Background:
Patients with multiple sclerosis (MS) are at increased risk of infection. Vaccination can mitigate these risks but only if safe and effective in MS patients, including those taking ...disease-modifying drugs.
Methods:
A modified Delphi consensus process (October 2017–June 2018) was used to develop clinically relevant recommendations for making decisions about vaccinations in patients with MS. A series of statements and recommendations regarding the efficacy, safety and timing of vaccine administration in patients with MS were generated in April 2018 by a panel of experts based on a review of the published literature performed in October 2017.
Results:
Recommendations include the need for an ‘infectious diseases card’ of each patient’s infectious and immunisation history at diagnosis in order to exclude and eventually treat latent infections. We suggest the implementation of the locally recommended vaccinations, if possible at MS diagnosis, otherwise with vaccination timing tailored to the planned/current MS treatment, and yearly administration of the seasonal influenza vaccine regardless of the treatment received.
Conclusion:
Patients with MS should be vaccinated with careful consideration of risks and benefits. However, there is an urgent need for more research into vaccinations in patients with MS to guide evidence-based decision making.
The risk of infection associated with immunomodulatory or immunosuppressive disease-modifying drugs (DMDs) in patients with multiple sclerosis (MS) has been increasingly addressed in recent ...scientific literature. A modified Delphi consensus process was conducted to develop clinically relevant, evidence-based recommendations to assist physicians with decision-making in relation to the risks of a wide range of infections associated with different DMDs in patients with MS. The current consensus statements, developed by a panel of experts (neurologists, infectious disease specialists, a gynaecologist and a neuroradiologist), address the risk of iatrogenic infections (opportunistic infections, including herpes and cryptococcal infections, candidiasis and listeria; progressive multifocal leukoencephalopathy; human papillomavirus and urinary tract infections; respiratory tract infections and tuberculosis; hepatitis and gastrointestinal infections) in patients with MS treated with different DMDs, as well as prevention strategies and surveillance strategies for the early identification of infections. In the discussion, more recent data emerged in the literature were taken into consideration. Recommended risk reduction and management strategies for infections include screening at diagnosis and before starting a new DMD, prophylaxis where appropriate, monitoring and early diagnosis.
The World Health Organization (WHO) set the goal of 90% HPV vaccination coverage in the population to eliminate cervical cancer. Opportunistic vaccination is performed outside the free vaccination or ...catch-up programs. Both free and opportunistic HPV vaccination programs experienced slowdowns during the COVID-19 pandemic. In this retrospective study, we aimed to identify the benefits and the obstacles of opportunistic vaccination among male and female individuals who took advantage of the “on-demand” service offered by San Raffaele Hospital in Milan from April 2018 to May 2023. The impact that the COVID-19 pandemic had on vaccination adherence was also analyzed. Data on a total of 527 subjects were collected from an in-house database and through personal interviews. Women in the cohort of older patients (over 25) adhered to the vaccination schedule more than younger women. Opportunistic vaccination request is influenced by the need of a gynecologist, a general practitioner, or public health clinic availability. Women also showed good adherence to screening, demonstrating awareness of the importance of cervical cancer secondary prevention despite vaccination. Opportunistic vaccination offers the possibility of including individuals excluded from the free vaccination campaigns, often already affected by lesions caused by HPV, providing increased viral clearance and faster lesion regression. The main limit remains the economic burden.
It is unknown whether human papillomavirus (HPV) status impacts the prognosis of early stage cervical glandular lesions. This study assessed the recurrence and survival rates of in situ/microinvasive ...adenocarcinomas (AC) according to HPV status during a 5-year follow-up. The data were retrospectively analyzed in women with available HPV testing before treatment. One hundred and forty-eight consecutive women were analyzed. The number of HPV-negative cases was 24 (16.2%). The survival rate was 100% in all participants. The recurrence rate was 7.4% (11 cases, including four invasive lesions (2.7%)). Cox proportional hazards regression showed no difference in recurrence rate between HPV-positive and HPV-negative cases (
= 0.148). HPV genotyping, available for 76 women and including 9/11 recurrences, showed a higher relapse rate for HPV-18 than HPV-45 and HPV-16 (28.5%, 16.6%, and 9.52%,
= 0.046). In addition, 60% and 75% of in situ and invasive recurrences, respectively, were HPV-18 related. The present study showed that most ACs were positive for high-risk HPV, and the recurrence rate was unaffected by HPV status. More extensive studies could help evaluate whether HPV genotyping may be considered for recurrence risk stratification in HPV-positive cases.
Since the introduction of biomolecular testing for the identification of high-risk human papillomavirus DNA (hrHPV-DNA) in cervical cancer preventive strategies, many interesting aspects have emerged ...in this field; firstly, HPV-DNA testing has been demonstrated to have better sensitivity than conventional cytology in several settings: screening, triage of ASC-US and in follow-up after treatment. Despite this, some limitations of these new technologies have also been underlined: the major issue is the low specificity of the tests, which cannot discriminate between regressive and progressive infections. Thus, recent research has moved the attention towards novel markers of progression that could more precisely detect cases at real risk of cancer development. In view of the fact that progression to cancer is dependable of the E6/E7 proteins integration and transforming action, the overexpression of E6/E7 transcripts has been seen as a valuable marker of this risk. This review aims to summarise the literature data on this topic and to provide a clear view of the emerging perspectives.
The present study aimed to assess long-term follow-up outcomes in women with in situ/microinvasive adenocarcinoma (AC) of the uterine cervix treated conservatively.
Retrospective multi-institutional ...study including women with early glandular lesions and 5-year follow-up undergoing fertility-sparing treatment. Independent variables associated with recurrence were evaluated. Logistic regression analysis and Kaplan-Meier survival analysis with Logrank test were performed.
Of 269 women diagnosed with in situ/microinvasive AC, 127 participants underwent conservative treatment. During follow-up, recurrences were found in nine women (7.1%). The only factor associated with recurrence during follow-up was positive high-risk Human Papillomavirus (hr-HPV) testing (odds ratio 6.21, confidence interval 1.47-26.08,
= 0.012). HPV positivity in follow-up showed a recurrence rate of 21.7% against 3.8% in patients who were HPV-negative (
= 0.002, Logrank test). Among women with negative high-risk HPV tests in follow-up, recurrences occurred in 20.0% of non-usual-type histology vs. 2.1% of usual-type cases (
= 0.005).
HPV testing in follow-up is of pivotal importance in women with early glandular lesions undergoing conservative treatment, given its recurrence predictive value. However, women who are high-risk HPV-negative in follow-up with non-usual-type histopathology may represent a sub-population at increased risk of recurrences. Further studies should confirm these findings.
Quality Control (QC) and Quality Assurance (QA) principles are essential for effective cervical cancer prevention. Being a crucial diagnostic step, colposcopy's sensitivity and specificity ...improvements are strongly advocated worldwide since inter- and intra-observer differences are the main limiting factors. The objective of the present study was the evaluation of colposcopy accuracy through the results of a QC/QA assessment from a survey in Italian tertiary-level academic and teaching hospitals. A web-based, user-friendly platform based on 100 colposcopic digital images was forwarded to colposcopists with different levels of experience. Seventy-three participants were asked to identify colposcopic patterns, provide personal impressions, and indicate the correct clinical practice. The data were correlated with a panel of experts' evaluation and with the clinical/pathological data of the cases. Overall sensitivity and specificity with the threshold of CIN2+ accounted for 73.7% and 87.7%, respectively, with minor differences between senior and junior candidates. Identification and interpretation of colposcopic patterns showed full agreement with the experts' panel, ranging from 50% to 82%, in some instances with better results from junior colposcopists. Colposcopic impressions correlated with a 20% underestimation of CIN2+ lesions, with no differences linked to level of experience. Our results demonstrate the good diagnostic performance of colposcopy and the need for improving accuracy through QC assessments and adhesion to standard requirements and recommendations.
Strong evidence exists that the host’s immune system plays a crucial role for the development of human papillomavirus-related cervical premalignant and malignant lesions. In particular, effective ...cell-mediated immunity (CMI) promotes spontaneous infection clearance and cancer precursors regression in healthy subjects, while immunosuppressed individuals are more likely to experience infection persistence, cervical intraepithelial neoplasia (CIN) lesions, and cervical cancer. In this study, the prognostic significance of immunohistochemical profiling of CD4+ T-cells, CD8+ T-cells, dendritic cells (CD11c+), T-bet+, and GATA-3+ transcription factors has been studied in surgical specimens of 34 consecutive women affected by high-grade cervical intraepithelial neoplasia (CIN2-3) submitted to cervical conization. Results have been correlated with the clinical outcomes at 24 months after treatment and statistically analyzed. Higher rates of CD4+ T-cells, CD11c+ dendritic cells, and T-bet+ transcription factor positivity showed a strong statistically significative correlation with favourable clinical outcomes (P≤0.0001). These data reinforce the evidence of the relevance of the host’s immune status in the natural history of HPV-related cervical disease and add a prognostic significance of the cervical immunological profile in terms of predicting significant lower recurrence rates.
Primary cervical melanocytic schwannomas, arising from the sympathetic chain, are very rare pigmented neural sheath tumors that, both grossly and clinically, are often misdiagnosed with other more ...frequent lesions of the uterine cervix. Literature review accounts for seventeen published cases of schwannomas of the cervix, ten of which are malignant and seven benign. Pathological examination with immunostaining techniques is essential for the correct diagnosis of these tumors. We report a case of primary cervical schwannoma in a 32-year-old female who was referred to our department at 13 weeks of gestation with a diagnosis of malignant melanoma of the cervix. Pathological review detailed a neoplasm with a myxoid spindle cell component and a minority of small epithelioid cells, with a low-malignant potential proliferation index: morphological and immunocytochemical findings were compatible with the diagnosis of nerve sheath tumor, type schwannoma. The patient underwent a vaginal trachelectomy and a prophylactic Shirodkar’s cerclage. Pregnancy was carried on without any negative event. The patient delivered by a caesarean section a healthy female newborn. Placental histology was negative. After 6 years from the first diagnosis, the patient is healthy and disease free.
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