Background: Recent studies have shown preliminary evidence that vaccination against human papillomavirus (HPV) could decrease the risk of persistent/recurrent HSIL in women treated for high-grade cervical intraepithelial lesion (HSIL). We aimed to determine the benefits of HPV vaccination in patients undergoing conization for HSIL in real-life conditions and evaluate vaccination compliance associated with different funding policies. Methods: From January 2013 to July 2018, 265 women underwent conization in our center. From January 2013 to July 2017, treated patients (n = 131) had to pay for the vaccine, whereas after July 2017 the vaccine was publicly funded and free for treated women (n = 134). Post-conization follow-up controls were scheduled every six months with a Pap smear, HPV testing, and a colposcopy. Results: 153 (57.7%) women accepted vaccination (vaccinated group), and 112 (42.3%) refused the vaccine (non-vaccinated group). Persistent/recurrent HSIL was less frequent in vaccinated than in non-vaccinated women (3.3% vs. 10.7%, p = 0.015). HPV vaccination was associated with a reduced risk of persistent/recurrent HSIL (OR 0.2, 95%CI: 0.1–0.7, p = 0.010). Vaccination compliance increased when the vaccine was publicly funded (from 35.9% [47/131] to 79.1% [106/134], p < 0.001). Conclusions: HPV vaccination in women undergoing conization is associated with a 4.5-fold reduction in the risk of persistent/recurrent HSIL. Vaccination policies have an important impact on vaccination compliance.

Human papillomavirus (HPV)-independent vulvar squamous cell carcinomas (VSCC) and its precursors frequently harbour TP53 mutations. Recently, six p53 immunohistochemical (IHC) patterns have been defined, which have shown strong correlation with TP53 mutation status. However, few studies have applied this new six-pattern framework and none of them exhaustively compared p53 IHC positivity and patterns between invasive VSCC and adjacent skin lesion. We performed p53 IHC in a series of 779 HPV-independent VSCC with adjacent skin and evaluated the IHC slides following the newly described classification. Some 74.1% invasive VSCC showed abnormal p53 IHC staining. A skin lesion was identified in 450 cases (57.8%), including 254 intraepithelial precursors and 196 inflammatory/reactive lesions. Two hundred and ten of 450 (47%) VSCC with associated skin lesions showed an abnormal p53 IHC stain, with an identical staining pattern between the VSCC and the adjacent skin lesion in 80% of the cases. A total of 144/450 (32%) VSCC showed wild-type p53 IHC both in the invasive VSCC and adjacent skin lesion. Finally, 96/450 (21%) VSCC showed p53 IHC abnormal staining in the invasive VSCC but a wild-type p53 staining in the skin lesion. Most of the discordant cases (70/96; 73%) showed adjacent inflammatory lesions. In conclusion, the p53 IHC staining and pattern are usually identical in the VSCC and the intraepithelial precursor.

Vulvar squamous cell carcinoma (VSCC) is a rare malignancy with dual pathogenesis, Human papillomavirus (HPV)-associated and HPV-independent, with a poorly explored molecular landscape. We aimed to summarize the findings of the series analyzing molecular hallmarks of this neoplasm. In January 2021, we conducted a comprehensive literature search using Pubmed Medline and Scopus to identify publications focused on genomic profiling of VSCC. Observational studies, including both prospective and retrospective designs, evaluating molecular alterations in VSCC were deemed eligible. A total of 14 studies analyzing 749 VSCC were identified. The study series were heterogeneous in HPV testing and sequencing strategies, included small sets of tumors and cancer genes, and commonly lacked survival analysis. Only one extensive targeted next-generation sequencing-based study comprised a large cohort of 280 VSCC. The mutated genes, their number, and frequencies were highly variable between the series. Overall, TP53 and CDKN2A, followed by PIK3CA, HRAS, and PTEN, were the most frequently studied and mutated genes. Mutations involved in the PI3K/AKT/mTOR pathway, including TP53, HRAS, KRAS, and PIK3CA, have been consistently reported across the studies. However, the role of individual mutations or pathways in the development of VSCC remains unclear. In conclusion, heterogeneity and the small sample size of available molecular series contribute to a limited view of the molecular landscape of VSCC. Large-scale genome- or exome-wide studies with robust HPV testing are necessary to improve the molecular characterization of VSCC.

(1) OBJECTIVE: To assess the performance of CA125, HE4, ROMA index and CPH-I index to preoperatively identify epithelial ovarian cancer (EOC) or metastatic cancer in the ovary (MCO). (2) METHODS: single center retrospective study, including women with a diagnosis of adnexal mass. We obtained the AUC, sensitivity, specificity and predictive values were of HE4, CA125, ROMA and CPH-I for the diagnosis of EOC and MCO. Subgroup analysis for women harboring adnexal masses with inconclusive diagnosis of malignancy by ultrasound features and Stage I EOC was performed. (3) RESULTS: 1071 patients were included, 852 (79.6%) presented benign/borderline tumors and 219 (20.4%) presented EOC/MCO. AUC for HE4 was higher than for CA125 (0.91 vs. 0.87). No differences were seen between AUC of ROMA and CPH-I, but they were both higher than HE4 AUC. None of the tumor markers alone achieved a sensitivity of 90%; HE4 was highly specific (93.5%). ROMA showed a sensitivity and specificity of 91.1% and 84.6% respectively, while CPH-I showed a sensitivity of 91.1% with 79.2% specificity. For patients with inconclusive diagnosis of malignancy by ultrasound features and with Stage I EOC, ROMA showed the best diagnostic performance (4) CONCLUSIONS: ROMA and CPH-I perform better than tumor markers alone to identify patients harboring EOC or MCO. They can be helpful to assess the risk of malignancy of adnexal masses, especially in cases where ultrasonographic diagnosis is challenging (stage I EOC, inconclusive diagnosis of malignancy by ultrasound features).

Purpose: Indocyanine green (ICG) is frequently used for the detection of the sentinel lymph node (SLN) in gynecology, but it carries the loss of the presurgical SLN mapping provided by [^99mTc]-based colloids. Hybrid tracers such as ICG-[^99mTc]Tc-albumin nanocolloid combine the benefits of both components. The aim of this study was to evaluate the feasibility and applicability of this hybrid tracer injected by transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR) approach in the detection of SLNs in patients with intermediate- and high-risk EC.Methods: Fifty-two patients with intermediate- and high-risk EC underwent SLN biopsy after injection of a hybrid tracer using the TUMIR approach, followed by pelvic and paraaortic lymphadenectomy. SLNs were detected preoperatively by lymphoscintigraphic study and intraoperatively by gamma probe and near-infrared (NIR) optical laparoscopic camera.Results: Preoperative lymphatic drainage was obtained in 69% and intraoperative detection in 71.4% of patients. A total of 146 SLNs (4.17 SLNs/patient) were biopsied. Pelvic bilateral detection was observed in 57% of the women and paraaortic drainage in 34% of the patients. The radioactive component allowed the detection of SLN in 97.1% of the patients, while the fluorescent component detected 80%. In more than 17% of the patients with intraoperative detection, SLNs were detected only by the radioactive signal. Lymph node metastasis was identified in 14.3% of patients submitted to SLNB. The sensitivity and negative predictive value for metastatic involvement were 100%.Conclusion: TUMIR injection of a hybrid tracer in patients with intermediate- and high-risk EC combines the benefits of the radiotracer and the fluorescence methods with a single tracer. The method increases the paraaortic detection rate and allows a potential increase in SLN detection. Notwithstanding, based on our findings, the radioactive component of the hybrid tracer cannot be obviated.

Recently published guidelines stratify the risk of high-grade squamous intraepithelial lesion/grade 3 cervical intraepithelial neoplasia (HSIL/CIN3) based on hrHPV detection and Pap smear results. However, colposcopic impression could also provide valuable information for risk estimation. We aimed to analyze the value of adding colposcopic impression to screening tests for the diagnosis of HSIL/CIN3 in 302 women referred for colposcopy due to an abnormal Pap smear. All women underwent hrHPV detection and genotyping (HPV 16/18 vs. non-16/18 hrHPV), Pap smear, and colposcopy with at least one biopsy. HSIL Pap smear, HPV 16/18, and grade 2 colposcopy findings increased the risk of HSIL/CIN3 in the univariate analysis but only colposcopy retained significance in the multivariate model. At least 30% of the women with grade 2 colposcopy findings had HSIL/CIN3, independent of the screening test results. Among women with an HSIL Pap smear and grade 2 colposcopy findings, 53.3% had HSIL/CIN3 independently of the hrHPV genotype. Contrarily, the prevalence of HSIL/CIN3 in women with <HSIL Pap smear, non-HPV 16/18 infection, and normal colposcopy or with grade 1 findings was 2.9% and 8.1%, respectively. In conclusion, colposcopy impression provides essential information to identify women at risk of HSIL/CIN3.