BACKGROUND: To investigate the causal relationship between human papillomavirus (HPV) and lung cancer, we conducted a study using the two-sample Mendelian randomization (TSMR).
METHODS: Data from genome-wide association studies (GWAS) were analyzed with HPV E7 Type 16 and HPV E7 Type 18 as exposure factors. The outcome variables included lung cancer, small cell lung cancer, adenocarcinoma and squamous cell lung cancer. Causality was estimated using inverse variance weighted (IVW), MR-Egger and weighted median methods. Heterogeneity testing, sensitivity analysis, and multiple validity analysis were also performed..
RESULTS: The results showed that HPV E7 Type 16 infection was associated with a higher risk of squamous cell lung cancer (OR = 7.69; 95% CI:1.98-29.85; p = 0.0149). HPV E7 Type 18 infection significantly increased the risk of lung adenocarcinoma (OR = 0.71; 95% CI: 0.38-1.31; p = 0.0079) and lung cancer (OR = 7.69; 95% CI:1.98-29.85; p = 0.0292). No significant causal relationship was found between HPV E7 Type 16 and lung adenocarcinoma, lung cancer, or small cell lung carcinoma, and between HPV E7 Type 18 and squamous cell lung cancer or small cell lung carcinoma.
CONCLUSIONS: This study has revealed a causal relationship between HPV and lung cancers. Our findings provide valuable insights for further mechanistic and clinical studies on HPV-mediated cancer.

UNASSIGNED: This study aimed to investigate the feasibility, efficacy, and safety of focused ultrasound (FUS) for the treatment of vulvar low-grade squamous intraepithelial lesions (VLSIL) with persistent symptoms.
UNASSIGNED: This retrospective analysis included 24 VLSIL patients who underwent FUS treatment. At each follow-up visit, the clinical response was assessed including changes in symptoms and signs. In addition, the histological response was assessed based on the vulvar biopsy results of the 3rd follow-up. Clinical and histological response were assessed to elucidate the efficacy.
UNASSIGNED: A total of 22 patients completed follow-up and post-treatment pathological biopsies. After treatment, the clinical scores of itching decreased from 2.55 ± 0.51 to 0.77 ± 0.81 (p < 0.05). Furthermore, the clinical response rate and histological response rate were 86.4% and 81.8%, respectively. Only two cured patients indicated recurrence in the 3rd and 4th year during the follow-up period and achieved cure after re-treatment. In terms of adverse effects, only one patient developed ulcers after treatment, which healed after symptomatic anti-inflammatory treatment without scarring, and no other treatment complications were found in any patients. None of the patients developed a malignant transformation during the follow-up period.
UNASSIGNED: This study revealed that FUS is feasible, effective, and safe for treating VLSIL patients with persistent symptoms, providing a new solution for the noninvasive treatment of symptomatic VLSIL.

OBJECTIVE: This study aims to analyze factors associated with positive surgical margins following cold knife conization (CKC) in patients with cervical high-grade squamous intraepithelial lesion (HSIL) and to develop a machine-learning-based risk prediction model.
METHODS: We conducted a retrospective analysis of 3,343 patients who underwent CKC for HSIL at our institution. Logistic regression was employed to examine the relationship between demographic and pathological characteristics and the occurrence of positive surgical margins. Various machine learning methods were then applied to construct and evaluate the performance of the risk prediction model.
RESULTS: The overall rate of positive surgical margins was 12.9%. Independent risk factors identified included glandular involvement (OR = 1.716, 95% CI: 1.345-2.189), transformation zone III (OR = 2.838, 95% CI: 2.258-3.568), HPV16/18 infection (OR = 2.863, 95% CI: 2.247-3.648), multiple HR-HPV infections (OR = 1.930, 95% CI: 1.537-2.425), TCT ≥ ASC-H (OR = 3.251, 95% CI: 2.584-4.091), and lesions covering ≥ 3 quadrants (OR = 3.264, 95% CI: 2.593-4.110). Logistic regression demonstrated the best prediction performance, with an accuracy of 74.7%, sensitivity of 76.7%, specificity of 74.4%, and AUC of 0.826.
CONCLUSIONS: Independent risk factors for positive margins after CKC include HPV16/18 infection, multiple HR-HPV infections, glandular involvement, extensive lesion coverage, high TCT grades, and involvement of transformation zone III. The logistic regression model provides a robust and clinically valuable tool for predicting the risk of positive margins, guiding clinical decisions and patient management post-CKC.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.

OBJECTIVE: To identify the risk factors of cervical high-grade squamous intraepithelial lesion(HSIL) complicated with occult cervical cancer and standardize the management of initial treatment for HSIL.
METHODS: The clinical data of patients who underwent total hysterectomy directly due to HSIL in the obstetrics and gynecology department of two tertiary hospitals and three secondary hospitals from 2018 to 2023 were collected. Their general characteristics, pathological parameters and survival status were analyzed. Logistic regression model was used to analyze the correlation between clinical parameters and postoperative pathological upgrading.
RESULTS: 1. Among the 314 patients with HSIL who underwent total hysterectomy directly, 73.2% were from primary hospitals. 2. 25 patients (7.9%) were pathologically upgraded to cervical cancer, all of which were early invasive cancer. 3. Up to now, there was no recurrence or death in the 25 patients with early-stage invasive cancer, and the median follow-up period was 21 months(range 2-59 months). 4. Glandular involvement(OR 3.968; 95%CI 1.244-12.662) and lesion range ≥ 3 quadrants (OR 6.527; 95% CI 1.78-23.931), HPV 16/18 infection (OR 5.382; 95%CI 1.947-14.872), TCT ≥ ASC-H (OR 4.719; 95%CI 1.892-11.766) were independent risk factors that affected the upgrading of postoperative pathology. 5. The area under the curve (AUC) calculated by the Logistic regression model was 0.840, indicating that the predictive value was good.
CONCLUSIONS: There is a risk of occult cervical cancer in patients with HSIL. Glandular involvement, Lesion range ≥ 3 quadrants, HPV 16/18 infection and TCT ≥ ASC-H are independent risk factors for HSIL combined with occult cervical cancer. The prognosis of biopsy-proved HSIL patients who underwent extrafascial hysterectomy and unexpected early invasive cancer was later identified on specimen may be good.

BACKGROUND: The cervix is the lower portion of the uterus, which connects this organ to the vagina through the endocervical canal.
OBJECTIVE: This study aimed to determine the histopathologic patterns and factors associated with cervical lesions at Jimma Medical Center from September 12, 2017, to September 12, 2019.
METHODS: A 2-year facility-based cross-sectional study was conducted from May 1 to June 30, 2020.
RESULTS: In this study, cervical cancer was the most common (71%) cause of cervical lesions. Squamous cell carcinoma was the most frequent cervical cancer diagnosed during the study, accounting for 96.4% of 331 cancerous cases, followed by adenocarcinoma (3.3%). High-grade squamous intraepithelial lesions were the most frequently diagnosed precancerous lesions, accounting for 68.4% of cases. Endocervical polyps were the most commonly diagnosed benign lesions, accounting for 59.3% of cases.
CONCLUSIONS: The maximum age distribution of cervical lesions was in the 41-50-year age range. Squamous cell carcinoma was the most frequent type of cervical cancer. High-grade squamous intraepithelial lesions were the most frequently diagnosed precancerous cervical lesions. The most common benign cervical lesions were endocervical polyps.
CONCLUSIONS: We recommend educating the community to improve health-seeking behavior and on possible preventive strategies for cervical cancer.

Demand for anal cancer screening is expected to rise following the recent publication of the Anal Cancer-HSIL Outcomes Research trial, which showed that treatment of high-grade squamous intraepithelial lesions significantly reduces the rate of progression to anal cancer. While screening for human papillomavirus-associated squamous lesions in the cervix is well established and effective, this is less true for other sites in the lower anogenital tract. Current anal cancer screening and prevention rely on high-resolution anoscopy with biopsies. This procedure has a steep learning curve for providers and may cause patient discomfort. Scattering-based light-sheet microscopy (sLSM) is a novel imaging modality with the potential to mitigate these challenges through real-time, microscopic visualization of disease-susceptible tissue. Here, we report a proof-of-principle study that establishes feasibility of dysplasia detection using an sLSM device. We imaged 110 anal biopsy specimens collected prospectively at our institution\'s dysplasia clinic (including 30 nondysplastic, 40 low-grade squamous intraepithelial lesion, and 40 high-grade squamous intraepithelial lesion specimens) and found that these optical images are highly interpretable and accurately recapitulate histopathologic features traditionally used for the diagnosis of human papillomavirus-associated squamous dysplasia. A reader study to assess diagnostic accuracy suggests that sLSM images are noninferior to hematoxylin and eosin images for the detection of anal dysplasia (sLSM accuracy = 0.87; hematoxylin and eosin accuracy = 0.80; P = .066). Given these results, we believe that sLSM technology holds great potential to enhance the efficacy of anal cancer screening by allowing accurate sampling of diagnostic tissue at the time of anoscopy. While the current imaging study was performed on ex vivo biopsy specimens, we are currently developing a handheld device for in vivo imaging that will provide immediate microscopic guidance to high-resolution anoscopy providers.

OBJECTIVE: The study aimed to compare the clinical efficacy and safety of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) and surgery in treating recurrent cervical high-grade squamous intraepithelial lesions (HSIL) after surgery due to precancerous lesions.
METHODS: A total of 41 patients with recurrent cervical HSIL after surgery for precancerous lesions were studied retrospectively. Patients underwent ALA-PDT or surgery and were followed up at 3, 6, 9 and 12 months and then every six months after that. Clinical data were collected and the efficacy and safety of the two treatment methods were compared.
RESULTS: Of the 41 patients with recurrent cervical HSIL after conization, 15 cases received ALA-PDT and 26 received surgery. At the six-month follow-up, the lesions\' complete remission (CR) rate was 93.33 % in ALA-PDT group and 88.46 % in the surgery group. The human papillomavirus (HPV) clearance rates were 66.67 % and 73.08 %, respectively. No significant differences concerning the lesions\' CR rate and the HPV clearance rate were observed between the two groups (P>0.05). At the twelve-month follow-up, the HPV clearance rates were 80.00 % and 91.67 %. No significant differences concerning the HPV clearance rate were observed between the two groups (P>0.05). In the surgery group, the HPV clearance rate and the lesions\' CR rate were lower in patients over 45 years of age (25.00% vs. 81.82 %, P = 0.031; 50.00% vs. 95.45 %, P = 0.052). During the follow-up, there was no significant difference in the recurrence rate between the two groups (P>0.05). In addition, none of the patients progressed. In women treated with ALA-PDT, there was no vaginal bleeding, and no harmful effects on the cervical organizational structure or functions compared to the surgery group, and two women delivered successfully after ALA-PDT treatment.
CONCLUSIONS: The efficacy of ALA-PDT was similar to that of surgery in treating recurrent cervical HSIL following surgery, with fewer side effects.

This study investigated the efficacy of the prophylactic human papillomavirus (HPV) vaccine, which was initiated between 2009 and 2013 in Japan. The study involved 1529 eligible women aged 16-39 years who visited 11 outpatient clinics in Japan for various reasons. These patients underwent HPV genotype analysis and a Pap test of cervical cell samples. A total of 299 women (19.6%) had received the prophylactic HPV vaccine (bivalent:quadrivalent vaccine ratio = 2:1). Of the 5062 participants in the Japanese Human Papillomavirus Disease Education and Research Survey (J-HERS 2011), which was conducted in the pre-vaccination era, 3236 eligible participants were included as controls. In this study (J-HERS 2021), the highest rate of HPV vaccination (53%) was observed in patients aged 22-27 years. Vaccinated individuals exhibited a 49% rate of protection against low-grade intraepithelial lesions (LSILs) and atypical squamous cells, not excluding high-grade squamous intraepithelial lesions (ASCH) or worse (LSIL/ASCH+), and a 100% rate of protection against high-grade squamous intraepithelial lesions (HSILs) or worse (HSIL+). Significant reductions in HPV16 (95%) and HPV18 (100%) infections were noted, but no differences were observed in HPV6 and HPV11 infections. The prevalences of HPV51 and HPV59 increased with vaccination, although these changes were not confirmed in the comparative study with J-HERS 2011. Comparing the prevaccination (J-HERS 2011) and postvaccination (J-HERS 2021) periods, 43%, 51%, 88%, and 62% reductions in HPV16, HPV18, HPV16/18, and HPV31/58 infection rates were observed, respectively. Similarly, 62% and 71% reductions in LSIL/ASCH+ and HSIL+ rates were noted, respectively. There were 88% and 87% reductions in LSIL/ASCH+ and HSIL+ rates in 16-21- and 28-33-year-old patients, respectively. Bivalent or quadrivalent vaccines provided 100% protection against high-grade squamous cell lesions (suggestive of CIN2 or CIN3) in young women aged <39 years at 9-12 years after initiation of Japan\'s first nationwide HPV vaccination program. Cross-protection against HPV31 and HPV58 is likely to occur, although some HPV-type replacements are inconsistent across vaccination regimens. This demonstrates the effectiveness of the HPV vaccine. However, continuous monitoring of cervical cancer and precancer is necessary in younger generations (born 1997-2007), who were rarely vaccinated due to the prolonged suspension of the vaccine recommendations in Japan.

BACKGROUND: This study aimed to compare the efficacy of focused ultrasound (FUS) and the loop electrosurgical excision procedure (LEEP) for the treatment of cervical high-grade squamous intraepithelial lesions (HSILs) among women of reproductive age.
METHODS: Case records of patients aged < 40 years who were treated for cervical HSILs using either FUS or LEEP from September 1, 2020 to May 31, 2022 were retrospectively reviewed. Patients were followed up for cure, recurrence, human papillomavirus (HPV) clearance, and complications within 1 year of treatment. Odds ratios and 95% confidence intervals were determined using univariate and multivariate logistic regression models to analyze the association between disease evidence or HPV clearance and treatment modalities or other covariates.
RESULTS: Of the 1,054 women who underwent FUS or LEEP, 225 met our selection criteria. Among the selected women, 101 and 124 received FUS and LEEP, respectively. There was no significant difference between the FUS and LEEP groups in the cure rate during the 3-6 months of follow-up (89.11% vs. 94.35%, P = 0.085) and recurrence rate during the 6-12 months follow-up (2.22% vs. 1.71%, P = 0.790). Both groups exhibited enhanced cumulative HPV clearance rates; however, the rates were not significantly different between the FUS and LEEP groups (74.23% vs. 82.79%, P = 0.122 during the 3-6 months follow-up; 84.95% vs. 89.17%, P = 0.359 during the 6-12 months follow-up). Furthermore, the incidence of complications caused by the FUS and LEEP techniques was comparable (5.0% vs. 5.6%, P = 0.818).
CONCLUSIONS: We found that FUS and LEEP have similar efficacy, safety, and reliability in treating women (aged < 40 years) with HSILs.