These guidelines are an update to the 2008 UK guidelines for the management of sexual and reproductive health of people living with HIV. The writing group has followed updated British Association for Sexual Health and HIV (BASHH) guideline methodology, notably using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system for assessing evidence and making recommendations. We have made significant changes to the recommendations which are summarised below.

BACKGROUND:DNA methylation has been proposed as a predictive biomarker. Cervical intraepithelial neoplasia grade 2 (CIN2) was historically the cut-off for surgical treatment, however it is increasingly managed with active surveillance, while there is currently no accurate way to predict which lesions will regress. METHODS:We performed the first Illumina 850k array on DNA from serial liquid based-cytology cervical samples from young women with CIN2 that were managed with active surveillance (n = 58). Linear regression identified differentially-methylated sites at baseline distinguishing regressors from non-regressors with persistent or progressive disease at 24-months. Associations with imminent regression and histological change were also evaluated. RESULTS:We identified three novel differentially-methylated sites; cg12754953 (ALDH9A1) methylation was significantly increased at baseline in non-regressors, cg18887759 (MED25) methylation was significantly lower in samples from women who regressed within the subsequent 12 months, and cg13556949 (TULP2) methylation increased over time between baseline and 12-months of follow-up in non-regressors as compared to regressors. CONCLUSION:Methylation could help guide treatment decisions in women considering active surveillance of CIN2 lesions. ALDH9A1, MED25 and TULP2 may be implicated as genes with possible roles in host response to viral mechanisms. Larger prospective studies are needed to validate these findings.

Multizonal anogenital intraepithelial neoplasia (MZIN) is an uncommon chronic pre-malignant condition. In the United Kingdom (UK) and elsewhere MZIN is managed by a variety of clinical specialities with differing strategies, resulting in a lack of standardisation in diagnosis and treatment which ultimately disadvantages those affected. Screening for anogenital precancerous conditions is sporadic rather than nationalised in the UK and elsewhere in Europe, with the exception of the cervix. To address this lack of standardisation, the BSCCP brought together a panel of stakeholders from aligned expert society committees (IANS, EFC and BSSVD) to review existing evidence and provide a framework for national UK guidelines. Here, we define terminology and scope, as a platform for subsequent guideline development and guide further research. We define MZIN as Human Papillomavirus (HPV)-related squamous intraepithelial lesions occurring in two or more anogenital regions. People with MZIN are a high-risk group for anogenital cancers and subsequently may require tailored monitoring in specialist multi-disciplinary clinics. Centralisation of care and education for primary care providers may improve management. The development of guidelines which incorporate all clinical stakeholders are now needed to provide an international framework regarding the screening, diagnosis, treatment and future prevention of MZIN.

Endometrial hyperplasia (EH) comprises a spectrum of abnormal proliferative changes in the endometrium, ranging from benign glandular overgrowth to lesions with substantial malignant potential. The importance of risk stratification and early identification is highlighted by the growing recognition of EH as a precursor to endometrial cancer. The main causes of EH, according to epidemiological research, include obesity, polycystic ovarian syndrome (PCOS), metabolic dysfunction, and extended exposure to unopposed estrogen. Emerging molecular markers, histological analysis, and imaging are all necessary for a proper diagnosis of EH because it might appear with vague clinical symptoms such as irregular uterine bleeding. Surgical intervention or progestin therapy are two possible management techniques for EH, depending on the lesion's intricacy and the patient's medical history, including fertility issues. Personalized therapy techniques and recent developments in molecular profiling have the potential to enhance patient outcomes by matching treatment to tumor biology and individual risk profiles. This review highlights the translational potential of molecular insights while synthesizing the most recent data on the epidemiology, risk factors, diagnostic techniques, and therapy of EH. A deeper comprehension of these elements is necessary to maximize treatment results and stop the development of endometrial cancer.

Human papillomavirus (HPV) is causally related to neoplasia in multiple anogenital zones including anal, vulval, vaginal, and cervical areas in women. Care for anogenital neoplasia involves multiple specialist fields. Women with a history of cervical neoplasia are at increased risk of multiple anogenital neoplasias and second cancers occur in the anogenital zones. Results of a survey on current management practices across Europe are presented. A questionnaire was developed by iterative process and circulated amongst specialists in all fields associated with anogenital neoplasia. Data was recorded and analysed using Microsoft Excel/Stata. 316/430 (73.5

Evidence on the diagnosis and management of women with primary lymphoma of the uterine cervix (PLUC) is limited. The present study performed a systematic review of the literature and provided an overview of the reported cases of PLUC. A total of 213 reports were included, which comprised 339 patients with PLUC. The mean age of the patients was 48.5 years (median, 46 years; age range, 15-88 years). The most common presenting symptom was vaginal bleeding (189/318, 59.4%) and its duration ranged from 4.5 days to 24 months, with only a small fraction of patients developing 'B' symptoms including weight loss, night sweats and fever (28/318, 8.8%). Biopsy (either excisional or punch biopsy) was the most commonly used initial/primary diagnostic modality (78/278, 28.1%) followed by ultrasound (59/278, 21.2%). The most common management approach out of 309 patients was surgery (with or without adjuvant or neo-adjuvant treatment; 115/309), followed by chemotherapy alone (109/309), which was followed by chemo-radiotherapy alone (62/309). The follow-up period for survivors ranged from 4 weeks to 246 months, and the absolute 5-year and 10-year survival rates were 86.1 and 85.4%, respectively. The relatively low number of patients and high heterogeneity did not permit a robust comparative analysis of the survival outcomes. However, the longest median survival was reported for women who received neo-adjuvant chemotherapy followed by surgery (15 patients; 72 months). Although malignant PLUC is rare, early detection, optimal therapeutic management, and multidisciplinary involvement of gynecologic oncologists and lymphoma specialists may offer benefit to patients diagnosed with this rare disease.

Histological diagnosis of cervical intraepithelial neoplasia grade 2 (CIN2) has traditionally been the cutoff for local surgical treatment, due to a substantial risk of cancer development. However, evidence from the past decade suggests 50-60% of CIN2 lesions spontaneously regress, and active surveillance (or conservative management-ie, leaving the lesion untreated) might be justified in some cases. Active surveillance of CIN2 lesions is now practised widely, although clear recommendations on eligibility, frequency of surveillance, threshold for treatment, and criteria for return to routine recall are insufficient in most countries. In 2023, the cumulative risk of invasive cancer over 20 years was found to be substantially higher in patients under active surveillance when compared with patients who received immediate local treatment, with the greatest difference observed in women older than 30 years. This Policy Review and practice algorithm from the British Society of Colposcopy and Cervical Pathology and the European Society of Gynaecologic Oncology prevention committees aims to review existing evidence and present clear recommendations to assist clinical decision making. Active surveillance, rather than immediate treatment, might be reasonable in a carefully selected cohort of patients. The risk of progression, need for repeat visits, and cumulative risk of future invasion associated with active surveillance should be carefully balanced against the benefits of awaiting regression, including consideration of the woman's age, fertility wishes, additional risk factors, and likelihood of compliance to follow-up. Clinical audit and, ideally, prospective databases are required to monitor long-term outcomes and safety.

ObjectiveTo compare the cost-effectiveness of different treatments for cervical intraepithelial neoplasia (CIN).DesignA cost-effectiveness analysis based on data available in the literature and expert opinion.SettingEngland.PopulationWomen treated for CIN.MethodsWe developed a decision-analytic model to simulate the clinical course of 1000 women who received local treatment for CIN and were followed up for 10 years after treatment. In the model we considered surgical complications as well as oncological and reproductive outcomes over the 10-year period. The costs calculated were those incurred by the National Health Service (NHS) of England.Main outcome measuresCost per one CIN2+ recurrence averted (oncological outcome); cost per one preterm birth averted (reproductive outcome); overall cost per one adverse oncological or reproductive outcome averted.ResultsFor young women of reproductive age, large loop excision of the transformation zone (LLETZ) was the most cost-effective treatment overall at all willingness-to-pay thresholds. For postmenopausal women, LLETZ remained the most cost-effective treatment up to a threshold of 31,500 pound, but laser conisation became the most cost-effective treatment above that threshold.ConclusionsLLETZ is the most cost-effective treatment for both younger and older women. However, for older women, more radical excision with laser conisation could also be considered if the NHS is willing to spend more than 31,500 pound to avert one CIN2+ recurrence.

Primary malignant melanoma (MM) of the cervix uteri is a rare and aggressive malignancy of the female reproductive tract. Considering that clinical data on this cancer are scarce, we aimed to comprehensively examine the currently available literature and provide an overview of the reported cases of cervical MM focusing on the clinical characteristics, diagnosis and therapeutic management. We conducted a systematic review of the literature by screening three electronic databases until June 2022. The critical appraisal checklist provided by the Joanna Briggs Institute was employed to evaluate the overall quality of the studies. We included 96 reports, which comprised 137 patients diagnosed with MM of the cervix. The mean age of the patients was 56.5 (median: 58, age range: 33-88). Data regarding menopausal status were provided for 98 patients with 15 being premenopausal and 83 being postmenopausal. The most common presenting symptom was vaginal bleeding (83%, 100/121). Biopsy (either excisional or punch biopsy) was used as the first diagnostic modality in most of the patients (67%, 64/95), followed by cytology (18%, 17/95). In 74 cases, the FIGO staging system for cervical cancer was used with the most common stage being FIGO stage I (38%, 28/74), followed by FIGO stage II (36%, 27/74), FIGO stage III (19%, 14/74) and FIGO stage IV (7%, 5/74). Most of the patients were managed surgically (90%, 119/131) with a hysterectomy (either radical or total), and a salpingo-oophorectomy with/without lymphadenectomy was the most common approach utilized (40%, 48/119). The data of clinical outcomes were provided for 105 patients, of whom 61 died (58%, 61/105) and 44 survived (42%, 44/105). Knowledge regarding the rare occurrence of MM in the cervix and the increased awareness of clinicians can prevent clinical misdiagnosis and ultimately improve further the clinical outcomes of patients developing this rare malignancy.

Background The trade-off between comparative effectiveness and reproductive morbidity of different treatment methods for cervical intraepithelial neoplasia (CIN) remains unclear. We aimed to determine the risks of treatment failure and preterm birth associated with various treatment techniques.Methods In this systematic review and network meta-analysis, we searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials database for randomised and non-randomised studies reporting on oncological or reproductive outcomes after CIN treatments from database inception until March 9, 2022, without language restrictions. We included studies of women with CIN, glandular intraepithelial neoplasia, or stage IA1 cervical cancer treated with excision (cold knife conisation [CKC], laser conisation, and large loop excision of the transformation zone [LLETZ]) or ablation (radical diathermy, laser ablation, cold coagulation, and cryotherapy). We excluded women treated with hysterectomy. The primary outcomes were any treatment failure (defined as any abnormal histology or cytology) and preterm birth (<37 weeks of gestation). The network for preterm birth also included women with untreated CIN (untreated colposcopy group). The main reference group was LLETZ for treatment failure and the untreated colposcopy group for preterm birth. For randomised controlled trials, we extracted group-level summary data, and for observational studies, we extracted relative treatment effect estimates adjusted for potential confounders, when available, and we did random-effects network meta-analyses to obtain odds ratios (ORs) with 95% CIs. We assessed within-study and across-study risk of bias using Cochrane tools. This systematic review is registered with PROSPERO, CRD42018115495 and CRD42018115508.Findings 7880 potential citations were identified for the outcome of treatment failure and 4107 for the outcome of preterm birth. After screening and removal of duplicates, the network for treatment failure included 19 240 participants across 71 studies (25 randomised) and the network for preterm birth included 68 817 participants across 29 studies (two randomised). Compared with LLETZ, risk of treatment failure was reduced for other excisional methods (laser conisation: OR 0middot59 [95% CI 0middot44-0middot79] and CKC: 0middot63 [0middot50-0middot81]) and increased for laser ablation (1middot69 [1middot27-2middot24]) and cryotherapy (1middot84 [1middot33-2middot56]). No differences were found for the comparison of cold coagulation versus LLETZ (1middot09 [0middot68-1middot74]) but direct data were based on two small studies only. Compared with the untreated colposcopy group, risk of preterm birth was increased for all excisional techniques (CKC: 2middot27 [1middot70-3middot02]; laser conisation: 1middot77 [1middot29-2middot43]; and LLETZ: 1middot37 [1middot16-1middot62]), whereas no differences were found for ablative methods (laser ablation: 1middot05 [0middot78-1middot41]; cryotherapy: 1middot01 [0middot35-2middot92]; and cold coagulation: 0middot67 [0middot02-29middot15]). The evidence was based mostly on observational studies with their inherent risks of bias, and the credibility of many comparisons was low.Interpretation More radical excisional techniques reduce the risk of treatment failure but increase the risk of subsequent preterm birth. Although there is uncertainty, ablative treatments probably do not increase risk of preterm birth, but are associated with higher failure rates than excisional techniques. Although we found LLETZ to have balanced effectiveness and reproductive morbidity, treatment choice should rely on a woman's age, size and location of lesion, and future family planning.