Mario Preti

Oncolytic Viruses in Ovarian Cancer: Where Do We Stand? A Narrative Review

Ovarian cancer (OC) remains the most lethal gynecologic malignancy with limited effective treatment options. Oncolytic viruses (OVs) have emerged as a promising therapeutic approach for cancer treatment, capable of selectively infecting and lysing cancer cells while stimulating anti-tumor immune responses. Preclinical studies have demonstrated significant tumor regression and prolonged survival in OC models using various OVs, such as herpes simplex. Early-phase clinical trials have shown a favorable safety profile, though the impact on patient survival has been modest. Current research focuses on combining OVs with other treatments like immune checkpoint inhibitors to enhance their efficacy. We provide a comprehensive overview of the current understanding and future directions for utilizing OVs in the management of OC.

Link between isolated para-aortic lymph node metastasis and intrauterine cancer site in early stage endometrial cancer

Missing occult para-aortic lymph node metastasis is one of the primary concerns of sentinel lymph node biopsy in endometrial cancer. Our study aimed to evaluate the relationship between intrauterine cancer site and isolated para-aortic lymph node metastasis to tailor treatment and reduce the false negative rate of the sentinel lymph node procedure. A retrospective, multicenter, case control study was performed in four international centers. All patients with positive lymph nodes who had complete surgical staging with pelvic and para-aortic lymphadenectomy, between January 2013 and December 2023, were included. Detailed descriptions of the cancer location within the uterine cavity on the cranio-caudal plane and the myometrial wall involvement on the cranio-caudal and ventro-dorsal planes were collected, as were clinical data and cancer histological features. Patients with isolated para-aortic lymph node metastasis were allocated to group 1; patients with pelvic lymph node metastasis and those with both pelvic and para-aortic lymph node metastasis were allocated to group 2. The groups were compared according to the variables collected. 200 preoperative early stage endometrial cancer patients with postoperative International Federation of Gynecology and Obstetrics 2009/2023 stage IIIC1/IIIC2 were included in our study: 42 patients (21%) with isolated para-aortic lymph node metastasis were allocated to group 1 and the remaining patients to group 2. The two groups had comparable clinical and pathological characteristics (p>0.05): mean age was 66.5±10.3 (group 1) and 63.5±11.9 (group 2); endometrioid histotype was the predominant one for both groups (50%); most patients had myometrial infiltration >50% (80.9% and 79.7%), grade 3 (61.9% and 63.9%), and lymph vascular space invasion (78.5% and 82.2%). Cancers involving the fundal uterine cavity, the fundal myometrial wall, or the anterior myometrial wall were 3.11 (1.04-9.27), 3.03 (1.12-8.21), and 2.12 (0.77-5.80) times more likely to metastasize only to para-aortic lymph nodes compared with cancers located in other uterine sites. In this study, the intrauterine location of the cancer determined the site of lymph node metastasis. When the tumor involved the fundus (cavity or wall) and infiltrated exclusively the anterior wall, the baseline risk of spreading only into the para-aortic area increased significantly in selected patients at risk of nodal disease.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) consensus statement on the management of vaginal intraepithelial neoplasia

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) developed consensus statements on pre-invasive vulvar lesions in order to improve the quality of care for patients with vaginal intraepithelial neoplasia (VaIN). The management of VaIN varies according to the grade of the lesion: VaIN 1 (low grade vaginal squamous intraepithelial lesions (SIL)) can be subjected to follow-up, while VaIN 2-3 (high-grade vaginal SIL) should be treated. Treatment needs individualization according to the patient's characteristics, disease extension and previous therapeutic procedures. Surgical excision is the mainstay of treatment and should be performed if invasion cannot be excluded. Total vaginectomy is used only in highly selected cases of extensive and persistent disease. Carbon dioxide (CO

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) Consensus Statement on the Management of Vaginal Intraepithelial Neoplasia

Abstract The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) developed consensus statements on pre-invasive vulvar lesions in order to improve the quality of care for patients with vaginal intraepithelial neoplasia (VaIN). The management of VaIN varies according to the grade of the lesion: VaIN 1 (low grade vaginal squamous intraepithelial lesions (SIL)) can be subjected to follow-up, while VaIN 2–3 (high-grade vaginal SIL) should be treated. Treatment needs individualization according to the patient’s characteristics, disease extension and previous therapeutic procedures. Surgical excision is the mainstay of treatment and should be performed if invasion cannot be excluded. Total vaginectomy is used only in highly selected cases of extensive and persistent disease. Carbon dioxide (CO2) laser may be used as both an ablation method and an excisional one. Reported cure rates after laser excision and laser ablation are similar. Topical agents are useful for persistent, multifocal lesions or for patients who cannot undergo surgical treatment. Imiquimod was associated with the lowest recurrence rate, highest human papillomavirus (HPV) clearance, and can be considered the best topical approach. Trichloroacetic acid and 5-fluorouracil are historical options and should be discouraged. For VaIN after hysterectomy for cervical intraepithelial neoplasia (CIN) 3, laser vaporization and topical agents are not the best options, since they cannot reach epithelium buried in the vaginal scar. In these cases surgical options are preferable. Brachytherapy has a high overall success rate but due to late side effects should be reserved for poor surgical candidates, having multifocal disease, and with failed prior treatments. VaIN tends to recur and ensuring patient adherence to close follow-up visits is of the utmost importance. The first evaluation should be performed at 6 months with cytology and an HPV test during 2 years and annually thereafter. The implementation of vaccination against HPV infection is expected to contribute to the prevention of VaIN and thus cancer of the vagina. The effects of treatment can have an impact on quality of life and result in psychological and psychosexual issues which should be addressed. Patients with VaIN need clear and up-to-date information on a range of treatment options including risks and benefits, as well as the need for follow-up and the risk of recurrence.

Differentiated vulvar intraepithelial neoplasia long‐term follow up and prognostic factors: An analysis of a large historical cohort

AbstractIntroductionDifferentiated vulvar intraepithelial neoplasia (dVIN) is a high‐risk preinvasive vulvar lesion and precursor of human papillomavirus‐independent vulvar squamous cell carcinoma (VSCC). Due to its rarity, literature data on its malignant potential are scant. The aim of the study is to assess the risk of developing VSCC in patients surgically treated for dVIN not associated with VSCC (solitary dVIN) and the risk of VSCC recurrence in patients treated for dVIN associated with VSCC (dVIN‐VSCC) at first diagnosis.Material and methodsA historical cohort study was performed in a northern Italy referral center for vulvar neoplasms. All consecutive women surgically treated for histologically confirmed dVIN from 1994 to 2021 were collected. Primary outcome was cancer risk or recurrent cancer risk, secondary outcomes were risk factors associated with VSCC development or recurrence. Kaplan–Meier method and log‐rank test were used to estimate cancer risk or recurrent cancer risk differences and uni‐ and multivariate Cox regression analyses to identify risk factors associated with VSCC development in solitary dVIN and recurrence of dVIN‐VSCC.ResultsSeventy‐six patients with dVIN at preoperative biopsy were included: at excisional specimens 44 were solitary dVIN and 32 were dVIN‐VSCC. The absolute risk of VSCC development after solitary dVIN treatment was 43.2% with median time to to VSCC diagnosis of 25.4 months (range 3.5–128.0 months). VSCC recurrence absolute risk in treated dVIN‐VSCC patients was 31.3% with median time to VSCC recurrence of 52.9 months (range 6.5–94.8 months). At uni‐ and multivariate regression analyses, only compliant topical ultrapotent corticosteroid treatment after solitary dVIN excision showed an ability to prevent VSCC development. No protective effect by corticosteroid treatment was shown for VSCC recurrence in dVIN‐VSCC patients. Smoking was associated with higher cancer recurrence risk in dVIN‐VSCC patients on both uni‐ and multivariate regression analyses.ConclusionsPatients with dVIN have a high risk of developing both primary and recurring VSCC. Early recognition, long‐term follow up, and compliant ultrapotent topical corticosteroid treatment are recommended.

Is There a Place for Immune Checkpoint Inhibitors in Vulvar Neoplasms? A State of the Art Review

Vulvar cancer (VC) is a rare neoplasm, usually arising in postmenopausal women, although human papilloma virus (HPV)-associated VC usually develop in younger women. Incidences of VCs are rising in many countries. Surgery is the cornerstone of early-stage VC management, whereas therapies for advanced VC are multimodal and not standardized, combining chemotherapy and radiotherapy to avoid exenterative surgery. Randomized controlled trials (RCTs) are scarce due to the rarity of the disease and prognosis has not improved. Hence, new therapies are needed to improve the outcomes of these patients. In recent years, improved knowledge regarding the crosstalk between neoplastic and tumor cells has allowed researchers to develop a novel therapeutic approach exploiting these molecular interactions. Both the innate and adaptive immune systems play a key role in anti-tumor immunesurveillance. Immune checkpoint inhibitors (ICIs) have demonstrated efficacy in multiple tumor types, improving survival rates and disease outcomes. In some gynecologic cancers (e.g., cervical cancer), many studies are showing promising results and a growing interest is emerging about the potential use of ICIs in VC. The aim of this manuscript is to summarize the latest developments in the field of VC immunoncology, to present the role of state-of-the-art ICIs in VC management and to discuss new potential immunotherapeutic approaches.

Vulvar inspection at the time of cervical cancer screening: European Society of Gynaecological Oncology (ESGO), International Society for the Study of Vulvovaginal Disease (ISSVD), European College for the Study of Vulval Disease (ECSVD), and European Federation for Colposcopy (EFC) consensus statements

Vulvar squamous cell carcinoma incidence is increasing, especially among women under 60, largely attributed to human papillomavirus infections. Precursor pre-invasive vulvar lesions are frequently underdiagnosed. Routine vulvar inspection during cervical cancer screening could offer an opportunity for the detection of these lesions. To emphasize the importance of integrating routine vulvar inspection during cervical cancer screening procedures and to raise awareness about the early detection of vulvar squamous cell carcinoma and its precursors to reduce the diagnostic delay of vulvar pathologies. A multidisciplinary task force comprising experts from 4 international scientific societies was formed. A focused literature review was conducted, and consensus statements were developed through a structured voting process to ensure clinical relevance and comprehensiveness. The consensus defines key elements of normal vulvar anatomy, identifies potential pre-cancerous dermatoses, and highlights risk factors for vulvar malignancy. The consensus statements promote the integration of vulvar inspection into cervical cancer screening procedures, urging health care professionals across various levels to receive training and guidance in vulvar examinations and enhancing patient education. Health care providers are recommended to gather a brief history of vulvar symptoms, conduct comprehensive inspections of the vulvar area, and report any abnormalities. For patients with positive human papillomavirus or Pap tests, they should closely monitor vulvar findings, encourage self-examinations, and discuss risks for intra-epithelial or invasive neoplasia. Establishing standardized practices in vulvar inspection during cervical cancer screening procedures along with public awareness, could significantly impact early detection and timely interventions of vulvar pathologies at cancer risk ultimately reducing the burden of vulvar cancers.

Uterine smooth muscle tumors: a multicenter, retrospective, comparative study of clinical and ultrasound features

To evaluate a wide range of clinical and ultrasound characteristics of different uterine smooth muscle tumors to identify features capable of discriminating between these types. This was a retrospective, multicenter study that included 285 patients diagnosed with uterine smooth muscle tumors (50 leiomyosarcomas, 35 smooth muscle tumors of uncertain malignant potential, and 200 leiomyomas). The patients were divided into three groups based on the histological type of their tumors, and the groups were compared according to the variables collected. Leiomyosarcomas were more common in older and post-menopausal women. Compared with leiomyomas, smooth muscle tumors of uncertain malignant potential and leiomyosarcomas had similar ultrasound features such as absence of normal myometrium, multilocular appearance, hyper-echogenicity in case of uniform echogenicity, absence of posterior shadows, echogenic areas, and hyperechoic rim. Leiomyosarcomas were larger, had more cystic areas, and were associated with a higher prevalence of pelvic free fluid. Smooth muscle tumors of uncertain malignant potential were characterized by a higher frequency of International Federation of Gynecology and Obstetrics (FIGO) type 6-7, the absence of internal shadows, and, in the case of cystic area, the presence of a regular internal wall. Tumor outline varied among the three histological types. A color score of 1 was typical of leiomyoma, a color score 2 was mainly observed in leiomyomas and smooth muscle tumors of uncertain malignant potential, a color score 3 did not differ among the tumors, while a color of score 4 was related to leiomyosarcomas. When combining color scores 3 and 4, leiomyosarcomas and smooth muscle tumors of uncertain malignant potential showed a high percentage of both circumferential and intra-lesional vascularization. A cooked appearance was not statistically different among the tumors. Based on our findings, specific ultrasonographic features as well as age and menopausal status are associated with different uterine smooth muscle tumor types. Integration of these data can help the pre-operative assessment of these lesions for proper management.