Cervix Research Articles

EdgeNeXt-SEDP for cervical adenocarcinoma HPV-associated and non-HPV-associated diagnosis and decision support.

Background .Uterine leiomyomas are the most common benign tumors of the female reproductive system, arising from the overgrowth of smooth muscle tissue within the uterus. Typically, they present as solid, spherical masses that are firmer than the surrounding uterine muscle layer. Onset generally occurs between the ages of 30 and 50, with these tumors often located in the uterine body or cervix. Some women may experience gradual tumor enlargement, accompanied by symptoms such as vaginal bleeding, lower abdominal pain, frequent urination, and constipation. In such instances, surgical treatment should be considered the first choice. Case summary In this case, A 59-year-old woman presented with a large, soft, and irregularly shaped uterine leiomyoma, formed by the fusion of hundreds of smaller fibroids, which had metastasized to the sigmoid colon.Immunohistochemical analysis further demonstrated that benign uterine leiomyomas may present with morphological features, consistency, and an invasive growth pattern akin to malignant tumors. Innovations Uterine leiomyomas are benign tumors that rarely metastasize; however, case reports have documented instances of distant metastasis. Conclusion The purpose of this study is to report a case of a uterine leiomyoma with intestinal metastasis, analyze its rare characteristics and invasive growth pattern, and enhance the understanding of this tumor.

Background/AimRegional differences in genomic mutation profiles of uterine cervical cancer have been reported. Japanese people are divided into two genetic background clusters, originating from mainland Japan and Okinawa. Okinawa is an island prefecture surrounded by the sea, located more than 800 km from the southernmost point of mainland Japan. No studies have examined gene mutation profiles of cervical cancer in Okinawa. This study aimed to investigate the mutation profile of cervical cancer in Okinawa.Patients and MethodsTwenty-three patients with biopsy-proven squamous cell carcinoma and adenocarcinoma of the intact uterine cervix who were treated with definitive radiotherapy were analyzed. Genomic DNA was extracted from fresh frozen tissue samples collected by tumor biopsy prior to treatment. Variants of 224 cancer-related genes were identified using next-generation sequencing.ResultsA total of 29 gene mutations were observed in 16 patients, including nine genes mutated in multiple samples: SCN7A (17%), PIK3CA (13%), FGFR4 (13%), USP6 (13%), SETD2 (9%), KIT (9%), TSC1 (9%), SERPING1 (9%), and NOTCH3 (9%). Compared to a report from mainland Japan, significant differences in mutation frequency were observed in PIK3CA, FBXW7, and ARID1A. Significant mutations in ARID1A, FBXW7, PTEN, TP53, and EP300, reported as relatively common in cervical cancer in other regions were not detected in this study. The rate of 2-year overall survival and progression-free survival was 95.5% and 73.4%, respectively.ConclusionGene mutation profiles of cervical cancer in Okinawa may differ from those in other regions.

Investigating the potential of combining Raman spectroscopy and machine learning for gestational age classification in rat cervical tissue.

Disclosure: K.L. Yamamoto: None.Introduction: Mullerian agenesis occurs in roughly 1 in 4,500 to 5,000 females and typically presents as primary amenorrhea in female children. Its etiology is unclear, however patients with Mullerian agenesis are found to have hypoplasia or agenesis of structures derived from the Mullerian ducts, which include the upper vagina and the uterus. Other aspects of the female reproductive tract, such as the ovaries, are often structurally preserved and function normally leading to development of sexual secondary characteristics. Case: A 14 year old female presented to her pediatrician with complaints of amenorrhea and delayed development, with her exam notable for scant pubic hair but otherwise no development of secondary sexual characteristics including breast growth. Her initial labs denoted a hypergonadotropic hypogonad state, with an undetectable serum estradiol level and serum FSH and LH levels of 143.2 mIU/L and 62 mIU/mL respectively. Her other workup included a 46,XX karyotype, normal prolactin level of 16.1 ng/mL, TSH level of 2.09 mIU/L, total testosterone level of 29 ng/dL, a negative 21-hydroxylase antibody, a normal 17-hydroxyprogesterone level, and an anti-mullerian hormone level of less than 0.003 ng/mL. A pelvic ultrasound showed unusually small ovaries without any evidence of a cervix or uterus, with subsequent abdominal MRI showing no distinct follicle containing ovaries and the absence of a uterus and cervix. She was then referred to pediatric endocrinology, where she was given a diagnosis of Mullerian agenesis and started on escalating estradiol patch doses for puberty induction. She was counseled that fertility would be limited to in vitro fertilization with surrogacy. Roughly one year after initiation of estradiol, she began to note not only development of secondary sexual characteristics, but also monthly cyclical vaginal bleeding. A pelvic exam was performed where she was found to have a visible cervix and palpable uterus with follow-up ultrasound showing a uterus measuring 6.4 x 2.0 x 2.9 cm and a right ovary measuring 2.0 x 1.2 cm; her left ovary was not visualized. At this point, she was given a new diagnosis of 46,XX gonadal dysgenesis and started on monthly medroxyprogesterone acetate for endometrial protection.Conclusion: In a female patient with gonadal dysgenesis and resultant estrogen deficiency, initially compromised uterine growth can result in a uterus too small to see on imaging and a misdiagnosis of Mullerian agenesis until estradiol therapy is started, after which uterine growth can occur and subsequently be visualized.Presentation: Saturday, July 12, 2025

BackgroundSince 2020, co-testing for women over the age of 35 has been a new strategy for cervical cancer screening in Germany. In this study, we investigated the added value of co-testing in organized cervical screening for the German screening population.MethodsA total of 1956 women were referred to our large dysplasia consultation institution due to abnormal screening results in the first round of screening between 2020 and 2022. The endpoint of this retrospective study was the posttest probability of a CIN 2+/CIN 3 + lesion on the cervix uteri. In addition, the influence of HPV subtypes on the endpoints was investigated.ResultsCIN 2 + or CIN 3 + lesions were diagnosed in 21.6% and 13.0%, respectively, of the patients. The probability of severe dysplasia increases with the grade of cytological abnormality and is dependent on the HPV subtype. The probability for detecting invasive cervical cancer (16 patients in total) was significantly higher for women with HPV16 infection than for women with HPV infection of other high-risk types (odds ratio 11.18; 95% confidence interval 3.01, 40.81). CIN 2 + lesions were diagnosed in 10.1% of patients with normal cytology.ConclusionsCIN 2 + lesions could be detected in more than every 5th woman with an abnormal screening result. The proportion of CIN 3 + patients was significantly higher in the presence of HPV 16.

ABSTRACT Objectives: to verify the impact of the COVID-19 pandemic on the diagnosis of cervical cancer and changes in the number of histopathological exams performed in the years 2019 to 2020 in the city of Araguaína-Tocantins. Methods: cross-sectional, descriptive and quantitative epidemiological study about the registered numbers of cervical cancer in the city of Araguaína – Tocantins in the period from 2019 to 2021 of the COVID-19 pandemic. Data collection was carried out in April 2022, through INCA and DATASUS. The analyzed inclusion variables were: number of new cases per year and histological type of malignant neoplasm (squamous cell carcinoma and adenocarcinoma). Results: between the period from 2019 to 2021, there was a 33.5% drop in the number of histopathological exams performed in the city of Araguaína-TO, on the other hand, there was a significant decrease in the recorded numbers of severe lesions of the uterine cervix (NIC III) during the same period. When it comes to histological subtypes, there was only one case of each type of adenocarcinoma and a 75% drop in the invasive epidermoid type compared to the time before the pandemic. Conclusion: it is clear, therefore, that the spread of COVID-19 changed health care and diagnosis of uterine cancer in the Araguainense population. Keywords: Epidemiological Study. Cancer. Cervix.

To compare the outcomes of laparoscopic pectopexy (LP) with uterine preservation between mesh placement anterior to the cervix uteri and mesh placement posterior to the cervix uteri. A retrospective cohort study of 72 women who underwent LP for stage III or IV apical pelvic organ prolapse (POP) was conducted: 48 with mesh placement anterior to the cervix (group I) and 24 with mesh placement posterior to the cervix (group II). The primary outcome was the rate of postoperative recurrences in both groups. The secondary outcome was the change in quality of life, as evaluated by comparing the results of the prolapse quality of life (P-QOL) questionnaire completed pre- and postoperatively. The mean age (58.27 ± 9.85 vs 59.04 ± 9.93years; p = 0698) and mean follow-up period (24.85 ± 5.12 vs 23.17 ± 6.93months; p = 0.323) were similar between the groups. Demographic characteristics and operative time (73.23 ± 14.10 vs 77.08 ± 29.52min, p = 0.407) were similar between the groups. No intraoperative or postoperative complications were noted in any of the groups. Recurrence (12.5% vs 8.3%, p = 0.710) and reoperation rates (4.2% vs 8.3%, p = 0.597) did not differ significantly between the groups. When the pre- and postoperative changes in the P-QOL questionnaire scores were compared between the two groups, the positive change in POP symptoms, sleep/energy, severity of symptoms and total scale score was more significant in group I. Other scale scores were similar between the two groups. In regression analysis, preoperative Ba, D, Ap and Bp points were found to be significant predictors. An increase in Ba and Ap values increased the likelihood of posterior mesh placement, while an increase in D and Bp values increased the likelihood of anterior mesh placement. In laparoscopic pectopexy, placing the mesh anterior or posterior to the cervix has similar results.

Evaluation of the efficacy of topical photodynamic therapy against cervical HPV infection.

In this study, we investigated human epidermal growth factor receptor 2 (HER2) aberrations, including gene amplification and mutation, and protein expression in 123 small cell lung carcinomas (SCLC) and 128 extrapulmonary small cell neuroendocrine carcinomas (EP-SCNC) samples. Among the EP-SCNC cohort, HER2 mutations were found in 5.5% of samples (7/128); urinary bladder (4 cases), and one case each in samples from the colon, anal canal, and uterine cervix. In SCLCs, HER2 mutations were rare, detected in only 0.8% (1/119) of cases. We also identified eight EP-SCNCs and five SCLC cases with HER2 gene variants of uncertain significance (VUS). HER2 gene amplification was detected in 2.3% (3/128) of EP-SCNCs, but no amplification was found in SCLCs. The differences in HER2 mRNA expression were not statistically significant among tumor groups in the EP-SCNCs and SCLCs cohorts. RNA-seq analysis revealed high HER2 mRNA expression in seven EP-SCNCs and four SCLCs. An immunohistochemistry (IHC) analysis of 10 available tumors with high mRNA expression revealed HER2 protein positivity in 8 cases. The prognostic value of HER2 overexpression in EP-SCNC patients was not established in our study. Furthermore, EP-SCNC patients with high HER2 mRNA expression were generally younger, with a mean age of 60years. These findings highlight the potential of HER2 as a therapeutic target in EP-SCNC, warranting further investigation into its clinical implications.

The aim of this study was to examine the efficacy and safety of methadone for refractory cancer pain caused by pelvic floor lesions. Between April 2016 and September 2023, we retrospectively investigated all cases in which methadone was administered by our Palliative Care Team for refractory cancer pain due to pelvic floor lesions, based on the electronic medical records. The extracted cases totaled 36 (21 females), and the age was 55.1 ± 15.1years. The primary sites of malignancy were rectum, colon, and uterine cervix, each of which accounted for nine cases, and others in nine. The causes of refractory pain included pelvic tumors in 36, sacral metastasis/infiltration in 7, and others in 11 (with some overlaps). The prior opioid dosage (oral morphine equivalent) (median, (IQR)) was 168.0 (95.3, 352.5) mg/day. The starting, maximum, and final doses of methadone were 20.0 (10.0, 20.0), 20.0 (13.8, 40.0), and 20.0 (10.0, 37.5) mg/day, respectively, with a treatment duration of 28.0 (16.0, 97.5) days. The pain intensity in NRS on the day before (before) and 7days after (after) the introduction of methadone was 6.0 (5.0, 8.0) and 4.0 (2.0, 5.0), respectively (p < 0.001). The numbers of rescue medications before and after the introduction of methadone were 4.0 (3.0, 5.0) and 3.0 (1.0, 4.0) times/day, respectively (p = 0.0015). Side effects that led to the discontinuation of methadone included nausea and dizziness in one case. Methadone is suggested to be an effective and safe treatment option for refractory cancer pain due to pelvic floor lesions.

Blood supply of the uterus raised interest of the scientists since early 19th century. Fundamental works of anatomists from German circle brought not only solutions but also new questions. Nowadays knowledge on the vasculature of the female internag genital organs plays leading role in many procedures, mostly endovascular, i.e. embolisation techniques used for treatment of uterine fibroids, ectopic pregnancies, bleedings etc. This paper brings a short summary of our knowledge on the vascularization of the uterus with special respect to the uterine cervix. It shows the path which led the scientists from ancient times until the modern period to discover the mysteries of vascular anatomy of this specific area.

BackgroundWorldwide, human papillomavirus (HPV) is a common sexually transmitted infection affecting at least 50% of sexually active individuals at some point during their Life. The worldwide prevalence among women is 11.7%, and the highest prevalence is in sub-Saharan Africa (24%). Persistent HPV infection with high-risk genotypes is now a well-established cause of cervical cancer (CC) and it is demonstrated that they are present in 99.7% of CC cases worldwide. The main purpose of the study was to determine the epidemiology of HPV infection of the uterine cervix among women in Adama, Ethiopia.MethodA cross-sectional study was conducted among 383 women in Adama, Ethiopia, from March to June 2023. A systematic sampling technique was employed and data were collected using a pretested, structured questionnaire. The data were entered into Epi-info 7 and analysed using SPSS version 26. Binary logistic regression for bivariate and multivariate analyses with adjusted odds ratios (AORs) and 95% CIs were used to identify factors associated with HPV infection. The level of significance was defined as a p-value < 0.05.ResultsThe overall prevalence of HPV infection was 26.6%, with high-risk (hr) HPV genotypes. HPV-16 and HPV-18 constituting 22.5% and 5.9%, respectively. “Other HR-HPV” genotypes accounted for 63.7%. Being divorced (AOR = 2.96: 95% CI: 1.18, 7.40), having post-coital bleeding (AOR = 7.97: 95% CI: 2.17, 29.24), having an early sexual debut (AOR = 3.59: 95% CI: 1.69, 7.65), having multiple sexual partners (AOR = 5.25: 95% CI: 1.73, 15.96), having sexually transmitted infections (AOR = 2.36: 95% CI: 1.32,4.20) and being HIV-positive (AOR = 12.37: 95% CI: 4.57, 33.48) were identified as independent factors significantly associated with HR-HPV infection.ConclusionThere was a greater prevalence of HPV infection in the study area than the worldwide prevalence 11.7%. “Other HR-HPV” genotypes were the major oncogenic HR-HPV genotypes identified. Multiple factors were identified as independent factors significantly associated with HR-HPV infection. Awareness creation campaigns and educational programmes about the prevention of HPV infection and associated risk factors need to be implemented in the community.

A Pilot Study to Assess the Efficacy and Safety of Capecitabine-Based Chemoradiotherapy for Cisplatin-Ineligible Patients with Squamous Cell Carcinoma of the Uterine Cervix

Cervical cancer remains a global health challenge with substantial disparities between countries. High-quality colposcopy is essential for cervical cancer prevention, yet training opportunities remain inadequate worldwide. We developed the Intelligent Digital Education Tool for Colposcopy (iDECO) to address training gaps and evaluated the effect across diverse international settings. Six pre-post interventional training programmes were conducted in China, Mexico, and Mongolia from December 2024 to May 2025. A total of 369 trainees from 87 centers participated in a 3-week online training programme using iDECO, a bilingual web-based platform featuring authentic colposcopy cases, gamified learning pathways, and personalized analytics. The primary outcomes included colposcopy competence in general assessment, colposcopic findings, diagnostic accuracy, and management decisions. The secondary outcomes focused on participant feedback and satisfaction. Of 369 participants who completed pretests, 333 (90.24%) completed post-training assessments. Significant improvements were observed across all competency domains. Diagnostic accuracy increased with an odds ratio (OR) of 1.72 (95% CI: 1.60-1.86) with the greatest gains in high-grade lesion identification [OR = 2.27 (95% CI: 1.94-2.64)]. Squamocolumnar junction visibility and transformation zone type assessments improved with ORs of 1.41 (95% CI: 1.31-1.51) and 1.87 (95% CI: 1.73-2.01), respectively. Biopsy decision-making accuracy also showed significant improvement [OR = 2.09 (95% CI: 1.91-2.29)]. International participants showed lower baseline performance but achieved the greatest improvements. Greater than 85% of participants rated the training highly satisfactory and 83.56% preferred intelligent training over traditional methods. iDECO-based training significantly improved colposcopy competence across diverse international settings with high user satisfaction. These findings support the potential for worldwide implementation of intelligent digital training tools to address colposcopy training gaps and contribute to the elimination of cervical cancer.

The uterine cervix is a critical mucosal interface that balances immune defense and reproductive function, yet how its distinct epithelial compartments coordinate responses to infection remains unclear. Here, we integrate patient-derived three-dimensional cervical organoids, single-cell transcriptomics, and native tissue analysis to construct a high-resolution atlas of epithelial cell diversity and immune dynamics during Chlamydia trachomatis infection. We demonstrate that cervical organoids closely resemble native tissue at transcriptional and cellular levels, identifying epithelial subtypes with region-specific immune specializations. Upon infection, ectocervical epithelia reinforce barrier integrity, whereas endocervical epithelia, particularly uninfected bystander cells, exhibit extensive transcriptional reprogramming characterized by robust interferon activation, antigen presentation, and antimicrobial defense. Infection profoundly reshapes epithelial intercellular communication, positioning bystander cells as major contributors to signaling networks coordinating immune responses and tissue regeneration. Our findings highlight a sophisticated epithelial-intrinsic immune network critical for cervical mucosal defense and establish a physiologically relevant platform for studying host-pathogen interactions and guiding targeted mucosal therapies against reproductive tract infections and pathologies.

BackgroundCervical cancer (CC) is the fourth most frequent cancer and fourth leading cause of death in women. In 2020, 604 000 new cases and 342 000 deaths worldwide were estimated. According to the Global Cancer Observatory, the incidence of CC in Indonesia increased from 9.2% in 2020 to 16.8% in 2022. Obesity is associated with increased CC morbidities. A meta-analysis showed significant relationship between high BMI and elevated risk of developing female reproductive tumors, including cancer. This study aims to identify the association between BMI and CC and precancerous cervical lesions (PCL) in screened women.Material/MethodsThe study was conducted at Province General Hospital Margono, Indonesia, involving patients registered in 2022–2024 who had positive visual inspection with acetic acid test results and underwent the large loop excision of the transformation zone (LLETZ) procedure, with available histopathology results. Patients were classified into normal BMI and overweight/obesity BMI groups. Association between BMI and CC or PCL was analyzed.ResultsAnalysis of patients’ BMI with histopathologically confirmed CC and PCL vs those without showed 26 (41.3%) of 63 patients with abnormal BMI had CC or PCL. BMI was significantly related to occurrence of CC and PCL (OR 3.033; 95% CI 1.034–8.899; P=0.04), indicating patients with abnormal BMI have 3.033-fold higher risk of developing CC or PCL than those with normal BMI.ConclusionsObesity is an underrated risk factor in women with a higher-than-normal BMI to have increased probability of developing CC or PCL. Higher BMI worsens the progressivity of the disease and health burden.

Background: The limited self-repair capacity of nerve tissue requires a new therapeutic approach. Mesenchymal stem cells from the uterine cervix, hUCESC, have shown anti-inflammatory, regenerative, and anti-oxidative stress effects through their secretome, which makes them candidates to evaluate their potential in the context of neuronal damage. In this study, we aimed to determine whether secretome or conditioned medium of hUCESC (hUCESC-CM) has beneficial action in the treatment of PC-12 and HMC3 cells in vitro under conditions of oxidative stress and inflammation. Methods: Differentiated PC-12 cells and HMC3 cells were subjected to oxidative stress and inflammatory conditions in the presence of hUCESC-CM. The expression of factors related to both processes was evaluated by q-RT-PCR. Results: PC-12 cells treated with hUCESC-CM showed a significant increase in the expression of anti-oxidative stress factors (HO-1 and Nrf2) and a significant decrease in the expression of pro-inflammatory factors (IL1β, IL6 and TNFα). In addition, the treatment of HMC3 cells with hUCESC-CM significantly decreased the expression of IL6 and TNFα and enhanced the expression of neuroprotective factors such as BDNF and GDNF. Conclusions: Considering that both oxidative stress and inflammation are interrelated and implicated in several nerve injuries and neurodegenerative disorders, the effects of hUCESC-CM on neuronal cells are very promising.

154 Background: Cervical (CC), breast (BC), and colorectal (CRC) cancer screening rates lag for US Latinas compared to non-Latina white women. Obesity/overweight, a known cancer risk factor, is prevalent among Latinas, making cancer screening a pressing priority in this population. This study investigates determinants of CC, BC, and CRC screening adherence at baseline and screening uptake at study completion among overweight/obese Latinas in SANOS (Health and Nutrition for All), a 6-month culturally tailored lifestyle program with navigation to insurance, primary care, and screening. Methods: We enrolled 412 Spanish-speaking Latinas with BMI ≥25 kg/m 2 (2019-2024). Surveys conducted at baseline and study completion captured participants’ time in the US, English proficiency, primary care physician (PCP) access, health insurance status, and cancer screening adherence per USPSTF guidelines. Logistic regression assessed determinants of screening adherence, and Fisher’s exact tests compared screening uptake at study completion, with significance at p &lt; 0.05. Results: Of 412 participants (mean age 43.4 ± 9.7), 77.5% had limited English proficiency, and 39.9% were insured, mainly through Medicaid (73.0%). Baseline adherence was high for CC (75.7%; 311/411 eligible) and BC (66.5%; 165/248), while only 45.9% (68/148) for CRC. Logistic regression showed that more time living in the US (CRC: OR = 1.06, p = 0.001; BC: OR = 1.06, p &lt; 0.001), having insurance (CRC: OR = 2.97, p = 0.002; BC: OR = 2.26, p = 0.006), and more recent PCP access (CRC: OR = 0.08, p &lt; 0.001; BC: OR = 0.24, p &lt; 0.001) predicted CRC and BC adherence. Having insurance (OR = 1.76, p = 0.026) and more recent PCP access (OR = 0.24, p &lt; 0.001) predicted CC adherence. Participants reporting CC adherence were 13.3 (CI .95 = 5.38, 37.87) and 7.76 (CI .95 = 2.05, 50.87) times more likely to report BC and CRC adherence, respectively. At study completion, among those non-adherent at baseline, CRC uptake (13.6%, 9/66) was significantly lower than BC uptake (44.8%, 30/67; p &lt; 0.001) and CC uptake (35.8%, 24/67; p &lt; 0.018). Conclusions: High CC and BC screening adherence among overweight/obese Latinas demonstrates regular engagement with the healthcare system; however, disproportionately low CRC screening reflects a critical missed opportunity for prevention. Interventions to promote CRC screening adherence in this population should include both provider education and culturally tailored patient education on CRC risk and screening. Further research is needed on Latinas' perceived barriers to CRC screening and their awareness of screening options.

Background This study aimed to evaluate the effectiveness of endocervical curettage (ECC) in detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in HPV-positive postmenopausal women with a type 3 transformation zone (TZ3) and to identify additional predictive factors.MethodsA retrospective observational study was conducted including 137 HPV-positive postmenopausal women who underwent colposcopy, ECC, and subsequent LEEP. Variables analyzed included age group, HPV genotype (16/18 vs. non-16/18), transformation zone type, cytology results, and ECC findings. Univariate and multivariable logistic regression analyses were performed to identify predictors of CIN2 + confirmed by LEEP histology.ResultsCIN2 + prevalence was 27.7% (38/137); ≥CIN3 occurred in 26/137 (19.0%). In multivariable analysis, high-grade cytology (adjusted OR [aOR] 4.65; 95% CI 1.92–11.30; p < 0.001), TZ3 (aOR 3.05; 1.05–8.85; p = 0.040) and hrHPV non-16/18 (aOR 2.52; 1.08–5.90; p = 0.032) were independently associated with CIN2+, while age ≥ 51 years was not (aOR 1.28; 0.57–2.85; p = 0.55). Absolute risks of CIN2 + were 36.8% with non-16/18 vs. 16.4% with HPV16/18. ECC (cut-off CIN2+) yielded sensitivity 73.7%, specificity 77.8%, PPV 56.0% and NPV 88.5%. Conclusion In postmenopausal women with persistent hrHPV, high-grade cytology and TZ3 are the main drivers of CIN2+ risk. ECC is most useful as a rule-out test (high NPV), whereas expedited diagnostic-therapeutic LEEP may be considered when ASC-H/HSIL coexists with TZ3 in women without fertility desire. The association between non-16/18 genotypes and CIN2+ observed here warrants confirmation in larger multicentre cohorts.