Vaginosonography versus MRI in Pre-Treatment Evaluation of Early-Stage Cervical Cancer: An Old Tool for a New Precision Approach?

This study aims to analyze the sensitivity of vaginosonography (VGS) and magnetic resonance imaging (MRI) in the preoperative local evaluation of early-stage cervical cancers and to assess their accuracy in the detection of tumors, size of the lesions and stromal invasion by comparing them with the final histopathology report. This single-center study included 56 consecutive patients with cervical cancer who underwent VGS and MRI from November 2012 to January 2021. VGS significantly overestimated the lesion size by 2.7 mm (p = 0.002), and MRI underestimated it by 1.9 mm (p = 0.11). Both MRI and VGS had a good concordance with the pathology report (Cohen's kappa of 0.73 and 0.81, respectively). However, MRI had a false-negative rate (38.1%) that was greater than VGS (0%) in cases of cervical tumor size <2 cm. We found a good concordance between histology and VGS in the stromal infiltration assessment, with 89% sensitivity (95% CI 0.44−0.83) and 89% specificity (95% CI 0.52−0.86). VGS is a simple, inexpensive, widely available, and fast execution method that can complement ultrasound in particular cases and show a good correlation with MRI in the assessment of tumor dimensions, with a better performance in detecting small tumors (<2 cm).

SIIV position paper: clinical approach to vulval diseases. Need for quality standards.

This paper summarizes the position of the Italian Society of Vulvology on the clinical approach to vulval disease. A thorough history (general medical, gynaecological, and vulval history) is essential for a successful and fruitful vulvological examination. Characteristics of pruritus (itch) and pain, that are the two main vulval symptoms, should be collected and reported with precision, according to duration, temporal course, location, provocation, and intensity. Physical examination must consider both the general condition of the patient and the specific vulval region, that must be examined following a standardized methodology. The physical examination of the vulva is carried out with naked eye and adequate natural or halogen lighting. The subsequent use of instrumental magnification can be considered on particular parts of skin/mucosa, already highlighted with the first inspection. Also, palpation is essential, allowing to appreciate physical features of vulval lesions: consistency, surface, soreness, adherence to underlying plans. Finally, the five-step approach of the International Society for the Study of Vulvo-vaginal Disease about Terminology and Classification of Vulvar Dermatological Disorders (2012) is summarized. A vulval biopsy may be useful in the following situations: when clinical diagnosis is uncertain, lesion not responding to treatment; histologic confirmation for a clinical diagnosis and exclusion or confirmation of a suspected neoplastic intraepithelial or invasive pathology.

The Potential Impact of High-Risk Human Papillomavirus-Negative Cervical Intraepithelial Neoplasia 2+ on Primary Human Papillomavirus Screening.

OBJECTIVES: To investigate the prevalence of high-risk human papillomavirus (HPV)-negative cervical intraepithelial neoplasia (CIN) and invasive cervical carcinoma (ICC) and to analyze the distribution of other genotypes in this subset. METHODS: In total, 431 women who underwent excisional surgical treatment for CIN or ICC at the European Institute of Oncology, Milan, Italy, from January 2016 to December 2017 were retrospectively analyzed. The Linear Array HPV genotyping test (Roche Diagnostics) was performed on a postaliquot from high-risk-HPV-negative liquid-based cervical specimens, when available. Patient characteristics and the prevalence of high-risk-HPV-negative CIN grade 2 or worse (CIN2+) were tabulated. We used t tests to compare age between high-risk-HPV-positive and high-risk-HPV-negative patients. RESULTS: Overall, 8.9% of CIN2+ and 7.5% of ICC cases were high-risk HPV negative. There was no age difference between high-risk-HPV-negative CIN2+ women (mean [SD], 41.3 [8.7] years) and high-risk-HPV-positive women (mean [SD], 39.5 [9.0] years) (P = .28). The Linear Array result was available in 22 cases. Most high-risk-HPV-negative patients were positive for a single other genotype infection (32.6%). HPV 73 was the most prevalent genotype, followed by HPV 53 and HPV 84. HPV 26 was detected in 1 case of ICC. CONCLUSIONS: Our results showed a not-negligible proportion of high-risk-HPV-negative CIN2+, suggesting that cotesting would not miss these cases.

Borderline ovarian tumor in pregnancy: can surgery wait? A case series.

PURPOSE: To study the characteristics of borderline tumors (BOT) diagnosed during pregnancy, as either first diagnosis or relapse, to evaluate safety of expectant management. METHODS: 15 women affected by BOT during pregnancy were included, to evaluate clinical and histo-pathological characteristics. Age of patient, parity, gestational age, follow-up time, size of tumor, surgical approach, type and timing of surgery, FIGO stage, and histologic type were obtained through retrospective review. RESULTS: All patients except one were diagnosed with serous BOT (BOTs). Median follow-up time was 147 ± 57 months. Eight women received first diagnosis of BOT and seven had diagnosis of BOT recurrence during pregnancy, including three with a second relapse and four with a third relapse. BOT were diagnosed at FIGO stage I in most patients (75%) of the first group and in 14.3% of the second group, respectively. Micropapillary pattern was present in 71.4% of patients with first diagnosis of BOT, but only in 14.2% in case of relapse. All relapses were BOTs. No patient with BOT and concomitant pregnancy developed an invasive recurrence later. Overall, 24 relapses occurred in 10 patients (66.7%). Altogether 24 pregnancies occurred during follow-up, with a high livebirth rate (91.6%) and only 2 spontaneous miscarriages. CONCLUSION: According to our experience, an "expectation management" could be a safe option in case of both relapse of BOTs during pregnancy and first suspicion of BOT in pregnant women at advanced gestational age.

[HPV vaccination: not only female adolescents and not only prophylactic. Review and position paper of the Italian HPV Study Group (IHSG)].

HPV vaccination has been introduced in clinical practice in recent years and represents the most effective strategy of primary prevention of cervical carcinoma and of female genital preneoplastic conditions. One of the major issues of the subject is represented by vaccination coverage of the target population. Since its introduction, HPV vaccine efficacy has been progressively demonstrated also towards extragenital HPV-correlated conditions and in males too. Moreover, even subjects of older age groups or subjects who already had HPV infections have been demonstrated to received benefits from vaccination, due to improvements of their immunological response. Recently, vaccine efficacy has also been investigated in terms of adjuvant administration after treatments of preneoplastic or benign conditions of the female lower genital tract caused by HPVs; preliminary results indicate an interesting and promising field of application. On this basis, in this article an analysis of the state of the art has been performed, with specific regard to the Italian scenario and with the focus of future perspectives of implementation of the HPV vaccination policy. From the available evidences, the Italian HPV Study Group recommends the extension of systematic HPV vaccination to males too, to adult subjects and also after conservative treatment of genital HPV correlated conditions.

Human Papillomavirus Genotyping Compared With a Qualitative High-Risk Human Papillomavirus Test After Treatment of High-Grade Cervical Intraepithelial Neoplasia: A Systematic Review.

OBJECTIVE: To systematically examine human papillomavirus (HPV) genotyping compared with qualitative high-risk HPV result during follow-up after treatment of high-grade cervical intraepithelial neoplasia (CIN), for risk estimation of posttreatment high-grade CIN. DATA SOURCES: MEDLINE, Cochrane, and ClinicalTrials.gov were searched from January 2000 to April 2019 for prospective studies of women and retrospective studies of residual specimens from women, tested using HPV assays with genotype reporting. METHODS OF STUDY SELECTION: The primary outcome was posttreatment high-grade CIN after treatment of high-grade CIN. Risk of bias (individual study quality) was evaluated with a modified Newcastle-Ottawa Scale. Overall quality of evidence for the risk estimate outcomes was evaluated using modified GRADE methodology for observational diagnostic studies. TABULATION, INTEGRATION, AND RESULTS: Of the 233 identified abstracts, 33 full-text articles were retrieved, and seven studies were included in the synthesis. The risk of bias was deemed to be low. Either a positive qualitative HPV test result or a positive test result for the same genotype that was present pretreatment have a sensitivity for predicting posttreatment high-grade CIN that approaches 100%. However, the positive predictive value (PPV) for the same genotype result pretreatment and posttreatment (median 44.4%) is about double the PPV (median 22.2%) for qualitative HPV results. The PPV of a new HPV infection posttreatment approximates zero. Human papillomavirus genotyping discriminated risk of posttreatment high-grade CIN to a clinically significant degree for women after treatment procedures for high-grade CIN lesions, when same-genotype persistence was compared with new genotype infection. CONCLUSION: There is moderately high-quality evidence to support the improved clinical utility of HPV genotyping compared with qualitative HPV positivity to follow-up after treatment of high-grade CIN. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD42018091095. FUNDING SOURCE: Becton, Dickinson and Company, BD Life Sciences-Diagnostic Systems.

How to Address Sexual Problems in Female Cancer Patients.

Sexual health is an important aspect of human life, and cancer does not (and should not) change that. Data suggest that issues related to sexual function are quite common among women treated for cancer. However, clinicians often spend little to no time on the topic. This article provides a concise summary on the importance of sexual health among women treated for cancer, as well as an approach that general cancer clinicians can adopt in order to normalize sexual health issues for their patients. Finally, we provide an overview of sexual health therapeutics available in the United States and in Europe.

VIN usual type-from the past to the future.

Usual vulvar intraepithelial neoplasia (uVIN) is the most common VIN type, generally related to a human papillomavirus (HPV) infection, predominantly type 16. The incidence of uVIN has been increasing over the last decades, and a bimodal peak is observed at the age of 40-44 and over 55 years. Almost 40% of patients with uVIN have a past, concomitant or future HPV-associated lesion of the lower genital tract. HPV-related malignancies are associated with a persistent HPV infection. The host immune response is of crucial importance in determining clearance or persistence of both HPV infections and HPV-related VIN. About 60% of the patients present with symptoms. Clinical features of uVIN vary in site, number, size, shape, colour, and thickness of lesions. Multicentric disease is often present. Most uVIN lesions are positive at immunohistochemistry to p16(ink4a) and p14(arf), but negative to p53. Irrespective of surgical treatment used, uVIN recurrence rates are high. Positive margins do not predict the development of invasive disease and the need to re-excide the tissue around the scare remains to be demonstrated. Therefore, considering the low progression rate of uVIN and psycosexual sequelae, treatments should be as conservative as possible. Medical treatments available are mainly based on immunotherapy to induce normalisation of immune cell count in uVIN. None are approved by the food and drug administration (FDA) for the treatment of uVIN. If medical treatment is performed, adequate biopsies are required to reduce the risk of unrecognised invasive disease. Some studies suggest that failure to respond to immunotherapy might be related to a local immunosuppressive microenvironment, but knowledge of the uVIN microenvironment is limited. Moreover, our knowledge of the potential mechanisms involved in the escape of HPV-induced lesions from the immune system has many gaps. HPV vaccines have been demonstrated to be effective in preventing uVIN, with 94.9% efficacy in the HPV-naive population, while studies on therapeutic vaccines are limited. The low incidence of VIN requires large multicentre studies to determine the best way to manage affected patients and to investigate the immunological characteristics of the 'vulvar microenviroment' which leads to the persistence of HPV.