Remission of HPV-Related Diseases by Antivirals for Herpesvirus: Clinical Cases and a Literature Review.

Epidemiological studies have shown that HPV-related diseases are the most prevalent sexually transmitted infections. In this context, this report will present various clinical cases demonstrating the effectiveness of Acyclovir (ACV) or its prodrug Valaciclovir (VCV), both acyclic guanosine analogs commonly used for the treatment of HHV-1 and HHV-2, for the treatment of HPV-related diseases. The report shows the remission of five cases of penile condyloma and a case of remission in a woman affected by cervical and vaginal condylomas and a vulvar giant condyloma acuminate of Buschke and Lowenstein. The literature review shows that ACV is effective in treating skin warts when administered orally, topically, and intralesionally, suggesting its therapeutic potential in other diseases associated with HPV. ACV was also used successfully as an adjuvant therapy for juvenile and adult forms of laryngeal papillomatosis, also known as recurrent respiratory papillomatosis, prolonging the patient's symptom-free periods. Although the prevention of HPV infections is certainly achieved with the HPV vaccine, ACV and VCV have shown to be effective even against genotypes not included in the current vaccine and can be helpful for those problematic clinical cases involving unvaccinated individuals, immunocompromised patients, people who live with HIV, or non-responders to the vaccine. We and others concluded that randomized clinical trials are necessary to determine the efficacy of ACV and VCV for HPV-related diseases.

Conventional therapy for genital herpesvirus and remission of HPV-related lesions: a case series.

This report covers the case of 7 women affected by pathologies related to genital Herpesvirus and Papillomavirus. They were referred to the gynaecology outpatient clinic for colposcopic examination, and received pharmacological antiviral treatment. The patients presented clinical signs of genital Herpesvirus infections in the cervix and vulva. Cervical lesions and condylomatosis, which are characteristic of Papillomavirus infections were also detected, and patients underwent cervical cancer screening. Patients received oral and topical treatment with Acyclovir or oral treatment with Valacyclovir. During weekly or biweekly gynaecological follow-up visits, patients showed different times of remission of genital Herpesvirus. During the antiviral treatments, the vulvar and cervical Papillomavirus lesions also showed complete resolution with restitutio ad integrum of the tissues, and no recurrence at follow-up visits. Herpesvirus and Papillomavirus infections are often associated in genital infections and, as sexual transmitted infections, share the same risk factors. In the cases presented, the observed remission of HPV-related pathologies during Acyclovir and Valaciclovir treatments may suggest that antivirals are also effective in the treatment of HPV lesions. The cases described could pave the way for further investigations and clinical studies.

Mesothelioma families without inheritance of a BAP1 predisposing mutation.

Familial malignant mesothelioma clusters are ideal candidates to explore BAP1 genomic status as a predisposing risk factor. We report data on BAP1 analysis in four families with multiple mesothelioma cases to investigate possible BAP1 alterations associated with an inherited cancer syndrome. We also recorded family history of cancer and assessed asbestos exposure. By genomic direct sequencing, we found no evidence of a BAP1 germline mutation in tumor DNA samples (one mesothelioma per family: n = 3 epithelioid; n = 1 biphasic). On the other hand, we identified a novel BAP1 somatic alteration (c.329_335delinsTC) in exon 5 (n = 1 biphasic), and we hypothesized the occurrence of somatic inactivating events not identifiable by sequencing in the other cases (n = 3 epithelioid), as demonstrated by the loss of nuclear BAP1 immunostaining. History of other cancers was in sites not typical of the BAP1 cancer syndrome. Asbestos exposure was occupational (n = 2 clusters), household (n = 1), and unknown (n = 1). These family units without inheritance of a BAP1 predisposing mutation expand the number of unmutated germline BAP1 families with multiple mesothelioma cases. This suggests that besides the exposure to asbestos other currently unknown genetic or epigenetic factors may be responsible for the high incidence of mesothelioma in BAP1-unmutated families.

Pathology reporting of malignant pleural mesothelioma first diagnosis: A population-based approach.

Accurate pathologic diagnosis and reporting in malignant pleural mesothelioma are essential for clinical care, and cancer registration. Practical guidelines for pathologists are provided in publications and textbooks but it is unclear how these recommendations are applied in routine practice. We investigated the characteristics of pathology reports, and the extent to which they meet guideline standards. We reviewed 819 pathology reports relating to a first diagnosis of malignant pleural mesothelioma. Data sources were a regional section of the Italian network of the Mesothelioma Registry (2001-2014) and a pathology archive (1990-2000). We evaluated tumor characteristics, the diagnosis field including terminology and immunohistochemistry (IHC) workup, and report completeness (the proportion of items recorded). We investigated also two IHC panels identified by the most used markers in current practical guidelines, one best suited for epithelioid mesotheliomas (combinations of at least 2 positive and at least 2 negative mesothelioma markers) and the other best suited for sarcomatoid mesotheliomas (positive mesothelioma markers plus cytokeratins). Reports (753 histology, 66 cytology, IHC-confirmed 86%) were 74% complete and always narrative. Missing data were related to clinical history (76%), tumor laterality (61%), specimen size (38%), and histological subtype (23%). The proportion of cases with IHC was higher for epithelioid (90%) than sarcomatoid mesothelioma (87%). Compliance to IHC recommendations was higher for epithelioid (59%) than sarcomatoid mesothelioma (11%). The mean number of stains was significantly higher for sarcomatoid than epithelioid mesothelioma (p<0.000; Kruskal-Wallis test). Our findings show that although guidelines are designed to improve actual reporting practices, there is ample room for improvement in their application to standardize the diagnosis of mesothelioma. Synoptic pathology reporting needs to be implemented to better utilize pathology information.

Familial malignant mesothelioma: a population-based study in central Italy (1980-2012).

Malignant mesothelioma is a sporadic cancer linked to asbestos exposure. Its occurrence among blood relatives (familial mesothelioma) may point to genetic susceptibility or shared exposures. The burden of the familial disease is unknown. The aims of the study were to assess at population level the proportion of familial mesotheliomas among all mesotheliomas and to investigate the family history of cancer among relatives of mesothelioma cases. We actively searched familial clusters based on a mesothelioma registry from central Italy (5.5 million people, 10% of the Italian population) of the National Mesothelioma Register network (ReNaM) as well as a pathology-based archive. Among 997 incident mesotheliomas recorded in a 32-year-period (1980-2012), we detected 13 clusters and 34 familial cases, accounting for 3.4% of all mesotheliomas. The most common clusters where those with affected siblings and unaffected parents. Asbestos exposure was occupational (n=7 clusters), household (n=2), environmental (n=1), or not attributable for insufficient information (n=3). There were 25 additional cancers in nine families. Some were cancer sites for which there is sufficient evidence (lung and larynx) or limited evidence (stomach and colon) of causal association with asbestos. The results suggest potential genetic recessive effects in mesothelioma that interact with asbestos exposure, but it is not possible to estimate the specific proportion attributable to each of these components.

Comparison of conventional Papanicolaou smears and fluid-based, thin-layer cytology with colposcopic biopsy control in central Italy: a consecutive sampling study of 461 cases.

The aim of this study was to compare the cytologic diagnosis and specimen adequacy of conventional Papanicolaou (CP) and fluid-based, thin-layer [ThinPrep (TP), Cytyc, Boxborough, MA] cervical cytology in a population from central Italy. CP and TP samples were collected simultaneously using a consecutive sampling method on women presenting for cervical screening. Colposcopy was performed as clinically indicated, and biopsy results were compared with cytologic diagnoses. Among the 461 patients included in the study, 413 were negative at both CP and TP, 9 had unsatisfactory results at both tests and 39 patients presented abnormal results at CP, TP or both. Cohen's Kappa was 0.77 showing good agreement between CP and TP test results. Histological data were available for 20 (51.28%) of the 39 patients with at least one positive test. Among the 13 patients with HSIL at histology, 7 had HSIL at CP (sensitivity 53.85%) and 5 at TP (sensitivity 38.46%). For all three patients with squamous cell carcinoma (SCC) at histology, CP and TP had shown the same diagnosis (sensitivity 100%). The positive predictive values were 33.33% for CP and 25.0% for TP regarding the LSIL diagnosis and 100% for both CP and TP regarding HSIL and SCC diagnoses. Our results may be influenced by the consecutive sampling procedure.

[Estimates of pleural mesothelioma incidence in the Lazio region (Italy), 1997-2000]. / Stime di incidenza del mesotelioma pleurico nel Lazio, 1997-2000.

BACKGROUND: Malignant mesothelioma is indicative of past exposure to asbestos. In recent years an increase of incidence and mortality from malignant mesothelioma has been observed. Recent legislation in Italy requires nation-wide registration of asbestos-related pathologies. We conducted a preparatory study for systematic recording of cases of malignant pleural mesothelioma in the Lazio region. OBJECTIVES: To register new diagnoses of malignant mesothelioma, to estimate the incidence in the Lazio region, and to evaluate possible survey instruments. METHODS: We conducted a systematic study of hospital admissions in the region with diagnosis of cancer of the pleura (ICD-IX 163) in the period 1997-2000. Clinical information and results of diagnostic tests were requested for 530 patients from the hospitals involved. Using the capture-recapture method, it was possible to estimate the accuracy of the data we compiled using hospital admissions as the data source (76.8%, 95% C.I.=76.4-77.3). RESULTS: After careful review of clinical documentation, the diagnosis of malignant mesothelioma of the pleura was confirmed in 31.6% of cases (156 cases diagnosed). The percentage of confirmed cases has risen over the years (from 21% in 1997 to 45.1% in 2000) and it was higher in large public hospitals than in other types of health care facilities. On the basis of 156 confirmed cases of mesothelioma (116 males and 40 females), we estimated the annual incidence of the disease in the Lazio region as 1.73 new cases per 100,000 inhabitants among men and 0.47 new cases per 100,000 inhabitants among women. CONCLUSIONS: The results show that the incidence of mesothelioma in the region is consistent with national data, falling in the middle of the range for all Italian regions. However, some areas emerge (for example, Colleferro, Civitavecchia, Tarquinia, Ferentino, Gaeta, Aprilia, Pomezia) that have particularly high rates, probably in relation to past occupational asbestos exposure. The role of diffuse environmental exposure in Rome may warrant further investigation.

Malignant mesothelioma in Rome and Latium region, 1993-2001.

AIMS AND BACKGROUND: Epidemiological studies on malignant mesothelioma have provided evidence on the etiologic role of occupational asbestos exposure and, to some extent, domestic and residential exposures. Less attention has been given to the occurrence of mesothelioma in urban areas where large quantities of asbestos have been employed in the past. The purpose of the study was to investigate the occurrence of mesothelioma in patients living in the urban area of Rome and in other parts of the Latium Region and the patterns of asbestos exposure. METHODS AND STUDY DESIGN: A pathology-based, malignant mesothelioma archive operating in Rome, Italy, was the source of cases. Included in the survey were cases resident in Latium and diagnosed in the period January 1, 1993, through December 31, 2001. Information on asbestos exposure was derived from interviews to the patient or his/her next of kin and from available medical records. RESULTS: The case series included: 114 males and 53 females; total, 167. Information on asbestos exposure was available for 138 cases (83%). Occupational exposure was ascertained or suspected for 33% of cases resident in Rome and 63% of those resident in other municipalities of Latium. Sex ratio was 1.6 in Rome and 3.3 in Latium. CONCLUSIONS: The high prevalence of women among mesothelioma cases and lower proportion of occupational exposure in Rome versus the other municipalities of Latium suggest a possible role of environmental asbestos exposure in the urban area.