Penile Intraepithelial Neoplasia Research Articles

Incidence of external genital lesions related to human papillomavirus among Mexican men. A cohort study.

To determine external genital lesion (EGL) incidence -condyloma and penile intraepithelial neoplasia (PeIN)- and genital HPV-genotype progression to these EGLs. Participants (healthy males 18- 74y from Cuernavaca, Mexico, recruited 2005-2009, n=954) underwent a questionnaire, anogenital examination, and sample collection every six months;including excision biopsy on suspicious EGL with histological confirmation.Linear array assay PCR characterized 37 high/low-risk HPV-DNA types. EGL incidence and cumulative incidence were calculated, the latter with Kaplan-Meier. EGL incidence was 1.84 (95%CI=1.42-2.39) per 100-person-years (py); 2.9% (95%CI=1.9-4.2) 12-month cumulative EGL.Highest EGL inci- dence was found in men 18-30 years:1.99 (95%CI=1.22-3.25) per 100py. Seven subjects had PeIN I-III (four with HPV16). HPV11 most commonly progresses to condyloma (6-month cumulative incidence=44.4%, 95%CI=14.3-137.8). Subject with high-risk sexual behavior had higher EGL incidence. In Mexico, anogenital HPV infection in men is high and can cause condyloma. Estimation of EGL magnitude and associated healthcare costs is necessary to assess the need for male anti-HPV vaccination.

Penile intraepithelial neoplasia: Nomenclature, incidence and progression to malignancy in the Netherlands.

To determine the incidence of penile intraepithelial neoplasia in the Netherlands using a nationwide histopathology registry and to discuss the nomenclature of premalignant penile lesions. Data from patients in the Netherlands diagnosed with a premalignant penile lesion between January 1998 and December 2007 were collected from the nationwide histopathology registry (PALGA); this database covers all pathology reports of inhabitants in the Netherlands. The premalignant lesions included were erythroplasia of Queyrat; Bowen's disease; bowenoid papulosis; mild, moderate and severe dysplasia; and carcinoma in situ of the penis. The terminology used in the pathological reports was translated to penile intraepithelial neoplasia. The grading was made analogous to that of vulvar premalignant lesions. The PALGA database enrolled 380 patients with premalignant penile lesions. Severe premalignant lesions, penile intraepithelial neoplasia III, were found in 254 patients (67%), penile intraepithelial neoplasia II in 84 (22%) and penile intraepithelial neoplasia I in 42 patients (11%). Most lesions were located on the prepuce (45%), followed by glans (38%) and shaft (3%). The median age of patients with penile intraepithelial neoplasia was 58 years. Progression to malignant disease occurred (2% for penile intraepithelial neoplasia I vs 7% for penile intraepithelial neoplasia III) in 26 patients. Penile intraepithelial neoplasia is a rarely diagnosed condition. Because of the wide variation of terms used for premalignant intraepithelial neoplasia of the penis, we recommend restricting this nomenclature to penile intraepithelial neoplasia.

Molecular Detection of Equus caballus Papillomavirus Type 2 in Genital Swabs From Healthy Horses in the Republic of Korea

Equus caballus papillomavirus type 2 (EcPV-2) is implicated in genital neoplasms in horses, including equine penile papillomas, penile intraepithelial neoplasia, and squamous cell carcinoma (SCC). This virus seldom regresses spontaneously and can result in the development of SCC, which may result in significant clinical damage and economic cost. However, the prevalence of this virus is unknown in clinically unaffected horses. The aim of this study was to determine the prevalence of EcPV-2 DNA in genital swabs from healthy horses in the Republic of Korea and to investigate genetic variability within EcPV-2. A total of 797 genital swab samples obtained from Thoroughbred horses (35 stallions and 762 mares) were tested for the presence of the EcPV-2 gene E1 using a polymerase chain reaction (PCR) assay. Positive results were confirmed by repeat PCR to detect the presence of E6 and amplicon sequencing. Equus caballus papillomavirus type 2 DNA was detected in 1% (8/762) of mare swabs but in none of stallion swabs (0/35). All EcPV-2–positive mares had been imported from the United States. Equus caballus papillomavirus type 2 E6 gene sequences were used for phylogenetic analysis and revealed three subdivisions related to the European strains, and three isolates were located on two separate branches. This study documents the molecular prevalence and phylogenetic analysis of EcPV-2 DNA in the Republic of Korea.

80 - Occurrence of penile intraepithelial neoplasia in histological samples from circumcisions

80 - Occurrence of penile intraepithelial neoplasia in histological samples from circumcisions

Efficacy, effectiveness and safety of vaccination against human papillomavirus in males: a systematic review

BackgroundHuman papillomavirus (HPV) vaccination is safe and effective in preventing cervical cancer in females. As HPV infections can also induce cancers of the anus, penis and oral cavity, male vaccination is also advocated, but systematic reviews on efficacy and safety in males are lacking.MethodsWe performed a systematic review on the efficacy, effectiveness and safety of HPV vaccination in males of any age. MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were searched from inception to April 2017.ResultsWe identified 5196 articles and seven studies (four randomized controlled trials (RCTs), three non-randomized studies) were included, comprising a total of 5294 participants. Vaccine efficacy against at least 6-month persisting anogenital HPV 16 infections was 46.9% (95% confidence interval (CI) 28.6–60.8%), whereas efficacy against persisting oral infections was 88% (2–98%). A vaccine efficacy of 61.9% (21.4–82.8%) and 46.8% (− 20 to –77.9%) was observed against anal intraepithelial neoplasia grade 2 and grade 3 lesions, respectively. No meaningful estimates were available on vaccine efficacy or effectiveness against penile intraepithelial neoplasia grade 2 or 3, and no data were identified for anal, penile or head and neck squamous cell cancer. In participants who were HPV-seronegative and PCR-negative at enrolment, efficacy against all outcomes was higher as compared to seropositive and/or PCR-positive individuals. Risk of bias was low in three RCTs and high in one, while the three non-randomized studies were at serious to critical risk of bias. Grading of Recommendations Assessment, Development and Evaluation evidence quality was moderate to low for most outcomes.ConclusionsHPV vaccination in males is moderately effective against persistent anogenital HPV infection and high-grade anal intraepithelial lesions in studies where the population consists mainly of HPV-infected males. Vaccine effectiveness was high in study groups comprising HPV-naïve males. This supports a recommendation for vaccination of boys before the onset of sexual activity with the goal of establishing optimal vaccine-induced protection. Mathematical modelling studies will still be needed to assess the effects of adding males to existing HPV vaccination programs in females.Trial registrationProspective Register for Systematic Reviews (PROSPERO) registration CRD42016038965.

Les néoplasies intra-épithéliales du pénis

Penile intra-epithelial neoplasia (PIN) are precancerous lesions, characterized by architectural and cytological abnormalities of the genital epithelium, from which can arise squamous carcinomas. A literature review was performed on the Medline database, considering the articles listed between October 2007and October 2017dealing with PIN, using the following keywords "intraepithelial neoplasia" or "Bowen's disease" or "erythroplasia of Queyrat" or "bowenoid papulosis" and "penis». Papers were selected according to their language (English and French) and their relevance. One hundred seventy four articles related to PIN were listed. Twenty-five of them were selected for their relevance. The analysis of the references of these articles identified 6relevant papers published before October 2007, which were considered for this review based on a total of thirty-one articles. We describe clinical and pathological characteristics of PIN, emphasizing treatment modalities. Urologists should distinguish HPV-related and non HPV-related PIN, both of them sharing clinical presentation, but needing different management.

Ovarian and Uterine Dynamics in Criollo Breed Mares

Equus caballus papillomavirus type 2 (EcPV-2) is implicated in genital neoplasms in horses, including equine penile papillomas, penile intraepithelial neoplasia, and squamous cell carcinoma (SCC). This virus seldom regresses spontaneously and can result in the development of SCC, which may result in significant clinical damage and economic cost. However, the prevalence of this virus is unknown in clinically unaffected horses. The aim of this study was to determine the prevalence of EcPV-2 DNA in genital swabs from healthy horses in the Republic of Korea and to investigate genetic variability within EcPV-2. A total of 797 genital swab samples obtained from Thoroughbred horses (35 stallions and 762 mares) were tested for the presence of the EcPV-2 gene E1 using a polymerase chain reaction (PCR) assay. Positive results were confirmed by repeat PCR to detect the presence of E6 and amplicon sequencing. Equus caballus papillomavirus type 2 DNA was detected in 1% (8/762) of mare swabs but in none of stallion swabs (0/35). All EcPV-2–positive mares had been imported from the United States. Equus caballus papillomavirus type 2 E6 gene sequences were used for phylogenetic analysis and revealed three subdivisions related to the European strains, and three isolates were located on two separate branches. This study documents the molecular prevalence and phylogenetic analysis of EcPV-2 DNA in the Republic of Korea.

Combination of hCG and Deslorelin Acetate on the Induction of Ovulation in Mares: Changes in Follicular Fluid Protein Profile

Equus caballus papillomavirus type 2 (EcPV-2) is implicated in genital neoplasms in horses, including equine penile papillomas, penile intraepithelial neoplasia, and squamous cell carcinoma (SCC). This virus seldom regresses spontaneously and can result in the development of SCC, which may result in significant clinical damage and economic cost. However, the prevalence of this virus is unknown in clinically unaffected horses. The aim of this study was to determine the prevalence of EcPV-2 DNA in genital swabs from healthy horses in the Republic of Korea and to investigate genetic variability within EcPV-2. A total of 797 genital swab samples obtained from Thoroughbred horses (35 stallions and 762 mares) were tested for the presence of the EcPV-2 gene E1 using a polymerase chain reaction (PCR) assay. Positive results were confirmed by repeat PCR to detect the presence of E6 and amplicon sequencing. Equus caballus papillomavirus type 2 DNA was detected in 1% (8/762) of mare swabs but in none of stallion swabs (0/35). All EcPV-2–positive mares had been imported from the United States. Equus caballus papillomavirus type 2 E6 gene sequences were used for phylogenetic analysis and revealed three subdivisions related to the European strains, and three isolates were located on two separate branches. This study documents the molecular prevalence and phylogenetic analysis of EcPV-2 DNA in the Republic of Korea.

Approach to the Study of the Relationship Between DNA Damage and Oxidative Stress in Equine Semen

Equus caballus papillomavirus type 2 (EcPV-2) is implicated in genital neoplasms in horses, including equine penile papillomas, penile intraepithelial neoplasia, and squamous cell carcinoma (SCC). This virus seldom regresses spontaneously and can result in the development of SCC, which may result in significant clinical damage and economic cost. However, the prevalence of this virus is unknown in clinically unaffected horses. The aim of this study was to determine the prevalence of EcPV-2 DNA in genital swabs from healthy horses in the Republic of Korea and to investigate genetic variability within EcPV-2. A total of 797 genital swab samples obtained from Thoroughbred horses (35 stallions and 762 mares) were tested for the presence of the EcPV-2 gene E1 using a polymerase chain reaction (PCR) assay. Positive results were confirmed by repeat PCR to detect the presence of E6 and amplicon sequencing. Equus caballus papillomavirus type 2 DNA was detected in 1% (8/762) of mare swabs but in none of stallion swabs (0/35). All EcPV-2–positive mares had been imported from the United States. Equus caballus papillomavirus type 2 E6 gene sequences were used for phylogenetic analysis and revealed three subdivisions related to the European strains, and three isolates were located on two separate branches. This study documents the molecular prevalence and phylogenetic analysis of EcPV-2 DNA in the Republic of Korea.

Effect of Sperm Concentration of the Frozen Ejaculate of Donkeys on Post-thaw Semen Quality

Equus caballus papillomavirus type 2 (EcPV-2) is implicated in genital neoplasms in horses, including equine penile papillomas, penile intraepithelial neoplasia, and squamous cell carcinoma (SCC). This virus seldom regresses spontaneously and can result in the development of SCC, which may result in significant clinical damage and economic cost. However, the prevalence of this virus is unknown in clinically unaffected horses. The aim of this study was to determine the prevalence of EcPV-2 DNA in genital swabs from healthy horses in the Republic of Korea and to investigate genetic variability within EcPV-2. A total of 797 genital swab samples obtained from Thoroughbred horses (35 stallions and 762 mares) were tested for the presence of the EcPV-2 gene E1 using a polymerase chain reaction (PCR) assay. Positive results were confirmed by repeat PCR to detect the presence of E6 and amplicon sequencing. Equus caballus papillomavirus type 2 DNA was detected in 1% (8/762) of mare swabs but in none of stallion swabs (0/35). All EcPV-2–positive mares had been imported from the United States. Equus caballus papillomavirus type 2 E6 gene sequences were used for phylogenetic analysis and revealed three subdivisions related to the European strains, and three isolates were located on two separate branches. This study documents the molecular prevalence and phylogenetic analysis of EcPV-2 DNA in the Republic of Korea.

Cooled Storage Induces Capacitation-like Changes in Equine Spermatozoa

Equus caballus papillomavirus type 2 (EcPV-2) is implicated in genital neoplasms in horses, including equine penile papillomas, penile intraepithelial neoplasia, and squamous cell carcinoma (SCC). This virus seldom regresses spontaneously and can result in the development of SCC, which may result in significant clinical damage and economic cost. However, the prevalence of this virus is unknown in clinically unaffected horses. The aim of this study was to determine the prevalence of EcPV-2 DNA in genital swabs from healthy horses in the Republic of Korea and to investigate genetic variability within EcPV-2. A total of 797 genital swab samples obtained from Thoroughbred horses (35 stallions and 762 mares) were tested for the presence of the EcPV-2 gene E1 using a polymerase chain reaction (PCR) assay. Positive results were confirmed by repeat PCR to detect the presence of E6 and amplicon sequencing. Equus caballus papillomavirus type 2 DNA was detected in 1% (8/762) of mare swabs but in none of stallion swabs (0/35). All EcPV-2–positive mares had been imported from the United States. Equus caballus papillomavirus type 2 E6 gene sequences were used for phylogenetic analysis and revealed three subdivisions related to the European strains, and three isolates were located on two separate branches. This study documents the molecular prevalence and phylogenetic analysis of EcPV-2 DNA in the Republic of Korea.

Validation of a Fixable Stain for Assessing the Viability of Stallion Sperm

Equus caballus papillomavirus type 2 (EcPV-2) is implicated in genital neoplasms in horses, including equine penile papillomas, penile intraepithelial neoplasia, and squamous cell carcinoma (SCC). This virus seldom regresses spontaneously and can result in the development of SCC, which may result in significant clinical damage and economic cost. However, the prevalence of this virus is unknown in clinically unaffected horses. The aim of this study was to determine the prevalence of EcPV-2 DNA in genital swabs from healthy horses in the Republic of Korea and to investigate genetic variability within EcPV-2. A total of 797 genital swab samples obtained from Thoroughbred horses (35 stallions and 762 mares) were tested for the presence of the EcPV-2 gene E1 using a polymerase chain reaction (PCR) assay. Positive results were confirmed by repeat PCR to detect the presence of E6 and amplicon sequencing. Equus caballus papillomavirus type 2 DNA was detected in 1% (8/762) of mare swabs but in none of stallion swabs (0/35). All EcPV-2–positive mares had been imported from the United States. Equus caballus papillomavirus type 2 E6 gene sequences were used for phylogenetic analysis and revealed three subdivisions related to the European strains, and three isolates were located on two separate branches. This study documents the molecular prevalence and phylogenetic analysis of EcPV-2 DNA in the Republic of Korea.

PIK3CA copy number aberration and activation of the PI3K-AKT-mTOR pathway in varied disease states of penile cancer.

BackgroundTherapeutic targeting of the PI3K-AKT-mTOR pathway may benefit patients with advanced penile squamous cell carcinoma (PSCC).ObjectivesTo determine the prevalence of PIK3CA copy number gain and correlate this with the activity status of PI3K-AKT-mTOR pathway in pre-malignant penile intraepithelial neoplasia (PeIN) and invasive PSCC.Materials and methodsArchival tissue blocks were obtained from 58 PeIN and 244 primary PSCC patients treated at St George’s Hospital. PIK3CA copy number status (CNS) was assessed by fluorescence in-situ hybridisation. High-risk HPV DNA was detected with INNO-LiPA assay. p16INK4A, p-AKT and p-mTOR protein expression were assessed using immunohistochemistry (IHC).ResultsIncreased prevalence of PIK3CA copy number gain was seen in PSCC in comparison to PeIN (84/199 (42%) vs. 10/58 (17%); p = 0.0009). Analysis of the p-AKT and p-mTOR revealed a tendency to a more common expression of cytoplasmic p-AKT (p = 0.1318), nuclear p-AKT (p<0.0001) and cytoplasmic mTOR (p = 0.0006) in PeIN than PSCC. A significant association between p-AKT cytoplasmic immunoexpression and PIK3CA CNS (p = 0.0404) was found in PeIN.ConclusionOverall, PIK3CA copy number gain correlated with activation of the PI3K-AKT-mTOR pathway in PeIN and activation of this pathway is primarily involved in early penile carcinogenesis. Based on these results therapeutic targeting of this pathway in advanced PSCC is unlikely to produce significant clinical benefit. Future studies will need to focus on alternative therapeutic targets.

A study into the association between local recurrence rates and surgical resection margins in organ-sparing surgery for penile squamous cell cancer.

To evaluate the significance of close surgical margins in organ-sparing surgery (OSS) in the treatment of penile squamous cell carcinoma (pSCC) and clinicopathological factors that may influence local recurrence. At our tertiary referral centre, between March 2001 and September 2012, 332 patients treated with OSS for pSCC had clear surgical margins. As the focus was the impact of close clear margins on local recurrence, patients with positive margins were excluded for the purpose of this study. Our overall positive margin rate for OSS in penile cancer is 7.6% (42 patients). Analysis was carried out on an on-going prospective database, including prospective accurate pathological recording of surgical margins. Patients underwent OSS after multidisciplinary team (MDT) discussion. Local recurrence was the primary outcome measured and Fisher's exact test and time-to-recurrence curves were used in the analysis. All local recurrences were scrutinised by the MDT and were categorised into: true recurrences or metachronous new occurrences (i.e. tumours arising from a background of penile intraepithelial neoplasia and forming on an epithelial surface not related to the site of initial resection). A multivariate analysis was also conducted to elucidate other factors influencing local recurrence. In all, 64% of the patients had a <5 mm clear deep surgical margin, with 16% clear by <1 mm. Overall, 4% of patients had a true local recurrence, with a median time to recurrence of 6 months. In all, 53% were due to embolic spread, with residual occult local disease accounting for 47%. There was a statistically significant relationship between cavernosal involvement (P = 0.014) and lymphovascular invasion (LVI; P = 0.001) and local recurrence. Although multivariate analysis revealed that the extent of clear margin was not a predictor of disease (P = 0.405), we found an increased risk of local recurrence in the clear margin cohort of <1 mm compared to those of >1 mm (P < 0.001). Those patients considered to have metachronous tumours were scrutinised by our MDT, and eight patients (2.4%) were found to have new occurrences. Our overall proportion of patients therefore needing further treatment for either new occurrences or recurrent disease after OSS stands at 6.4%. Overall the presence of local recurrent disease in OSS in our experience is low (4%). We report an embolic mechanism of local recurrence, strongly suggested by the presence of cavernosal involvement and LVI. We conclude that a deep clear margin of >1 mm has a very low risk of local recurrence in penile OSS.

Topical Therapy for non-invasive penile cancer (Tis)-updated results and toxicity.

Penile cancer is a rare malignancy estimated to affect 26,000 men globally each year. The association with penile cancer, in particular non-invasive disease, and human papilloma virus (HPV) is well known. Ninety-five percent of cases of penile cancer are squamous cell carcinoma (SCC), which are staged using the TNM staging system. Terminology describing the histological appearance of non-invasive penile cancer has changed with all cases grouped under the umbrella term of penile intraepithelial neoplasia (PeIN); either undifferentiated or differentiated. This replaces previous terms such as carcinoma in situ (CIS) and eponymous names such as Bowen’s disease. This change is recognised by the World Health Organisation (WHO). The topical treatments most commonly used for PeIN are 5-fluorouracil (5-FU) and imiquimod (IQ). Other treatments such as photodynamic therapy (PDT) are used but to a lesser degree. The evidence for all of these treatments is heterogenous with no randomised data available. Overall up to 57% complete response has been reported with a low number of serious adverse events. In this article, we aim to review the available evidence for the topical treatment of non-invasive penile cancer specifically regarding its efficacy and toxicity.

The diagnosis and management of male genital lichen sclerosus: a retrospective review of 301 patients.

Male genital lichen sclerosus (MGLSc) is an acquired, chronic, inflammatory skin disease that is associated with significant morbidity and squamous cell carcinoma of the penis (PSCC). However, some clinical, diagnostic and management controversies endure, including the relationship with penile intraepithelial neoplasia (PeIN). To clarify clinical presentations, diagnostic approaches, histological findings, response to treatment and the relationship with PeIN. Retrospective review of patients with a diagnosis of MGLSc who attended a specialist male genital dermatoses clinic. 301 patients were identified: 260 had isolated MGLSc and 41 both MGLSc and PeIN. Referrals were made from the local Urology and Andrology departments (128), primary care (89), GUM (54), other dermatology departments (28) and other specialties (2). In isolated MGLSc, 94.6% were diagnosed clinically with 93.5% accuracy (based on data from subsequent circumcisions). In combined MGLSc/PeIN, 85.4% were diagnosed following diagnostic biopsy and 14.6% retrospectively after circumcision. In isolated MGLSc, 50% were treated topically, and 50% required surgery. In MGLSc/PeIN, 78% required surgical interventions. In isolated MGLSc, 92.2% achieved resolution of symptoms, 3.5% were awaiting procedures, and 4.8% were receiving ongoing topical therapy. In MGLSc/PeIN, 90.2% achieved clearance, 2.4% were waiting surgery, and 7.3% were treated topically. Only 2.7% reported ongoing symptoms, all in patients treated surgically. None progressed to PSCC. MGLSc is generally a disease of the uncircumcised; the majority of cases of MGLSc are accurately diagnosed clinically; suspected PeIN or PSCC requires histological confirmation; circumcision histology can be non-specific; most men are either cured by topical treatment with ultrapotent corticosteroid (53.1%) or by circumcision (46.9%); surgical intervention is required in most cases of concomitant MGLSc and PeIN; the majority of patients with MGLSc alone or with MGLSc and PeIN remit with this approach; effective management appears to negate the risk of malignant transformation to PSCC.

Human Papillomavirus (HPV) Genotypes in Condylomas, Intraepithelial Neoplasia, and Invasive Carcinoma of the Penis Using Laser Capture Microdissection (LCM)-PCR: A Study of 191 Lesions in 43 Patients.

Laser capture microdissection-polymerase chain reaction (LCM-PCR) supported by p16 was used for the first time to demonstrate human papillomavirus (HPV) DNA in histologically specific penile lesions, which were as follows: squamous hyperplasia (12 lesions, 10 patients), flat lesions (12 lesions, 5 patients), condylomas (26 lesions, 7 patients), penile intraepithelial neoplasia (PeIN) (115 lesions, 43 patients), and invasive squamous cell carcinomas (26 lesions, 26 patients). HPV was detected by whole-tissue section and LCM-PCR. LCM proved to be more precise than whole-tissue section in assigning individual genotypes to specific lesions. HPV was negative or very infrequent in squamous hyperplasia, differentiated PeIN, and low-grade keratinizing variants of carcinomas. HPV was strongly associated with condylomas, warty/basaloid PeIN, adjacent flat lesions, and warty/basaloid carcinomas. A single HPV genotype was found in each lesion. Some condylomas and flat lesions, especially those with atypia, were preferentially associated with high-risk HPV. Unlike invasive carcinoma, in which few genotypes of HPV were involved, there were 18 HPV genotypes in PeIN, usually HPV 16 in basaloid PeIN but marked HPV heterogeneity in warty PeIN (11 different genotypes). Variable and multiple HPV genotypes were found in multicentric PeIN, whereas unicentric PeIN was usually related to a single genotype. There was a correspondence among HPV genotypes in invasive and associated PeIN. p16 was positive in the majority of HPV-positive lesions except condylomas containing LR-HPV. p16 was usually negative in squamous hyperplasia, differentiated PeIN, and low-grade keratinizing variants of squamous cell carcinomas. In summary, we demonstrated that LCM-PCR was a superior research technique for investigating HPV genotypes in intraepithelial lesions. A significant finding was the heterogeneity of HPV genotypes in PeIN and the differential association of HPV genotypes with subtypes of PeIN. The presence of atypia and high-risk HPV in condylomas and adjacent flat lesions suggests a precursor role, and the correspondence of HPV genotypes in invasive carcinomas and associated PeIN indicates a causal relation. Data presented support the bimodal hypothesis of penile cancer carcinogenesis in HPV-driven and non-HPV-driven carcinomas and justify the current WHO pathologic classification of PeIN in special subtypes.

HPV-related external genital lesions among men residing in Brazil

The aims of this study were to determine the incidence of external genital lesions (EGLs), specifically histologically confirmed condyloma (genital warts) and Penile Intraepithelial Neoplasia (PeIN), and genital HPV infection progression to EGLs among healthy men aged 18–73 residing in Brazil. Subjects included 1118 men enrolled in the HPV Infection in Men (HIM) study between July 2005 and June 2009. At each visit, EGLs were biopsied and subjected to pathological evaluation. HPV status in genital swabs and biopsies was determined by Linear Array and INNO-LiPA, respectively. Age-specific EGLs incidence and the proportion and median time to EGL development were estimated. Kaplan–Meier cumulative incidence rates at 6, 12, and 24 months were determined. During follow-up, 73 men developed an incident EGL. Men could develop multiple EGLs and there were 36 men with condyloma, 27 men with lesions suggestive of condyloma, six men with PeIN, and 20 men with non-HPV lesions. HPV-positive men who developed EGLs were younger (p=0.002) than men that did not develop lesions. Among the 815 men with HPV infection, 4% progressed to EGL with the same HPV detected in the swab. During follow up, 15.7% of genital HPV-6 and HPV-11 infections progressed to condyloma (median progression time of nine months for HPV-6 versus 6.8 months for HPV-11). Approximately 1% of HPV-16 infections progressed to PeIN with a median progression time of 25 months. HPV types covered by the 4-valent HPV vaccine were detected in 82.3% and 83.3% of condyloma and PeIN, respectively. The high burden of HPV and high frequency of progression to disease underscores the need to offer HPV prophylactic vaccination to men to reduce the overall burden of infection and diseases caused by HPV.

717 - Does residual penile intraepithelial neoplasia (PeIN) require adjuvant chemotherapy after surgical excision?

717 - Does residual penile intraepithelial neoplasia (PeIN) require adjuvant chemotherapy after surgical excision?

The variable morphological spectrum of penile basaloid carcinomas: differential diagnosis, prognostic factors and outcome report in 27 cases classified as classic and mixed variants

BackgroundBasaloid carcinomas of the penis, HPV-related tumors, are morphologically less homogenous than originally thought. The study objective was to evaluate the prognostic influence of the basaloid pattern in mixed tumors.MethodsWe studied 154 Mexican patients from the Hospital de Oncología, CMN, Mexico City (2000–2013) and found 27 with basaloid features in at least 20% of the sections classified as classic basaloid (8 cases), warty-basaloid (7), papillary-basaloid (5) and usual-basaloid squamous cell carcinomas (7). We evaluated patients’ age, site and size of tumor, histological classification, grade, thickness, anatomical level, vascular and perineural invasion, prognostic index score and node involvement. Penile intraepithelial neoplasia in adjacent epithelia was documented. Follow up ranged from 12–78 months. Statistical methods were Fisher’s exact test and Kruskal-Wallis test. Kaplan-Meier method and log-rank test were used for survival analysis. The cutoff for statistical significance was p <0.05.ResultsThere were not clinical differences. Microscopically types were distinctive and easy to separate. Usual-basaloid squamous cell carcinomas were smaller, thinner and rarely invaded corpora cavernosa, with a low prognostic index score. Classic basaloid, warty-basaloid and papillary-basaloid carcinomas had higher rates of vascular and perineural invasion and higher prognostic index scores. These findings correlated with the rate of nodal metastasis. The majority of patients with classic and papillary-basaloid neoplasms died from systemic metastasis (87.5 and 80%) whereas only 1 patient with usual-basaloid carcinoma died of the disease (14%).ConclusionsBasaloid carcinomas are not a single entity but a spectrum of variable histological architectures mixed with those of classic basaloid tumors. Identification of mature squamous cells in a basaloid carcinoma may be important to recognize and report because patients with these tumors may carry a better prognosis.