squamous intraepithelial lesion (HSIL) to invasive cervical cancer (ICC) is a complex process involving persistent human papillomavirus (HPV) infection and changes in signal transduction regulation, energy and material metabolism, cell proliferation, autoimmune, and other biological process in vaginal microenvironment and immune microenviroment. Signaling pathways are a series of interacting molecules in cells that regulate various physiological functions of cells, such as growth, differentiation, metabolism, and death. In the progression of HSIL to ICC, abnormal activation or inhibition in signaling pathways plays an essensial role. This review presented some signaling pathways related to the malignant progression of HSIL to ICC, including p53, Rb, PI3K/AKT/mTOR, Wnt/ß-catenin, Notch, NF-κB, MAPK, TGF-ß, JAK-STAT, Hippo, and Hedgehog. The molecular mechanisms involved in the biological process of pathway regulation were also analyzed, in order to illustrate the molecular pathway of HSIL progression to ICC and provide references for the development of more effective prevention and treatment methods.

[[Artículo traducido]]Retrospective Study of Risk Markers for Developing High-Grade Anal Intraepithelial Neoplasm in Men Who Have Sex With Men Living With HIV.

High-grade anal intraepithelial squamous lesion is significantly prevalent among men who have sex with men and are infected with the human immunodeficiency virus. This condition-the precursor to anal cancer-significantly increases the risk of developing it. Conversely, low-grade anal intraepithelial squamous typically follow a benign course and usually regress spontaneously. MATERIALS AND METHODS: To describe a population of men who have sex with men living with human immunodeficiency virus followed in a specialized anal cancer screening unit we conducted an observational, retrospective, and single-center study was. RESULTS: Ninety-four patients were analyzed, with a mean age of 39 ± 9 years, and a 87% positivity rate for high-risk human papillomavirus (HR-HPV). At the initial visit, 47% presented with low-grade squamous intraepithelial lesions. The progression rate to high-grade squamous intraepithelial lesion was 37.2 per 100,000 patients/year. None of the patients developed anal cancer. Tobacco and alcohol consumption were associated with this progression. DISCUSSION: In this series, longer duration of HIV infection, tobacco and alcohol use and the presence of HR-HPV were significantly associated with the occurrence of high-grade intraepithelial lesions. A lower risk of progression was seen in patients with higher education. CONCLUSION: In men who have sex with men living with HIV, the association of factors such as smoking, alcohol, the presence of HR-HPV and an increased burden of human papillomavirus disease makes these patients more susceptible to develop high-grade anal squamous lesions.

Association Between Recurrence of High-grade Squamous Intraepithelial Lesions of the Uterine Cervix and p16, C-myc and PIK3CA Proteins-A Single-center Retrospective Study.

Cervical high-grade squamous intraepithelial lesions (HSIL) are one of the common types of cervical cancer precancerous changes, and HPV16/18 positivity is a risk factor for HSIL recurrence. By detecting the expression of relevant markers in the lesion tissue of recurrent patients, it is helpful for the diagnosis of HPV16/18 positivity and can provide a basis for disease recurrence risk assessment. Therefore, this study analyzed the relationship between p16, C-myc, PIK3CA proteins and HPV16/18 positivity in recurrent cervical HSIL patients. By examining the p16, C-myc, and PIK3CA proteins in the cervical lesion tissue of 180 HSIL recurrent patients who underwent examination in the hospital from January 2020 to December 2022, this study analyzed the relationship between p16, C-myc, and PIK3CA proteins and HPV16/18 positivity. PIK3CA expression detection found that the proportion of positive expression of p16, C-myc, and PIK3CA in HPV16/18 (+) patients was significantly higher than that in HPV16/18 (-), and the expression of HPV16/18 in HSIL patients was significantly positively correlated with p16, C-myc, and PIK3CA. Meanwhile, a prediction model F was constructed based on binary logistic regression analysis data with good fit, and through ROC curve analysis. It was found that p16, C-myc, PIK3CA, and logistic model F can effectively predict HPV16/18 (+), with model F having the best diagnostic performance.

The prevalence of HPV in Chongqing, China from 2017 to 2022: a retrospective cohort study.

BACKGROUND AND AIMS: Human papillomavirus (HPV) infection is widespread. The regional differences in infection rates and dominant HPV types are a significant aspect of the virus's epidemiological characteristics. In China, these differences are further influenced by the country's diverse ethnic composition, as well as varying economic and cultural conditions across regions. Additionally, factors such as population migration contribute to the exacerbation of these regional disparities in HPV infection rates. METHODS: We conducted an analysis of the current prevalence of HPV among 108,863 patients in Chongqing from 2017 to 2022, along with an investigation into the interaction between HPV and vaginal microbiota. Additionally, we explored the relationship between HPV clearance time and disease outcomes. RESULTS: Our findings revealed an overall HPV positive rate of 30.14% (32,813/108,863) in Chongqing, China. The top five HPV positive rates were as follows: HPV52 (7.78%), HPV16 (5.85%), HPV58 (4.41%), HPV53 (3.17%), and HPV39 (2.47%). The age-related trend of HPV infection exhibited a bimodal curve. Importantly, the positive rate of high-risk HPV (BV: 24.74%, AV: 24.38%, VVC: 18.19%, TV: 22.81%) was significantly higher than those in the control group (all P<0.05). Follow-up for 4 years, we observed an overall clearance rate of HPV at 92.20%, with a median clearance time of 13 (1-61) months. CONCLUSION: These findings hold significant implications for the Chinese government in evaluating the prevalence of HPV in the Chongqing region and formulating effective HPV prevention strategies. Moreover, these findings could contribute to the enhancement of public health initiatives related to HPV in the region.

Subgroup Analysis of TLR2, -3, -4 and -8 in Relation to the Severity of Clinical Manifestations of Cervical HPV Infection.

We present the findings of assessing the expression levels of extracellular TLR2 and TLR4 and intracellular TLR3 and TLR8 correlating with the severity of clinical manifestations of HPV infection. A total of 199 women took part in a single-center prospective comparative research study on TLR2, TLR3, TLR4 and TLR8 expression in HPV-related cervical lesions. TLRs' mRNA expression was analyzed using real-time reverse transcription polymerase chain reaction (RT-PCR). Our results indicate the potential significance of TLR3, TLR4 and TLR8 in responding to HPV infection and its progression to SILs and CC, highlighting the importance of HPV polyinfection in relation to TLR4 and TLR8.

Therapeutic effects of focused ultrasound on vulvar squamous intraepithelial lesions in rat.

OBJECTIVE: In this study, we established a Sprague-Dawley rat model of vulvar squamous intraepithelial lesions and investigated the impact of focused ultrasound on the expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and mutant type p53 (mtp53) in the vulvar skin of rats with low-grade squamous intraepithelial lesions (LSIL). MATERIALS AND METHODS: The vulvar skin of 60 rats was treated with dimethylbenzanthracene (DMBA) and mechanical irritation three times a week for 14 weeks. Rats with LSIL were randomly allocated into the experimental group or the control group. The experimental group was treated with focused ultrasound, while the control group received sham treatment. RESULTS: After 14 weeks treatment of DMBA combined with mechanical irritation, LSIL were observed in 44 (73.33%) rats, and high-grade squamous intraepithelial lesions (HSIL) were observed in 14 (23.33%) rats. 90.91% (20/22) of rats showed normal pathology and 9.09% (2/22) of rats exhibited LSIL in the experimental group at four weeks after focused ultrasound treatment. 22.73% (5/22) of rats exhibited LSIL, 77.27% (17/22) of rats progressed to HSIL in the control group. Compared with the control-group rats, the levels of HIF-1α, VEGF and mtp53 were significantly decreased in experimental-group rats (p < 0.05). CONCLUSIONS: These results indicate that DMBA combined with mechanical irritation can induce vulvar squamous intraepithelial lesion in SD rats. Focused ultrasound can treat LSIL safely and effectively, prevent the progression of vulvar lesions, and improve the microenvironment of vulvar tissues by decreasing the localized expression of HIF-1α, VEGF, and mtp53 in rats.

Safety and Immunogenicity of the Nonavalent Human Papillomavirus Vaccine in Women Living with HIV.

BACKGROUND: The objectives were to evaluate the safety and immunogenicity of the nonavalent human papillomavirus (nHPV) vaccine in adult Spanish women living with HIV (WLHIV); the prevalence of anal and cervical dysplasia and nHPV vaccine genotypes in the anus and cervix; and risk factors for high-risk HPV (HR-HPV) infection in anal mucosa. METHODS: In this single-center, open-arm, non-randomized clinical trial, the nHPV vaccine was administered at 0, 2, and 6 months to WLHIV enrolled between February 2020 and November 2023, measuring vaccine antibody titers pre-vaccination and at 2, 6, and 7 months after the first dose. Cervical and anal cytology and HPV PCR genotyping studies were performed. Women with abnormal cytology and/or anal or cervical HPV infection at baseline underwent high-resolution anoscopy and/or colposcopy. RESULTS: A total of 122 participants were included with mean age of 49.6 years: 52.5% smoked; 10.7% had anal-genital condylomatosis; 38.5% were infected by HR-HPV in the anus and 25.4% in the cervix, most frequently HPV 16; 19.1% had anal intraepithelial neoplasia 1-(AIN1); and 3.1% had cervical intraepithelial neoplasia 1 and 2 (CIN1/CIN2). Vaccine administration did not modify viral-immunological status (CD4 [809 ± 226.8 cells/uL vs. 792.35 ± 349.95; p = 0.357]) or plasma HIV load (3.38 ± 4.41 vs. 1.62 ± 2.55 cop/uL [log]; p = 0.125). Anti-HPV antibodies ([IQR: 0-0] vs. 7.63 nm [IQR: 3.46-19.7]; p = 0.0001) and seroconversion rate (8.2% vs. 96.7% [p = 0.0001]) were increased at 7 versus 0 months. There were no severe vaccine-related adverse reactions; injection-site pain was reported by around half of the participants. HR-HPV infection in the anus was solely associated with a concomitant cervix infection (HR 5.027; 95% CI: 1.009-25.042). CONCLUSIONS: nHPV vaccine in adult WLHIV is immunogenic and safe.

Distribution and diagnostic value of single and multiple high-risk HPV infections in detection of cervical intraepithelial neoplasia: A retrospective multicenter study in China.

The risk associated with single and multiple human papillomavirus (HPV) infections in cervical intraepithelial neoplasia (CIN) remains uncertain. This study aims to explore the distribution and diagnostic significance of the number of high-risk HPV (hr-HPV) infections in detecting CIN, addressing a crucial gap in our understanding. This comprehensive multicenter, retrospective study meticulously analyzed the distribution of single and multiple hr-HPV, the risk of CIN2+, the relationship with CIN, and the impact on the diagnostic performance of colposcopy using demographic information, clinical histories, and tissue samples. The composition of a single infection was predominantly HPV16, 52, 58, 18, and 51, while HPV16 and 33 were identified as the primary causes of CIN2+. The primary instances of dual infection were mainly observed in combinations such as HPV16/18, HPV16/52, and HPV16/58, while HPV16/33 was identified as the primary cause of CIN2+. The incidence of hr-HPV infections shows a dose-response relationship with the risk of CIN (p for trend <0.001). Compared to single hr-HPV, multiple hr-HPV infections were associated with increased risks of CIN1 (1.44, 95% confidence interval [CI]: 1.20-1.72), CIN2 (1.70, 95% CI: 1.38-2.09), and CIN3 (1.08, 95% CI: 0.86-1.37). The colposcopy-based specificity of single hr-HPV (93.4, 95% CI: 92.4-94.4) and multiple hr-HPV (92.9, 95% CI: 90.8-94.6) was significantly lower than negative (97.9, 95% CI: 97.0-98.5) in detecting high-grade squamous intraepithelial lesion or worse (HSIL+). However, the sensitivity of single hr-HPV (73.5, 95% CI: 70.8-76.0) and multiple hr-HPV (71.8, 95% CI: 67.0-76.2) was higher than negative (62.0, 95% CI: 51.0-71.9) in detecting HSIL+. We found that multiple hr-HPV infections increase the risk of developing CIN lesions compared to a single infection. Colposcopy for HSIL+ detection showed high sensitivity and low specificity for hr-HPV infection. Apart from HPV16, this study also found that HPV33 is a major pathogenic genotype.

Retrospective Study of Risk Markers for Developing High-Grade Anal Intraepithelial Neoplasm in Men Who Have Sex With Men Living With HIV. / Estudio retrospectivo que evalúa marcadores de riesgo de desarrollar lesión escamosa intraepitelial anal de alto grado en hombres que tiene sexo con hombres y viven con el virus de inmunodeficiencia humana.

BACKGROUND: High-grade anal intraepithelial squamous lesion is significantly prevalent among men who have sex with men and are infected with the human immunodeficiency virus (HIV). This condition-the precursor to anal cancer-significantly increases the risk of developing it. Conversely, low-grade anal intraepithelial squamous typically follow a benign course and usually regress spontaneously. MATERIALS AND METHODS: To describe a population of men who have sex with men living with HIV followed in a specialized anal cancer screening unit we conducted an observational, retrospective, and single-center study. RESULTS: Ninety-four patients were analyzed, with a mean age of 39±9 years, and a 87% positivity rate for high-risk human papillomavirus (HR-HPV). At the initial visit, 47% presented with low-grade squamous intraepithelial lesions. The progression rate to high-grade squamous intraepithelial lesion was 37.2 per 100,000 patients/year. None of the patients developed anal cancer. Tobacco and alcohol consumption were associated with this progression. DISCUSSION: In this series, longer duration of HIV infection, tobacco and alcohol use and the presence of HR-HPV were significantly associated with the occurrence of high-grade intraepithelial lesions. A lower risk of progression was seen in patients with higher education. CONCLUSION: In men who have sex with men living with HIV, the association of factors such as smoking, alcohol, the presence of HR-HPV and an increased burden of human papillomavirus disease makes these patients more susceptible to develop high-grade anal squamous lesions.

Copy Number Profiling Implicates Thin High-Grade Squamous Intraepithelial Lesions as a True Precursor of Cervical Human Papillomavirus-Induced Squamous Cell Cancer.

Full-thickness high-grade squamous intraepithelial lesions (HSIL) are precursors of invasive cervical squamous cell carcinoma (SCC). The World Health Organization and Lower Anogenital Squamous Terminology Standardization Project for human papilloma virus (HPV)-associated lesions divide full-thickness HSIL of the cervix into thin HSIL with thickness of 1 to 9 cell layers and the typical full-thickness HSIL of >10 cell layers. Although HPV oncogene transcripts and p16ink4a overexpression, as markers of transforming HPV infection, are detectable in thin HSIL, the biological significance of thin HSIL in cervical carcinogenesis remains poorly understood. To further characterize thin HSIL, we performed a comparative study of chromosomal copy number variations (CNV), an analysis of dysregulated genes present in the segments with CNV, and a generalized genetic complexity calculation for 31 thin HSIL, 31 thick HSIL, 24 microinvasive SCC (pT1a SCC), and 22 highly invasive SCC samples. Thin HSIL share various CNV and specific dysregulated gene pathways with thick HSIL and invasive SCC. Thin HSIL exhibited an average CNV of 11.6% compared with 14.1% for thick HSIL, 15.5% for pT1a SCC, and 26.6% for highly invasive SCC. The CNV included gains at 1q and 3q (40% and 43%, respectively), partial loss of 3p, and loss of chromosomes 11 (18%), 16 (50%), 20 (35%), and 22 (40%). Pathways affected solely in thin HSIL were those enhancing immune evasion and primarily involved the (interleukin) IL6, IL21, and IL23 genes. ILs are transiently upregulated in response to infection and play a crucial role in mounting antitumor T-cell activity. Deregulation reflects an attempt by the HPV to evade the initial immune response of the host. The primary pathways shared by thick HSIL and invasive SCC were interactions between lymphoid and nonlymphoid cells, NOTCH2 signaling, tight junction interactions (primarily of the claudin family), and FGR2 alternative splicing. Our results show that thin HSIL carry similar genetic changes as thick HSIL and SCC, indicating that thin HSIL are true precursor lesions that can progress to thick HSIL and SCC.

HPV DNA status and clinical history of patients are supplements for accurate reporting of the cytological Pap smear.

The present study was aimed at showing the importance of HPV DNA status and the clinical history of the patients required by the cytologist for accurate reporting. A total of 1250 symptomatic women who attended the gynaecology outpatient department of the Mahavir Cancer Sansthan and Nalanda Medical College, Patna, for pap smear examinations were screened and recruited for the study. Due to highly clinical symptoms out of the negative with inflammatory smears reported, one hundred and ten patients were randomly advised for biopsy and HPV 16/18 DNA analysis by a gynaecologist to correlate negative smears included in the study. Pap smear reports revealed that 1178 (94.24%) were negative for intraepithelial lesions (NILM) with inflammatory smears, 23 (1.84%) smears showed low-grade squamous intraepithelial lesions (LSIL), 12 (0.96%) smears showed high-grade squamous intraepithelial lesions, and 37 (2.96%) smears showed an atypical squamous cell of undetermined significance (ASC-US). A biopsy of 110 out of 1178 (NILM) patients revealed that 15 (13.63%) women had cervical cancer, 29 women had CIN I, 17 women had CIN II + CIN III, 35 women had benign cervical changes, and 14 women had haemorrhages. On the other hand, HPV 16/18 DNA was detected as positive in 87 out of 110. The high positivity of HPV in biopsied cases where frank cervical cancer and at-risk cancer were also observed in the negative smear-screened patients reveals that the HPV status and clinical history of the patients will be quite helpful to the cytologist for accurate reporting, and suggests that a negative HPV DNA result may be a stronger predictor of cervical cancer risk than a negative Pap test.

Clinical application of endoscopic submucosal dissection for superficially invasive squamous cell carcinoma/high-grade squamous intraepithelial lesion involving the canal anal.

BACKGROUND: Superficially invasive squamous cell carcinoma (SISCC) and high-grade squamous intraepithelial lesions (HSIL) involving the anal canal are rare, and their surgical management involves local excision. Endoscopic submucosal dissection (ESD) has recently emerged as a promising treatment. This study aimed to evaluate the feasibility and safety of ESD for SISCC and HSIL in the anal canal. METHODS: All patients diagnosed with SISCC or HSIL in the anal canal who underwent ESD between November 2018 and May 2023 were included. Patient age, sex, pathology, human immunodeficiency virus (HIV) status, human papillomavirus (HPV) status, T stage, en bloc rate, and R0 resection rate were analyzed. RESULTS: Ten patients, including two men and eight women, with a median age of 61 (51-68) years were enrolled. All patients were HIV-negative, but five (50%) were HPV-positive. Pathological examination showed tumor stage of two patients as T2, one as T0 of SISCC, and seven as Tis of HSIL. The median specimen and tumor sizes were 24 (6-65) mm and 18 (6-55) mm, respectively. The en bloc and R0 resection rates were 100% and 80%, respectively. No severe complications occurred and no recurrence was observed at the follow-up (median follow-up period, 9 (1-35) months). CONCLUSIONS: ESD is a reliable and minimally invasive procedure that enables more individualized treatment options for specific groups. As we were limited by the length of the observation period, the long-term performance of ESD for SISCC and HSIL involving the anal canal requires further investigation.

HiPorfin photodynamic therapy for vaginal high-grade squamous intraepithelial lesion.

PURPOSE: We aimed to evaluate the efficacy and safety of HiPorfin-photodynamic therapy (PDT) in women with vaginal high-grade squamous intraepithelial Lesion (HSIL). METHODS: Retrospective analysis of eighteen patients with vaginal HSIL received HiPorfin-PDT between June 2019 and May 2023. Illumination with a 630-nm laser light was applied to the lesions 48-72 h after intravenous injection of 2 mg/kg HiPorfin®. The light dose to the lesions was 150 J/cm2. RESULTS: The mean age of the 18 patients was 45.8 years (range, 24 to 63). The complete response (CR) rate was 66.7% (12/18), 83.3% (15/18) and 83.3% (15/18) at 3, 6 and 12 months after PDT, respectively. Patients who achieved CR showed no signs of recurrence during long-term follow-up. There were three cases of persistent disease showing partial response (PR) and the lesion area was significantly reduced more than 50%. One patient with persistent disease then underwent thermocoagulation one time and subsequently showed no evidence of HSIL. Pre-treatment, 100% (18/18) patients were high-risk human papilloma virus (HR-HPV)-positive. HPV eradication rate was 16.7% (3/18), 22.2% (4/18) and 44.4% (8/18) after PDT at 3, 6 and 12 months, respectively. Before treatment, liquid-based cytology test ≥ atypical squamous cells of undetermined significance (ASCUS) was 94.4% (17/18). Negative conversion ratio of cytology was 47.1% (8/17), 52.9% (9/17) and 76.5% (13/17) at 3, 6 and 12 months, respectively. There were no serious adverse effects during and after PDT. CONCLUSIONS: HiPorfin-PDT may be an effective alternative treatment for vaginal HSIL for organ-saving and sexual function protection.

Comparative study of photodynamic therapy (PDT) of cervical low-grade squamous intraepithelial lesion (LSIL).

BACKGROUND: Prevention of high-risk HPV (HR-HPV) infection and effective medical intervention of persistent HPV infection and precancerous lesions are critical for the prevention of cervical cancer. AIMS: The aim of this retrospective comparative study was to evaluate the outcomes of ALA PDT and observation only in the management of low-grade squamous intraepithelial lesions (LSIL). METHODS: In PDT Group (n = 138), ALA PDT was applied to patients with colposcopic biopsy confirmed cervical LSIL accompanied with HR-HPV infection longer than 1 year or HPV 16/18 subtype infection. Cervical LSIL only patients received 3 times of ALA PDT and those with concurrent cervical canal or vaginal lesions received 6 times ALA PDT. Control Group (n = 69) received observation only. Colposcopy, TCT and HPV typing were performed before and after treatment. Patients were followed up for up to two years. RESULT: The observation group showed 26.1%, 34.8% and 53.6% HR-HPV negative conversion at 3-6, 12 and 24 months, respectively. LSIL regression rate of the observation group was 33.33%, 36.23% and 65.22% at 3-6, 12 and 24 months, respectively. There was 62.32%, 80.56% and 89.22% patients achieved HPV clearance at 3-6, 12 and 24 months after PDT treatment, respectively. The LSIL remission rate was 89.86%, 94.40% and 96.08% at 3-6, 12 and 24 months after ALA PDT, respectively. The abnormal TCT (≧ ASCUS) was reduced from 92% to 10.1%, 4.6% and 3.9% at 3-6, 12 and 24 months after ALA PDT, respectively. The patient age was not a factor affecting the clearance of HPV infection and the LSIL regression rate of PDT treatment. CONCLUSIONS: This study demonstrates that the application of multiple ALA PDT treatments has added value in achieving both short-term and long-term HPV and lesion clearance.

Performance of P16INK4a immunocytochemical stain in facilitating cytology interpretation of HSIL for HPV-positive women aged 50 and above.

Background: Few articles have focused on the cytological misinterpretation of high-grade squamous intraepithelial lesion (HSIL). Due to estrogen deficiency, cervical epithelial cells in postmenopausal women tend to show atrophic change that looks like HSIL on Papanicolaou-stained cytology slides, resulting in a higher rate of cytological misinterpretation. P16INK4a immunocytochemical staining (P16 cytology) can effectively differentiate diseased cells from normal atrophic ones with less dependence on cell morphology. Objective: To evaluate the role of P16 cytology in differentiating cytology HSIL from benign atrophy in women aged 50 years and above. Methods: Included in this analysis were women in a cervical cancer screening project conducted in central China who tested positive for high-risk human papillomavirus (hr-HPV) and returned back for triage with complete data of primary HPV testing, liquid-based cytology (LBC) analysis, P16 immuno-stained cytology interpretation, and pathology diagnosis. The included patients were grouped by age: ≥50 (1,127 cases) and <50 years (1,430 cases). The accuracy of LBC and P16 cytology in the detection of pathology ≥HSIL was compared between the two groups, and the role of P16 immuno-stain in differentiating benign cervical lesions from cytology ≥HSIL was further analyzed. Results: One hundred sixty-seven women (14.8%; 167/1,127) in the ≥50 group and 255 (17.8%, 255/1,430) in the <50 group were pathologically diagnosed as HSIL (Path-HSIL). LBC [≥Atypical Squamous Cell Of Undetermined Significance (ASCUS)] and P16 cytology (positive) respectively detected 63.9% (163/255) and 90.2% (230/255) of the Path-≥HSIL cases in the <50 group and 74.3% (124/167) and 93.4% (124/167) of the Path-≥HSIL cases in the ≥50 group. LBC matched with pathology in 105 (41.2%) of the 255 Path-≥HSIL cases in the <50 group and 93 (55.7%) of the 167 Path-≥HSIL cases in the ≥50 group. There were five in the <50 group and 14 in the ≥50 group that were Path-≤LSIL cases, which were interpreted by LBC as HSIL, but negative in P16 cytology. Conclusion: P16 cytology facilitates differentiation of Path-≤LSIL from LBC-≥HSIL for women 50 years of age and above. It can be used in the lower-resource areas, where qualified cytologists are insufficient, as the secondary screening test for women aged ≥50 to avoid unnecessary biopsies and misinterpretation of LBC primary or secondary screening.

Clinical evaluation of an artificial intelligence-assisted cytological system among screening strategies for a cervical cancer high-risk population.

BACKGROUND: Primary cervical cancer screening and treating precancerous lesions are effective ways to prevent cervical cancer. However, the coverage rates of human papillomavirus (HPV) vaccines and routine screening are low in most developing countries and even some developed countries. This study aimed to explore the benefit of an artificial intelligence-assisted cytology (AI) system in a screening program for a cervical cancer high-risk population in China. METHODS: A total of 1231 liquid-based cytology (LBC) slides from women who underwent colposcopy at the Chinese PLA General Hospital from 2018 to 2020 were collected. All women had received a histological diagnosis based on the results of colposcopy and biopsy. The sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), false-positive rate (FPR), false-negative rate (FNR), overall accuracy (OA), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and Youden index (YI) of the AI, LBC, HPV, LBC + HPV, AI + LBC, AI + HPV and HPV Seq LBC screening strategies at low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) thresholds were calculated to assess their effectiveness. Receiver operating characteristic (ROC) curve analysis was conducted to assess the diagnostic values of the different screening strategies. RESULTS: The Se and Sp of the primary AI-alone strategy at the LSIL and HSIL thresholds were superior to those of the LBC + HPV cotesting strategy. Among the screening strategies, the YIs of the AI strategy at the LSIL + threshold and HSIL + threshold were the highest. At the HSIL + threshold, the AI strategy achieved the best result, with an AUC value of 0.621 (95% CI, 0.587-0.654), whereas HPV testing achieved the worst result, with an AUC value of 0.521 (95% CI, 0.484-0.559). Similarly, at the LSIL + threshold, the LBC-based strategy achieved the best result, with an AUC of 0.637 (95% CI, 0.606-0.668), whereas HPV testing achieved the worst result, with an AUC of 0.524 (95% CI, 0.491-0.557). Moreover, the AUCs of the AI and LBC strategies at this threshold were similar (0.631 and 0.637, respectively). CONCLUSIONS: These results confirmed that AI-only screening was the most authoritative method for diagnosing HSILs and LSILs, improving the accuracy of colposcopy diagnosis, and was more beneficial for patients than traditional LBC + HPV cotesting.

Peripheral blood immune cell parameters in patients with high-grade squamous intraepithelial lesion (HSIL) and cervical cancer and their clinical value: a retrospective study.

Objective: The objective of this study was to delineate the profile of peripheral blood lymphocytic indices in patients afflicted with high-grade squamous intraepithelial lesions (HSIL) and cervical neoplasms, and to elucidate the correlation of these hematologic markers with the clinicopathological spectra in individuals diagnosed with cervical carcinoma. Methods: We adopted a retrospective case-control modality for this investigation. An aggregate of 39 HSIL patients and 42 cervical carcinoma patients, who were treated in our facility from July 2020 to September 2023, were meticulously selected. Each case of cervical malignancy was confirmed through rigorous histopathological scrutiny. Concomitantly, 31 healthy female individuals, who underwent prophylactic health evaluations during the corresponding timeframe, were enlisted as the baseline control group. We systematically gathered and analyzed clinical demographics, as well as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), from peripheral blood samples. Pearson's correlation coefficient was deployed to dissect the interrelation between peripheral NLR and PLR concentrations and the clinicopathological features in the cervical cancer group. Results: Inter-group comparative analysis unveiled statistically substantial variances in the PLR and NLR values among the tripartite clusters (F = 36.941, 14.998, P < 0.001, respectively). Although discrepancy in NLR (P = 0.061) and PLR (P = 0.759) measures between the groups of cervical carcinoma and HSIL was not statistically appreciable, these indices were markedly elevated in the cervical carcinoma faction as juxtaposed with the normative control group (t = 5.094, 5.927; P < 0.001 for both parameters). A discernible gradation in peripheral blood PLR and NLR concentrations was noted when stratified by clinical stage and the profundity of myometrial invasion in cervical cancer subjects (P < 0.001). The correlation matrix demonstrated a positive liaison between peripheral blood PLR and the clinical gradation, as well as the invasiveness of the neoplastic cells into the muscularis propria (P < 0.05); a similar trend was observed with the NLR values (P < 0.05). Conclusion: Augmented NLR and PLR levels in peripheral blood specimens are indicative of HSIL and cervical malignancy. These hematological parameters exhibit a pronounced interconnection with clinical staging and muscular wall penetration depth, serving as potential discriminative biomarkers for the diagnosis and prognosis of cervical cancer.

Preferred labels and language to discuss low-risk lesions that may be cancer precursors: A review.

OBJECTIVES: Patients diagnosed with low-risk lesions are confused about whether they have cancer, and experience similar anxiety to those with invasive cancer, which affects quality of life. Current labels for low-risk lesions were chosen by clinicians and lack meaning to patients. METHODS: We reviewed published research on preferred labels and language for low-risk lesions, and the rationale for those preferences. RESULTS: Of 6569 titles screened, we included 13 studies. Among healthy adults with cervix or prostate lesions, use of the term "cancer" rather than "nodule" or "lesion" resulted in greater anxiety, higher perceived disease severity, and selection of more invasive treatment. Physicians asked about removing "carcinoma" from thyroid lesion labels to reduce patient anxiety and discourage over-treatment did not support this change, instead preferring a term that included "neoplasm". CONCLUSIONS: This review revealed a startling paucity of research on preferences for low-risk lesion labels and language, and associated rationale. Future research is needed to understand how to improve communication about low-risk lesions. PRACTICE IMPLICATIONS: To reduce anxiety and improve the overall well-being of patients, it is crucial to gain a deeper understanding of how to improve patient-provider conversations regarding screen-detected lesions with a low risk of developing into invasive cancer.

Laminin receptor 1 expression in premalignant and malignant squamous lesions of the cervix.

Laminin receptor 1 (LAMR) may have a role in the progression of premalignant squamous epithelial lesions to cervical cancer. Therefore, we aimed to investigate the expression of laminin receptor 1 (LAMR) in normal, premalignant, and malignant tissues of the uterine cervix. Paraffin blocks of 129 specimens with the diagnoses of normal cervical tissue (n = 33), cervical intraepithelial neoplasia (CIN) 1 (n = 30), CIN 2 (n = 14), CIN 3 (n = 28), and squamous cell carcinoma (n = 24) were immunohistochemically stained with LAMR antibody and its expression percentage, pattern, and intensity in these tissues were assessed. Compared to the other groups, the nonstaining with LAMR was highest in low grade squamous intraepithelial lesion (LSIL) (p < 0.0001). LAMR expression, which was positive in less than 50% of cells with weak staining, increased significantly between normal cervical epithelium and high-grade squamous intraepithelial lesion (HSIL) or invasive carcinoma, as well as between LSIL and HSIL (p < 0.0001). Between LSIL and invasive carcinoma, a significant increment was also observed for weak staining in less than 50% of cells (p < 0.001). LAMR expression, which was positive in more than 50% of cells with strong staining, was significantly higher in normal cervical tissue compared to the other groups (p < 0.0001). Disease progression related gradual increment of LAMR expression from normal cervical epithelium or LSIL towards HSIL or cervical cancer reveals that LAMR may play an important role in the transition from premalignant to malignant state in cervical lesions.

The efficacy and safety of local 5-aminolevulinic acid-based photodynamic therapy in the treatment of cervical high-grade squamous intraepithelial lesion: a single center retrospective observational study.

Background: Typical treatments for cervical high-grade squamous intraepithelial lesion (HSIL) are invasive procedures. However, these procedures often come with several severe side effects, despite their positive effects on cervical HSIL. 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a non-invasive treatment that has been successfully used to treat cervical low-grade squamous intraepithelial lesion (LSIL). In this study, we aimed to further investigate the clinical efficacy and safety of ALA-PDT in the treatment of patients with cervical HSIL. Methods: A total of 40 patients aged 20 - 41 years with cervical HSIL and high-risk Human Papilloma Virus (HR-HPV) infections were enrolled in this retrospective study from January 2019 to December 2022. Patients were treated with six times of ALA-PDT at intervals of 7-14 days. Three months after the treatment, the efficacy was evaluated through HPV genotyping and cervical cytology examination. If the cytological result was worse than ASC -US, the patient underwent colposcopy-directed biopsy immediately. Otherwise, patients would receive rigorous follow-up observation. Results: Three months after receiving ALA-PDT treatment, 65% (26/40) of cervical HSIL patients at our center showed complete regression (cytological result: normal; HR-HPV: negative). This rate increased to 82.5% (33/40) at the 12-month follow-up. None of the patients experienced disease progression after ALA-PDT therapy. The risk of persistent HR-HPV infection was 32.5% (13/40) at the 3-month follow-up after ALA-PDT. Multivariate analyses identified cervical canal involvement as an independent risk factor for persistent HR-HPV infection at the 3-month follow-up after ALA-PDT treatment. During the treatment of the 40 patients with ALA-PDT, there were no reports of severe adverse reactions. Only a limited number of patients experienced slight discomfort symptoms. Conclusion: ALA-PDT is safe and effective noninvasive therapy for patients with cervical HSIL and HR-HPV infections. It is particularly suitable for young women, who have been confirmed with cervical HSIL and have demand for fertility protection. Three months after ALA-PDT treatment, if a patient still has either ASC-US cervical cytological result and/or HR-HPV infection, rigorous observation is considered safe for her. Cervical canal involvement is an independent risk factor for persistent HR-HPV infection at the 3-month follow-up after ALA-PDT treatment.