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.

UNASSIGNED: This study aimed to evaluate the prevalence of multiple high-risk (HR) human papillomavirus (HPV) infections in women with human immunodeficiency virus (HIV) compared to negative controls. This study also aimed to assess the impact of multiple HR-HPVs on the risk of high-grade squamous cervical lesions (HSILs) among women with HIV.
UNASSIGNED: We performed a systematic search of PubMed/Medline, Scopus, Cochrane databases, and ClinicalTrials.gov from 1 January 2004 to 30 June 2023, including screenings and clinical studies evaluating the rates and role of multiple HPV infections in squamous intraepithelial lesions (SILs). Three reviewers independently screened the abstracts of the selected studies and extracted data from full-text articles. The data were subsequently tabulated and compared for consistency. The bias associated with each included study was evaluated according to the OSQE method.
UNASSIGNED: Forty-seven studies meet definitive inclusion criteria. The quality of the observations was considered low in 26 of the included studies and moderate in 21 of the included studies. In comparative screening studies, the pooled prevalence of multiple HR-HPV was 39.1% (95% CI = 33.7-44.7) among women with (n = 1734) and 21.6% (95% CI = 17.3-26.1) in those without HIV infection (n = 912) (OR = 2.33, 95% CI = 1.83-2.97, I 2 = 2.8%). The pooled ORs of HR-HPV multiple infections were similar in African (OR = 2.72, 95% CI = 1.89-3.9) and non-African countries (OR = 2.1, 95% CI = 1.46-3, p for difference = 0.96). Among women with HIV, the risk of HSIL diagnosed either by cytology or histology was higher among those with overall (OR = 2.62, 95% CI = 1.62-4.23) and HR multiple infections than those with single HPV infection (OR = 1.93, 95% CI = 1.51-2.46). Among women with HIV, the excess rates of multiple HPV infections and the excess risk of associated HSIL were consistent across studies including both HIV-naïve subjects and those on antiretroviral therapy, as well as in studies with different rates of immunocompromised women. When study quality (low vs. moderate) was used as a moderator, the results were unchanged.
UNASSIGNED: Multiple HR-HPV infections are common among women living with HIV and are associated with an increased prevalence of HSIL. These associations were also confirmed in studies with high rates of antiretroviral therapy and low rates of immunocompromise.Systematic Review Registration: PROSPERO [registration number: CRD42023433022].

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.

We assessed cumulative detection and determinants of anal high-grade squamous intraepithelial lesions (HSILs) in men who have sex with men living with human immunodeficiency virus and who underwent 3 visits over 2 years, with cytology and high-resolution anoscopy, within the ANRS-EP57-APACHES study. The cumulative HSIL detection rate was 33% (134 of 410), of which 48% HSILs were detected at baseline. HSIL detection varied considerably by center (from 13% to 51%). The strongest HSIL determinants were baseline human papillomavirus 16 (adjusted odds ratio, 8.2; 95% confidence interval, 3.6-18.9) and p16/Ki67 (4.6 [2.3-9.1]). Repeated annual cytology and high-resolution anoscopy improved HSIL detection but did not fully compensate for between-center heterogeneity.

Anal cancer is caused by human papillomavirus (HPV), particularly HPV-16, and is preceded by anal high-grade squamous intraepithelial lesions (HSILs). The incidence of anal cancer is highest among men who have sex with men (MSM) living with HIV (MSMLWH) and increases with age. However, most previous studies of anal HPV infection and anal HSIL were performed on men under 50 years old, and relatively little is known about HSIL among older MSMLWH or MSM not living with HIV (MSM-Not-LWH).
We enrolled MSM who were aged 50+ during 2018-2022 in San Francisco, CA.
One hundred twenty-nine MSMLWH and 109 MSM-not-LWH participated. All participants had anal HPV DNA testing (Atila Biosystems) and high-resolution anoscopy with a biopsy of visible lesions.
Among MSMLWH, 47% had anal HSIL, 19% had HPV-16, and 51% had other oncogenic anal HPV types (excluding HPV-16). Among MSM-not-LWH, 37% had anal HSIL, 22% had HPV-16, and 34% had other oncogenic anal HPV types. Increasing age was not statistically associated with prevalent HSIL, HPV-16, or other oncogenic HPV infections in MSMLWH or MSM-not-LWH. HPV-16 (odds ratio: 45.1, 95% confidence interval: 15.8-129); other oncogenic HPV types (odds ratio: 5.95, 95% confidence interval: 2.74-12.9) were associated with increased odds of anal HSIL, adjusted for age, income, education, and HIV status.
The prevalence of oncogenic anal HPV, anal HPV-16, and anal HSIL remains very high in older MSMLWH and MSM-not-LWH. With recent evidence showing that treating anal HSIL prevents anal cancer, MSM aged 50+ should be considered for anal cancer screening.

Men who have sex with men (MSM) with HIV are at high risk for squamous intraepithelial lesion (SIL) and anal cancer. Identifying local immunological mechanisms involved in the development of anal dysplasia could aid treatment and diagnostics. Here, we studied 111 anal biopsies obtained from 101 MSM with HIV, who participated in an anal screening program. We first assessed multiple immune subsets by flow cytometry, in addition to histological examination, in a discovery cohort. Selected molecules were further evaluated by immunohistochemistry in a validation cohort. Pathological samples were characterized by the presence of resident memory T cells with low expression of CD103 and by changes in natural killer cell subsets, affecting residency and activation. Furthermore, potentially immunosuppressive subsets, including CD15+CD16+ mature neutrophils, gradually increased as the anal lesion progressed. Immunohistochemistry verified the association between the presence of CD15 in the epithelium and SIL diagnosis for the correlation with high-grade SIL. A complex immunological environment with imbalanced proportions of resident effectors and immune-suppressive subsets characterized pathological samples. Neutrophil infiltration, determined by CD15 staining, may represent a valuable pathological marker associated with the grade of dysplasia.

OBJECTIVE: 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.

UNASSIGNED: Cancer has surpassed infectious diseases and heart ailments, taking the top spot in the disease hierarchy. Cervical cancer is a significant concern for women due to high incidence and mortality rates, linked to the human papillomavirus (HPV). HPV infection leads to precancerous lesions progressing to cervical cancer. The cervix\'s external os, near the vagina, hosts various microorganisms. Evidence points to the link between vaginal microbiota and HPV-induced cervical cancer. Cervical cancer onset aligns with an imbalanced Th1/Th2 immune response, but the role of vaginal microbiota in modulating this imbalance is unclear.
UNASSIGNED: In this study, we collected vaginal samples from 99 HPV-infected patients across varying degrees of lesions, alongside control groups. These samples underwent bacterial DNA sequencing. Additionally, we employed Elisa kits to quantify the protein expression levels of Th1/Th2 cytokines IL2, IL12, IL5, IL13, and TNFa within the centrifuged supernatant of vaginal-cervical secretions from diverse research subjects. Subsequently, correlation analyses were conducted between inflammatory factors and vaginal microbiota.
UNASSIGNED: Our findings highlighted a correlation between decreased Lactobacillus and increased Gardenerella presence with HPV-induced cervical cancer. Functionally, our predictive analysis revealed the predominant enrichment of the ABC transporter within the vaginal microbiota of cervical cancer patients. Notably, these microbiota alterations exhibited correlations with the production of Th1/Th2 cytokines, which are intimately tied to tumor immunity.
UNASSIGNED: This study suggests the potential involvement of vaginal microbiota in the progression of HPV-induced cervical cancer through Th1/Th2 cytokine regulation. This novel insight offers a fresh perspective for early cervical cancer diagnosis and future prevention strategies.

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.