Cervical Intraepithelial Neoplasia Research Articles

Gene expression levels associated with impaired immune response and increased proliferation could serve as biomarkers for women following cervical cancer screening programmes

Human papilloma virus (HPV) infections vary in their oncogenic potential, and whether an infection progresses to cervical intraepithelial neoplasia (CIN) also depends on the immune response. Therefore, the aim of the present study was to explore biomarkers related to the immune system and cell proliferation, in combination with HPV classified as having high (HOP) or low oncogenic potential (LOP), that can possibly guide a more accurate identification of women following cervical cancer screening programmes in need for immediate follow-up with a biopsy. A next-generation sequencing transcriptomic immune profile analysis applied to 28 persistent CIN3 lesions and 14 normal biopsies identified four genes, the immune markers ARG1 and HLA-DQB2 and the tumour markers CDKN2A and KRT7, as possible markers for differentiating between CIN3 and normal tissue. To validate these findings, analysis of the relative gene expression of these markers by use of reverse transcriptase real-time quantitative polymerase chain reaction was performed in an independent cohort of 264 (82 normal, 64 CIN1, and 118 CIN2/CIN3) biopsies, and the data were combined with information on the HOP- or LOP-HPV identified in the biopsies. Statistical analysis was performed with receiver operating characteristic curves, reporting area under the curve (AUC) with 95% confidence intervals (CIs), and logistic regression. Statistically significantly higher median expression levels of CDKN2A (p < 0.001) and KRT7 (p = 0.045) and significantly lower expression of ARG1 (p = 0.012) were found in biopsies with HOP-HPV infections, with no difference detected for HLA-DQB2 (p = 0.82). Models using expression levels of CDKN2A (AUC, 0.91; 95% CI, 0.86–0.95), KRT7 (0.86, 0.81–0.91), or ARG1 (0.78, 0.70–0.85) together with HOP/LOP-HPV class were significantly better than HPV class alone (0.72, 0.66–0.79) in discriminating CIN2/3 versus CIN1 (p < 0.001, p < 0.001, and p = 0.014, respectively).

Cervical intraepithelial neoplasia and cervical cancer in Hunan Province, China, 2020-2023

ObjectiveTo describe the incidence and distribution of cervical intraepithelial neoplasia (CIN) and cervical cancer (CC) for rural women aged 35-64 in Hunan Province, China, 2020-2023.MethodsData were from the Hunan Provincial Cervical Cancer Screening Program in Rural Areas. Most rural women aged 35-64 in Hunan Province attend the program. All women diagnosed with CINs and CCs will be asked to register detailed information, including pelvic examination, diagnosis, age, education level, etc. CINs included low-grade squamous intraepithelial lesions (LSIL) (CIN1), high-grade squamous intraepithelial lesions (HSIL) (CIN2 and 3); CCs included adenocarcinoma in situ (AIS), early invasive cervical cancer (EICC) (stage Ia1 and Ia2) and invasive cervical cancer (ICC) (stage Ib and above). The incidence of CIN and CC is the number of cases per 1000 women. Chi-square tests (χ2) were used to examine if there were significant differences in proportions among different groups.ResultsA total of 4150700 women were included, and 67071 CINs and CCs were identified. The incidence of LSIL, HSIL, AIS, EICC and ICC were 10.63‰(95%CI: 10.53-10.73), 4.98‰(95%CI: 4.91-5.05), 0.06‰(95%CI: 0.06-0.07), 0.23‰(95%CI: 0.22-0.25), and 0.26‰(95%CI: 0.24-0.27), respectively. The proportion of previous pelvic examinations was relatively low in EICC (17.24%) and ICC (17.45%) (χ2 = 236.57, P <0.01), present abnormal examination was relatively high in AIS (51.33%), EICC (49.74%) and ICC (62.45%) (χ2 = 331.15, P <0.01). HPV16 was the most common high-risk type for LSIL (22.01%), HSIL (36.92%), AIS (46.01%), EICC (58.88%), and ICC (64.34%). The proportion of HSIL was relatively high in women aged 35-44 (27.03%), AIS was relatively high in women aged 45-54 (46.39%), EICC (44.24%), and ICC (48.58%) was relatively high in women aged 55-64. The proportion of ICC was relatively high in women with elementary school (38.68%), HSIL (15.10%) and AIS (17.49%) was relatively high in women with senior high school, AIS (1.52%), EICC (0.62%) and ICC (0.75%) was relatively low in women with university and above. (P <0.01).ConclusionWe have described the incidence and distribution of CIN and CC among rural women aged 35-64. These findings were clinically relevant and were useful for clinical counseling and early diagnosis of CC.

The Recurrence Rate of Cervical Intraepithelial Neoplasia After Loop Electrosurgical Excision Versus Cold Knife Conization: A Cross-Sectional Study

Background: Effective cervical intraepithelial neoplasia (CIN) treatment and detection of high-risk recurrence patients is very important. Objectives: The present study aimed to compare the recurrence rate of CIN after loop electrosurgical excision procedure (LEEP) versus cold knife conization (CKC). Methods: This cross-sectional study involved 329 patients who underwent either LEEP (294 cases) or CKC (35 cases) in the colposcopy clinic of referral hospitals between March 2016 and February 2021. The study population was followed up every six months for two years after their first conization to monitor for any recurrence of the disease. Results: There was no significant difference between the two groups regards. Thirty-two patients experienced recurrence within two years after surgery. The rate of CIN recurrent was 30 (10.2%) cases in the LEEP group and 2(5.7%) cases in the CKC group, with no significant differences (P-value = 0.553, RR = 1.78; 95% CI = 0.44-7.15). Conclusions: The present study compared the benefits and harms of LEEP and CKC. The recurrence rate and surgical complications associated with both methods appeared to be similar with no significant differences. However, further high-quality and comprehensive research with a long-term follow-up is necessary to confirm our findings.

2024 Hong Kong College of Obstetricians and Gynaecologists Guidelines for cervical cancer prevention and screening.

Primary prevention of cervical cancer is best achieved by vaccinating girls with a prophylactic human papillomavirus (HPV) vaccine. Despite the high efficacy of such vaccines, cervical cancer screening remains necessary because current vaccines do not offer full protection. Secondary prevention via cervical screening should target all women from age 25 years or at the onset of sexual activity, whichever occurs later, until age 64 years. Screening is recommended at 3-year intervals after two consecutive normal annual cytology results, or at 5-year intervals using HPV-based testing (either HPV co-test with cytology or HPV stand-alone). Women who have undergone hysterectomy with cervix removal for benign disease and have no prior history of cervical dysplasia can discontinue screening. Women with HPV-positive, cytology-negative co-test results should either undergo repeat co-testing in 12 months or immediate HPV16/18 genotyping. Immediate referral of women with positive stand-alone HPV test results for colposcopy without further triage is not recommended. A second triage test using cytology, genotyping for HPV16/18, or p16/Ki-67 dual-stain should be conducted to accurately identify women at high risk for high-grade lesions who thus require colposcopy referral. Women with HPV-positive, cytology-positive co-test results, or high-grade abnormal cytology results should be referred for colposcopy. Treatment with a loop electrosurgical excision procedure is recommended for women with high-grade squamous intraepithelial lesions (HSILs). After HSIL treatment, long-term follow-up with HPV-based testing over 25 years is preferred. When cytology results show atypical glandular cells, colposcopy and sampling of the endocervix and endometrium are recommended.

Exploring the Clinical Signatures of Cervical Dysplasia Patients and Their Association With Vaginal Microbiota.

The vaginal microbiota plays a crucial role in women's health, and an imbalanced vaginal microbiota is linked to various diseases, including human papillomavirus (HPV) infection. However, most available data comes from Western countries and primarily focuses on HPV infection, with only a few studies considering detailed clinical factors to explore the relationship between vaginal microbiota and the development of cervical cancer, especially in China. Our study involved 266 women, including individuals at all stages of cervical dysplasia, and healthy controls with and without HPV infection. We assessed several aspects of the vaginal environment, including vaginal microbiota composition using 16S rRNA gene sequencing, HPV infection status using the standard Roche Cobas method, pH value, age, and H2O2 levels from clinical records, and partner numbers and contraceptive methods obtained through questionnaires. The association of these clinical signatures with cervical dysplasia stages and vaginal microbiota was analyzed. Our findings demonstrate a significant association between vaginal microbiota and cervical dysplasia stages. Patients with cervical dysplasia and cancer showed a substantial increase in HPV 16 infection, a higher prevalence of pH > 5, a lower H2O2 level, and older ages compared to healthy individuals. Additionally, these factors influence the beta diversity of the vaginal microbiota. These results underscore the importance of considering the vaginal microbiota within the cancer microenvironment and highlight the need to integrate all available data to aid in the current diagnosis and understanding of cervical dysplasia and the cervical cancer microenvironment.

Study on the Clinical Characteristics, Persistent Infection Ability and Viral Load of Human Papillomavirus Type 73 Single Infection.

Human papillomavirus (HPV) infection is a main cause of cervical cancer. Different HPV types exhibit significant differences in pathogenicity. Clinical data on HPV73 single infection is limited, this study aimed to analyze the clinical characteristics of HPV73 single infections. We collected cervical exfoliated cells to examine the infection rate and the clinical characteristics of patients with single HPV73 infection, and to investigate the association of viral load, persistent infection, and pathogenicity. The positive rate of HPV73 among women tested was approximately 0.14% (609/435 072). Among 214 HPV73 single infection cases, the number of patients with normal cytology, cervical intraepithelial neoplasia (CIN)1, CIN2, CIN3, and cervical cancer were 182, 24, 5, 1, and 1, respectively. Follow-up data showed that 14.29% (3/21) of CIN1 patients developed to higher-grade lesions, with 3.73% (5/134) of normal patients progressed to CIN. The viral load in the CIN group was significantly higher than that in the normal group (p = 0.001), and the viral load in the persistent infection group was significantly higher than that of the viral-clearance group (p < 0.001). HPV73 single infection can lead to cervical cancer, with relatively low pathogenicity. And high viral load is a crucial factor in its persistent infection and pathogenicity.

Associations of Obesity with Post-Treatment Risks of Cervical Precancer and Cancer.

Individuals with obesity have an increased risk of cervical cancer, in part related to challenges associated with cervical sampling and visualization that result in missed detection of cervical precancers. The influence of obesity on the effectiveness of excisional treatment of detected cervical precancers and post-treatment disease risk is unknown. The aim of this study was to evaluate post-treatment risks of cervical precancer and cancer by body mass index (BMI). This retrospective cohort study included individuals aged 25 years and older undergoing excisional treatment for cervical precancer, either cervical intraepithelial neoplasia (CIN) grade 2 or 3 or adenocarcinoma in situ (AIS) as of January 2017 with follow-up through February 2023. Patients were excluded if they were missing BMI, had cancer upon excision or had hysterectomy in lieu of excision, or were missing a valid referral screening visit. We categorized BMI as: Underweight/Normal (<25 kg/m2), overweight (25 to <30 kg/m2), and obesity (≥30kg/m2), as well as by class (I-III) of obesity. We calculated two-year risks of CIN3 and cancer (combined as CIN3+) using Kaplan Meier methods and evaluated multivariable adjusted associations of BMI with CIN3+ using Cox Proportional Hazards regression analyses, accounting for age at treatment, race and ethnicity, and treatment type. Among 10,614 patients, a total of 680 (6.4%) developed post-treatment CIN3+; most (91%) within two years of treatment. Two-year CIN3+ and cancer risks were highest in those with obesity (8.65%, 95% CI, 7.6-9.9% and 0.79%, 95% CI, 0.5-1.2%, respectively) and lowest in those with normal weight (5.57%, 95% CI, 4.9-6.3% and 0.29%, 95% CI, 0.2-0.5%, respectively). Hazard ratios measuring associations of BMI with risk of post-treatment CIN3+ ranged from 1.19 (95% CI, 1.0-1.4) among those with overweight to 1.89 (95% CI, 1.4-2.6) among those with class III obesity (p-trend <0.0001). A similar trend was observed for cancer, from 1.62 (95% CI, 0.8-3.3) for overweight and 3.50 (95% CI, 1.3-9.3) for class III obesity (p-trend =0.016). Patients with obesity undergoing excisional treatment for cervical precancer have a higher risk of residual or recurrent disease, likely due to incomplete excision.

Declining Prevalence of Human Papillomavirus Co-Infections Among Young Japanese Women With Cervical Cancer and Its Precursors.

Co-infections with human papillomavirus (HPV) of multiple genotypes mainly occur due to increased sexual activity. To address the prevalence and trend of HPV co-infections in Japan, HPV-type-specific data from Japanese women (n = 8128) aged < 40 years and newly diagnosed with cervical abnormalities at 24 hospitals between 2012 and 2023 were analyzed. These included cervical intraepithelial neoplasia grade 1/2 (CIN1/2, n = 2745), CIN3/adenocarcinoma in situ (AIS) (n = 3953), and invasive cervical cancer (ICC, n = 1430). For women enrolled in this study since 2019, information on sexual behaviors was collected via a self-administered questionnaire. Time-trend analyses by disease category showed significant declines in the prevalence of multiple HPV infections in CIN1/2 (49.1%-38.3%, ptrend = 0.0004), CIN3/AIS (44.7%-31.5%, ptrend = 0.0002), and ICC (26.7%-10.5%, ptrend < 0.0001) during the last decade. When these data were analyzed separately for women aged 20-29 and 30-39 years, similar declining trends were observed in each disease category. Using data from 2111 women for whom information on sexual history was available, the number of sexual partners was strongly associated with increased multiple HPV infections (p < 0.0001). In conclusion, the declining prevalence of HPV co-infections in cervical cancer and its precursors may reflect a decrease in sexual activity among Japanese women of reproductive age.

Case-Control Study of Cervicovaginal Beta-/Gamma-HPV Infection in Women with HIV and Its Relation with Incident Cervical Precancer.

We studied cervicovaginal β-/γ-human papillomavirus (HPV) and their relationship to cervical precancer in women with HIV (WWH); having previously reported strong positive associations of β-/γ-HPV with incident head and neck cancer in the general population. Cases (N=124) had cervical intraepithelial neoplasia (CIN)-3 or CIN-2. Controls (N=247) were individually matched 2:1 to cases. Unexpectedly, multivariate analyses found strong inverse associations between β-/γ-HPV and CIN-2/CIN-3 (OR=0.19; 95% CI 0.04-0.86; P=0.03) with Ptrend<0.01. This is, to our knowledge, the first study of β-/γ-HPV and cervical precancer. If confirmed, a strong inverse (protective) association would be of potential clinical and biologic relevance.

A lightweight deep learning method to identify different types of cervical cancer

Cervical cancer is the second most common cancer in women’s bodies after breast cancer. Cervical cancer develops from dysplasia or cervical intraepithelial neoplasm (CIN), the early stage of the disease, and is characterized by the aberrant growth of cells in the cervix lining. It is primarily caused by Human Papillomavirus (HPV) infection, which spreads through sexual activity. This study focuses on detecting cervical cancer types efficiently using a novel lightweight deep learning model named CCanNet, which combines squeeze block, residual blocks, and skip layer connections. SipakMed, which is not only popular but also publicly available dataset, was used in this study. We conducted a comparative analysis between several transfer learning and transformer models such as VGG19, VGG16, MobileNetV2, AlexNet, ConvNeXT, DeiT_tiny, MobileViT, and Swin Transformer with the proposed CCanNet. Our proposed model outperformed other state-of-the-art models, with 98.53% accuracy and the lowest number of parameters, which is 1,274,663. In addition, accuracy, precision, recall, and the F1 score were used to evaluate the performance of the models. Finally, explainable AI (XAI) was applied to analyze the performance of CCanNet and ensure the results were trustworthy.

Triage performance of DNA methylation for women with high-risk human papillomavirus infection.

DNA methylation is a promising biomarker for cervical cancer screening. This study aimed to validate the triage performance of cytological DNA methylation for detecting cervical intraepithelial neoplasia of grade 3 or worse (CIN3+) in women with high-risk human papillomavirus (hrHPV) infection from a large prospective cohort undergoing opportunistic screening in China (METHY3). The triage performance for detecting CIN3+ lesions was compared between HPV16/18 genotyping, a liquid-based cytology (LBC) test, and the PAX1 and JAM3 methylation (PAX1m/JAM3m) test according to cervical pathologic outcomes. Among the 4394 women infected with hrHPV, 1105 had definitive cervical histological findings that were analyzed. For detecting CIN3+, the specificity of HPV16/18(+), the LBC result of ≥atypical squamous cells of undetermined significance (ASCUS), and PAX1m/JAM3m(+) was 66.4%, 23.9%, and 89.6%, respectively, with odds ratios of 4.24 (95% confidence interval [CI], 2.85-6.40), 4.44 (2.27-10.1), and 18.5 (12.1-28.7) (P < .001), respectively. PAX1m/JAM3m(+) had the highest area under the receiver operating characteristic curve (0.790, 95% CI, 0.747-0.832) in the whole cohort and in women of various ages. PAX1m/JAM3m (+) was detected in all patients with cancer (n = 28). Compared with HPV16/18 genotyping and the LBC test, PAX1m/JAM3m testing reduced referrals to colposcopy by 20.64 percentage points and 61.18 percentage points, respectively. PAX1 m /JAM3 m testing is highly specific for detecting CIN3+. As a triage biomarker, it is superior to HPV 16/18 genotyping and LBC testing for women with hrHPV infection.

Study on the clinical characteristics, persistent infection capability and viral load of human papillomavirus type 26 single infection

BackgroundHuman papillomavirus (HPV) infection is the main cause of cervical cancer. Different types of HPV have varying carcinogenic capabilities, and viral load is one of the key indicators of pathogenicity. Currently, there is a lack of clinical data on HPV26. This study analyzed the clinical characteristics of patients with HPV26 single infection.MethodsExfoliated cervical cells were collected for HPV genotyping from women who attended gynecological outpatient clinics or physical examinations. The clinical characteristics of HPV26 single infections in both cross-sectional and follow-up studies were examined, and the association of viral load with HPV26 persistent infection and pathogenicity was investigated.ResultsThe HPV26 positive rate among women visiting hospitals for gynecological medical consultation or physical examination was approximately 0.09% (379/435,072). Among the HPV types tested, the detection rate of HPV26 was 0.37% (379/103,608). In the cross-sectional histopathological study of 101 patients with HPV26 single infection, 62.37% (63/101) presented lesion-free. The numbers of patients with cervical intraepithelial neoplasia (CIN) 1, CIN2, and CIN3 were 25, eight, and five, respectively. Cervical cancer was not detected in any patient. 71 patients attended follow-up examinations as well as HPV26 retesting up to two years, during which, 28.57% (6/21) of CIN1 patients have developed into high-grade lesions, and 9.61% (5/52) of lesion-free patients have progressed to CIN stage. The viral load in the CIN group was significantly higher than that in the lesion-free group (p = 0.012). Similarly, the viral load in the persistent infection group was significantly higher than that in the viral-clearance group (p < 0.001).ConclusionsThe pathogenicity of single HPV26 infections is moderate among high-risk types, warranting the inclusion of HPV26 in expanded screening for HPV. High viral load is an important factor in the persistent infection and pathogenicity of HPV26. Viral load is expected to serve as a screening risk factor for persistent infection and disease progression associated with HPV26.

Participation and relative cost of attendance by direct-mail compared to opt-in invitation strategy for HPV self-sampling targeting cervical screening non-attenders: A large-scale, randomized, pragmatic study.

Broad accessibility to cervical cancer screening and high participation rate is essential to reduce cervical cancer incidence. HPV self-sampling is an alternative to clinician collected cervical samples to increase accessibility and screening coverage. To inform on deployment strategies of HPV self-sampling, this large-scale, randomized, pragmatic study compared two invitation modalities; direct-mail and opt-in. The study included screening non-attenders from the Capital Region of Denmark randomly allocated (1:4) to a direct-mail or opt-in invitation for cervical screening by HPV self-sampling. Primary endpoint was screening participation; secondary endpoints were HPV prevalence and histology outcome. Adherence to follow-up and cost were also evaluated. After exclusion of hysterectomized/non-accessible women, 49,393 women were invited: 9639 by direct-mail, and 39,754 by the opt-in offer. A direct-mail invitation for HPV self-sampling yielded a significant higher participation than an opt-in invitation. HPV self-sample participation for direct-mail was 25.2% (n = 2426), opt-in participation was 20.2% (n = 8047), adjusted OR = 1.27, 95% CI 1.20-1.34. Participation increased with age (p < .0001) for both strategies and decreased with screening history of non-attendance (p < .0001). Interaction between invitation strategy and age/screening history was found; more women below 50 years of age participated by direct-mail compared to opt-in (p < .0001) and higher participation by direct-mail group was found in women with a short history of non-attendance (p < .0001). Participation of long-term unscreened women was similar between arms. The relative cost was ≈14 HPV self-sample kits distributed per additional participant by direct-mail over opt-in. HPV prevalence, adherence to follow-up, and detection of high-grade cervical intraepithelial neoplasia was similar between invitation strategies.

Assessment of systemic reaction to inflammation induced by photodynamic therapy in cervical intraepithelial neoplasia

Photodynamic therapy is a curative treatment of human papillomavirus-associated diseases that provides a selective effect leading to the destruction of pathological cells containing the virus. The retrospective study aimed to determine the role of systemic inflammatory reaction induced by photodynamic stimulation in low- and high-squamous intraepithelial lesion treatment. Methods143 patients with confirmed human papillomavirus-associated cervical intraepithelial neoplasia underwent photodynamic therapy with Photolon and activation in the range of 662 nm. All patients underwent colposcopy, histologic study, HPV DNA analysis, CBC, and immunogram. The chi-square criterion was used to evaluate differences before, 5 days post, and 3 months after PDT; a P value <0.05 was considered significant. ResultsA complete regression in patients with low-squamous intraepithelial lesion (n=117) was achieved 3 months after PDT in 89.7% of cases (105/117) while it persisted in 12 patients. Complete regression in patients with high-squamous intraepithelial lesion (n=26) was achieved in 92.3% (24/26), one patient retained with the lesion, and another one had partial regression in the form of lower grade lesion. On the 5th day post-PDT, the formation of dense fibrin in photodynamic effect was noted on colposcopy, and changes in CBC, accompanied by statistically significant neutrocytosis, increased ESR and other indicators of reactive inflammation were recorded. Patients noted increased body temperature up to 37.8±0.5°C in 88% of cases. ConclusionOne of the mechanisms of PDT`s antitumor and antiviral action is the development of acute inflammation in response to cytotoxic action on cells and vascular response in the form of pathological area devascularization. Such reactive inflammation activates all parts of the immune system. Changes on day 5 post-PDT in inflammatory parameters in CBC and IL-1, IL-6 and TNF-α markers correlate with the clinical picture of the post-photodynamic effect.

Transcriptional and post-transcriptional regulation of CARMN and its anti-tumor function in cervical cancer through autophagic flux blockade and MAPK cascade inhibition

BackgroundLncRNAs play essential roles in multiple tumors. However, research on genome-wide lncRNA alterations and their functions in cervical cancer (CC) is limited. This study aims to explore key lncRNAs in CC progression and uncover the molecular mechanisms involved in the development of CC.MethodsIn this study, we analyzed 30 tissues from CC, cervical intraepithelial neoplasia (CIN), and normal (NOR) using transcriptome sequencing and weighted gene co-expression network analysis to establish gene modules related to the NOR-CIN-CC transition. Machine learning diagnostic models were employed to investigate the role of lncRNAs in this transition. Molecular biological experiments were conducted to elucidate the potential mechanisms of CARMN in CC, with a particular focus on its transcriptional and post-transcriptional regulation of abnormal expression in CC.ResultsCARMN was identified as a hub gene in two modules significantly associated with the NOR-CIN-CC transition. Analysis using ten machine learning models confirmed its critical role in this progression. The results of RNA-seq, qPCR and RNAScope performed in another cohort of 83 cervical tissues all showed that CARMN was significantly downregulated in CC. CARMN significantly enhanced the interaction between Keap1 and Nrf2, leading to increased ROS levels. The elevated ROS levels suppressed the Akt/mTOR signaling pathway, leading to autophagy arrest via autophagic flux blockade. Additionally, CARMN interacted with TFAP2α to repress MAPK13 transcription, further inhibiting the MAPK cascade. A promoter SNP (rs12517403) was found to increase CC risk (OR = 1.34, 95% CI = 1.11–1.61) and reduce CARMN expression by decreasing SP1 binding. Furthermore, the RNA binding proteins that could modulate CARMN RNA stability were also determined using RNA-pulldown assay. The results demonstrated that YBX1, a component of the coding region instability determinant (CRD)-mediated mRNA stabilization complex, promoted CARMN RNA stability. DHX9, another component of complex, acted as a scaffold to bridge YBX1 and CARMN.ConclusionsCARMN exerts an anti-cancer effect in CC progression by inhibiting the Akt-mTOR and MAPK signaling pathways. rs12517403 and the YBX1/DHX9 complex are key mechanisms influencing its transcription and stability in CC cells. CARMN represents a promising biomarker for CC diagnosis and therapeutic target.

The Effect of Interventions Based on the Information-Motivation-Behavioral Skills Model on the Human Papillomavirus Vaccination Rate Among 11-13-Year-Old Girls in Central and Western China: Protocol for a Randomized Controlled Trial.

Persistent infection of high-risk human papillomavirus (HPV) can lead to cervical intraepithelial neoplasia, cervical cancer, and even death. HPV vaccination for girls aged 9-14 years can effectively prevent the occurrence of cervical cancer. Some Chinese provinces and cities have launched free HPV vaccination programs for school-age girls; however, due to the lack of supportive government policies, the high price and supply shortage of HPV vaccines, and vaccine hesitancy, some parents refuse to vaccinate their daughters. This protocol reports the design of a randomized controlled trial (RCT) aiming to explore the efficacy of a digital HPV vaccination education intervention based on the information-motivation-behavioral skills (IMB) model in improving the HPV vaccination rate among 11-13-year-old girls in central and western China. A multicenter intervention study based on an online applet will be conducted in December 2024, and about 750 eligible parents of 11-13-year-old girls will be assigned in a 1:1 ratio to an intervention group receiving 7-day digital HPV vaccination education based on the IMB model or a control group using non-HPV publicity materials. Free HPV vaccination pilot projects will be carried out among this population by our research team in central and western China (some parents might refuse to vaccinate their daughters). All participants will be asked to complete online questionnaires at baseline; postintervention; and 1 week, 1 month, and 3 months after the intervention. The primary outcome of this study will be receipt of the first HPV vaccination within 3 months. Data will be analyzed based on an intention-to-treat approach, and Stata 16.0 will be used for statistical analysis. This study aims to improve the HPV vaccination rate among 11-13-year-old girls and will examine the impact of a digital HPV vaccination education intervention based on the IMB model. The findings of this study may offer promising intervention measures for HPV vaccine hesitancy in low-health-resource areas in the future. Chinese Clinical Trial Registry, ChiCTR2300067402; https://tinyurl.com/v5zt4hc9. PRR1-10.2196/58873.

Risk of High-Grade Cervical Dysplasia in Older Patients With a Positive Human Papilloma Virus Cervical Screening Test

Introduction The Australian National Cervical Screening Program has mandated management algorithms that are uniform across all age groups, but evidence is emerging that perhaps the risk of high-grade squamous intraepithelial lesion (HSIL) may decrease in the postmenopausal period. Objective The aim of the study is to identify if patients ≥50 years of age referred to a tertiary colposcopy service have a different risk of HSIL or greater (+). Materials and Methods This is a retrospective cohort study of 3239 referrals to a hospital colposcopy clinic with a positive human papillomavirus (HPV) cervical screening test between December 2017 and May 2023. Patients were included if they were aged 25–74 years, had a cervix, and completed an outpatient colposcopic assessment. Medical records were analyzed to determine the incidence of HSIL+ for each age group and compared them using χ2 and multivariable regression. Results The overall incidence of invasive carcinoma was 0.93% and HSIL/adenocarcinoma-in-situ was 20.38%. Patients ≥50 years of age were less likely to have HSIL or greater diagnosed than those &lt;30 (p &lt; .0001) or those 30–49 (p &lt; .0001), even after considering referral HPV subtype and reflex cytology (OR = 0.45, 95% CI = 0.34–0.59). The risk of invasive carcinoma in those aged ≥50 was no different than those aged 30–49 (p = .982). Conclusions We observed a lower incidence of HSIL or greater with increasing age even after considering referral HPV subtype and reflex cytology. As further data emerges regarding the risk of high-grade disease in those ≥50 years of age, refinement of the risk-based screening algorithm to account for advanced age may be required.

Cervical intraepithelial neoplasia and cervical cytology in pregnancy.

Cervical cancer screening during pregnancy presents unique challenges for cytologic interpretation. This review focuses on pregnancy-associated cytomorphological changes and their impact on diagnosis of cervical intraepithelial neoplasia (CIN) and cervical cancer. Pregnancy-induced alterations include navicular cells, hyperplastic endocervical cells, immature metaplastic cells, and occasional decidual cells or trophoblasts. These changes can mimic abnormalities such as koilocytosis, adenocarcinoma in situ, and high-grade squamous intraepithelial lesions, potentially leading to misdiagnosis. Careful attention to nuclear features and awareness of pregnancy-related changes are crucial for correct interpretation. The natural history of CIN during pregnancy shows higher regression rates, particularly for CIN 2, with minimal risk of progression. Management of abnormal cytology follows modified risk-based guidelines to avoid invasive procedures, with treatment typically deferred until postpartum. The findings reported in this review emphasize the importance of considering pregnancy status in cytological interpretation, highlight potential problems, and provide guidance on differentiating benign pregnancy-related changes from true abnormalities. Understanding these nuances is essential for accurate diagnosis and proper management of cervical abnormalities in pregnant women.

Expanded HPV Genotyping by Single-Tube Nested-Multiplex PCR May Explain HPV-Related Disease Recurrence.

The role of the human papillomavirus (HPV) in the establishment of cervical cancer has driven studies to find more effective methods of viral detection so that early intervention strategies can be performed. However, the methods still have limitations, especially regarding detecting the different genotypes simultaneously. We have developed a high-throughput system using a single-tube nested-multiplex polymerase chain reaction (NMPCR) for the detection of 40 HPV genotypes using capillary electrophoresis. The NMPCR assay was compared to the Hybrid Capture 2 assay (HC2) with 40 women from the Northeast of Brazil (São Luis, MA), a high endemic region, where the HPV positivity was 75% and 37.5%, respectively. These results were validated by performing a molecular epidemiological study on 5223 Brazilian women undergoing gynecological examinations from 2009 to 2017, who presented with an HPV prevalence of 59%. Multiple infections were found in 62.5% and 58% of the patients from the endemic region and from the Brazilian women population, respectively, mostly presenting high-risk genotypes (90.5% and 60%, respectively). Considering cervical intraepithelial neoplasia and adenocarcinomas, the sensitivity and specificity were 97.5% and 100%, respectively. The NMPCR assay was also capable of identifying viral subtypes in cases of multiple infections, even with low viral loads (10-6 ng/µL of HPV DNA). The NMPCR test is a promising and robust tool for HPV diagnostics and a screening tool for prevention of cervical cancer.

High acceptability of point-of-care HIV testing at the colposcopy outpatient clinic in hospitals in the Netherlands.

Cervical cancer and its precursor are labeled as HIV indicator conditions, justifying the recommendation of HIV testing for all patients. This study aimed to assess the acceptance and patients' and gynecologists' perceptions on HIV testing in patients with cervical dysplasia at the colposcopy outpatient clinic in hospitals in the Netherlands. A cross-sectional study was conducted between May 2021 and February 2023 to implement point-of-care HIV testing in five hospitals in the Rotterdam region, the Netherlands. We included patients aged 18 years and older, without documented HIV, presenting with cervical dysplasia. The primary outcome was the HIV test acceptance rate. Secondary outcomes were the HIV positivity rate and the association between dysplasia severity and test acceptance. We also assessed patients' and gynecologists' perspectives on this testing strategy with a questionnaire. Of 563 patients, 523 accepted HIV testing, resulting in a test acceptance rate of 92.9% (95% confidence interval, 90.45%-94.88%). Testing rates were consistent among participating hospitals (91.6%-100.0%) None of the patients tested positive for HIV. Severity of dysplasia was not associated with test acceptance (P = 0.768). Most patients (n = 500, 96.0%) reported good or higher experience with this testing strategy. The main barriers for gynecologists to offer HIV testing were lack of time (n = 22, 33.9%) and fear to offend a patient (n = 7, 12.5%). Less than half (n = 19, 39.3%) of gynecologists believed an HIV test should be offered to all patients with cervical dysplasia. Point-of-care HIV testing at colposcopy outpatient clinics was well accepted by patients. The data indicate that the primary barrier lies with the physicians to offer such testing.