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Journal of Endocrinological... Feb 2024Human papillomavirus (HPV) infection is the most common sexually transmitted disease, in males and females worldwide. While the role of HPV in female diseases is well... (Review)
Review
PURPOSE
Human papillomavirus (HPV) infection is the most common sexually transmitted disease, in males and females worldwide. While the role of HPV in female diseases is well known and largely studied, males have negligibly been included in these programs, also because the proportion of women suffering and dying from HPV-related diseases is much larger than men. The aim of this review is to focus on HPV-related diseases in male patients.
METHODS
We performed a literature analysis on the electronic database PubMed. We considered randomized trials, observational and retrospective studies, original articles having as topic the relationship between HPV male infection and the following items: oral, anal penile cancers, warts, condylomas, male infertility, altered sperm parameters, anti-sperm antibodies (ASA). We also included experimental in vitro studies focused on the effects of HPV infection on oocyte fertilization, blastocyst development, and trophoblastic cell invasiveness. In addition, studies describing the adjuvant administration of the HPV vaccination as a possible strategy to promote HPV clearance from semen in infected males were included.
RESULTS
Regarding head and neck HPV-related diseases, the most important non-neoplastic disease is recurrent respiratory papillomatosis (RRP). Regarding neoplastic diseases, the proportion of head and neck cancers attributable to HPV has increased dramatically worldwide. In addition, nowadays, it is thought that half of head and neck squamous cell carcinomas (HNSCCs) cases in the United States are caused by infection with high-risk HPV. HPV is noteworthy in andrological practice too. It was described as having a high HPV prevalence, ranging between 50 and 70%, in male penile shaft, glans penis/coronal sulcus, semen as well as in scrotal, perianal, and anal regions. Moreover, in male patients, HPV infection has been associated, among other diseases, with penile cancers. HPV semen infection has been reported in about 10% in men from the general population and about 16% in men with unexplained infertility, although these data seem widely underestimated according to clinical experience. In particular, HPV semen infection seems to be most related to asthenozoospermia and to anti-sperm antibodies (ASAs).
CONCLUSIONS
HPV infection represents a health problem with a detrimental social and public impact. Despite this evidence, little has been done to date to widely promote vaccination among young males.
Topics: Humans; Male; Female; Papillomavirus Infections; Penile Neoplasms; Semen; Retrospective Studies; Spermatozoa; Antibodies
PubMed: 37770654
DOI: 10.1007/s40618-023-02192-3 -
Journal of Lower Genital Tract Disease Oct 2023Lichen sclerosus (LS) is a chronic inflammatory skin disease. In male patients, it usually involves the glans penis and foreskin and can cause phimosis or meatal...
OBJECTIVE
Lichen sclerosus (LS) is a chronic inflammatory skin disease. In male patients, it usually involves the glans penis and foreskin and can cause phimosis or meatal stenosis. The aim of this cross-sectional case-control study was to identify clinically important comorbidities in male patients with LS.
MATERIALS AND METHODS
By searching Turku University Hospital electronic health records, the authors identified 630 male patients diagnosed with LS between 2004 and 2020. To investigate possible comorbidities, the authors compared this patient group to a 10-fold larger control group.
RESULTS
The incidence of LS increased during the study period, from 5 to 27.5 per 100,000 men. Patients were most often diagnosed at 21 to 25 years of age. Patients with LS exhibited markedly increased risks of penile carcinoma (odds ratio [OR], 81.0; 95% CI = 10.82-3516.7; p < .001) and carcinoma in situ of the penis (OR = 60.5; 95% CI = 7.32-2738.9; p < .001). Patients also more commonly exhibited lichen planus (OR = 16.8; 95% CI = 8.97-32.39; p < .001), psoriasis (OR = 3.3; 95% CI = 1.80-5.70; p = .004), angina pectoris (OR = 1.8; 95% CI = 1.10-2.81; p = .013), obesity (OR = 2.6; 95% CI = 1.72-3.77; p < .001), type 2 diabetes (OR = 2.3; 95% CI = 1.74-3.09; p < .001), and hypertension (OR = 1.9; 95% CI = 1.53-2.37; p < .001). The most commonly performed urological procedures were operation for phimosis, uroflowmetry, and ultrasound measurement of residual urine.
CONCLUSIONS
Genital malignancies, other dermatological conditions, and diseases related to metabolic syndrome should be considered when treating patients with LS.
Topics: Humans; Male; Case-Control Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Lichen Sclerosus et Atrophicus; Phimosis; Young Adult; Adult
PubMed: 37729047
DOI: 10.1097/LGT.0000000000000769 -
Indian Journal of Cancer 2023Carcinoma penis is more common in India compared to the West. The role of chemotherapy in carcinoma penis is ambiguous. We analyzed the profile and outcomes of patients...
BACKGROUND
Carcinoma penis is more common in India compared to the West. The role of chemotherapy in carcinoma penis is ambiguous. We analyzed the profile and outcomes of patients with carcinoma penis treated with chemotherapy.
METHODS
We analyzed the details of all patients with carcinoma penis treated at our institute between 2012 and 2015. We collected particulars regarding demography, clinical presentation, treatment details, toxicities, and outcomes of these patients. Event-free and overall (OS) survival were calculated from the time of diagnosis until documentation of disease relapse/progression or death for the patients with advanced carcinoma penis who were eligible for chemotherapy.
RESULTS
There were 171 patients with carcinoma penis treated at our institute during the study period including 54 (31.6%) patients with stage I, 49 (28.7%) patients with stage II, 24 (14.0%) patients with stage III, 25 (14.6%) patients with stage IV, and 19 (11.1%) patients with recurrent disease at presentation. The present study included 68 patients with advanced carcinoma penis (stages III and IV) who were eligible for chemotherapy, with a median age of 55 years (range: 27-79 years). Sixteen patients received paclitaxel and carboplatin (PC) and 26 patients cisplatin and 5-FluoroUracil (CF). Neoadjuvant chemotherapy (NACT) was given to four patients with stage III and nine patients with stage IV disease. Of the 13 patients given NACT, we observed a partial response in five (38.5%), stable disease in two (15.4%), and progressive disease in five (38.5%) evaluable patients. Six (46%) patients underwent surgery after NACT. Only 28/54 (52%) patients received adjuvant chemotherapy. After a median follow-up of 17.2 months, the 2-year OS rates were 95.8, 89, 62.7, 51.9, and 28.6% for stages I, II, III, IV, and recurrent disease, respectively. The 2-year OS of patients who were given chemotherapy versus those who were not given chemotherapy were 52.7 and 63.2%, respectively (P = 0.762).
CONCLUSIONS
We report the real-world outcomes of two chemotherapeutic regimens used in consecutive patients with advanced carcinoma penis. Both PC and CF seemed effective and safe. However, approximately half of patients with advanced carcinoma penis do not receive the planned/indicated chemotherapy. We need further prospective trials regarding the sequencing, protocols and indications of chemotherapy in this malignancy.
Topics: Male; Humans; Adult; Middle Aged; Aged; Neoplasm Staging; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Carboplatin; Carcinoma; Chemotherapy, Adjuvant; Paclitaxel; Neoadjuvant Therapy; Penis
PubMed: 36861700
DOI: 10.4103/ijc.IJC_266_20 -
The American Journal of Surgical... Dec 2023Compared with vulva, precursor lesions of human papillomavirus (HPV)-independent invasive squamous cell carcinoma (SCC) of the penis are insufficiently characterized. We...
Compared with vulva, precursor lesions of human papillomavirus (HPV)-independent invasive squamous cell carcinoma (SCC) of the penis are insufficiently characterized. We analyzed the histologic and immunohistochemical characteristics of 70 peritumoral precursor lesions and correlated them with the histology and mutational profile of the adjacent HPV-negative invasive penile SCC. Atypical basal keratinocyte proliferation with variously elongated epithelial rete with premature squamatiziation, but regular superficial cornification, termed differentiated penile intraepithelial neoplasia (d-PeIN), were identified adjacent to 42/70 (60%) SCC (36/42 keratinizing ( P <0.001); 3 papillary, and 1 each verrucous, clear cell, sarcomatoid SCC). d-PeIN were associated with chronic inflammatory dermatoses (32/42; P <0.001), p53 overexpression (26/42; P <0.001), and hotspot mutations in TP53 (32/42; P <0.001), CDKN2A (26/42; P <0.001) or both (21/42; P =0.003) in the adjacent SCC. Cytoplasmic p16 ink4a overexpression in 5/42 d-PeIN correlated with CDKN2A missense mutations in the adjacent SCC. In all, 21/70 (30%) cornified verrucous or glycogenated verruciform precursors with minimal atypia and wild-type p53 (18/21; P <0.001) occurred adjacent to verrucous or papillary SCC (17/21; P <0.001) and keratinizing (4/21) SCC, which harbored mutations in HRAS and/or PIK3CA (12/21; P <0.004). Undifferentiated p16 ink4a -negative full-thickness precursors were identified in 7/70 (10%) SCC. Four histologically different HPV-independent penile precursor lesions can be assigned to 2 major genetic/biological pathways with characteristic highly differentiated precursors requiring different clinical management decisions. These include d-PeIN in chronic inflammatory dermatoses, with p53 overexpression and TP53/CDKN2A mutations, and the p53 wild-type verrucous and verruciform precursors unassociated with dermatoses, but with mutations in oncogenes PIK3CA and HRAS .
Topics: Male; Female; Humans; Papillomavirus Infections; Tumor Suppressor Protein p53; Human Papillomavirus Viruses; Skin Neoplasms; Carcinoma in Situ; Carcinoma, Squamous Cell; Penile Neoplasms; Penis; Papillomaviridae; Class I Phosphatidylinositol 3-Kinases; Vulvar Neoplasms
PubMed: 37768009
DOI: 10.1097/PAS.0000000000002130 -
Human Genomics Dec 2023The effect of SPP1 in squamous cell carcinoma of the penis (PSCC) remained unknown. We attempted to clarify the function of the SPP1 gene in PSCC.
BACKGROUND
The effect of SPP1 in squamous cell carcinoma of the penis (PSCC) remained unknown. We attempted to clarify the function of the SPP1 gene in PSCC.
METHOD
Eight paired penile cancer specimens (including penile cancer tissue, paracancerous tissue, and positive lymph node tissue) subjected to whole transcriptome sequencing were analysed to identify differentially expressed genes. We used immunohistochemistry to detect the expression of SPP1 protein and immune cell related proteins in penile cancer tissue. Then, we performed weighted gene coexpression network analysis (WGCNA) to identify the genes related to SPP1 in penile cancer tissue and positive lymph node tissue. Based on the GSE57955 dataset, the CIBERSORT and ssGSEA algorithms were carried out to investigate the immune environment of PSCC. GSVA analysis was conducted to identify the signaling pathways related to SPP1 subgroups. Enzyme-linked immunosorbent assay (ELISA) method was adopted to detect SPP1 level in the serum of 60 patients with penile cancer.
RESULTS
Differential analysis indicated that SPP1 was the most differentially upregulated gene in both penile cancer tissues and positive lymph node tissues. Survival analysis suggested that the prognosis of the low-SPP1 group was significantly poorer than that of the high-SPP1 group. Subsequently, immune-related bioinformatics showed that SPP1 was significantly associated with B cells, CD8 + T cells, CD4 + T cells, macrophages, helper T cells, neutrophils and dendritic cells. The immunohistochemical results showed that the high-SPP1 group was characterized by relatively high expression of CD16 and relatively low expression of CD4. GSVA analysis indicated that high-SPP1 group was significantly associated with immune-related pathways such as PD-L1 expression and the PD-1 checkpoint pathway in cancer and the TNF signaling pathway. ELISA demonstrated that the serum level of SPP1 in patients with positive lymph node metastasis of penile cancer was significantly higher than that in patients with negative lymph node metastasis of penile cancer.
CONCLUSION
Our study shows that the SPP1 gene might be an effective biomarker for predicting the prognosis and the efficacy of immunotherapy in PSCC patients.
Topics: Carcinoma, Squamous Cell; Penile Neoplasms; Immunotherapy; Osteopontin; Biomarkers, Tumor; Gene Expression Profiling; Survival Analysis; Sequence Analysis, RNA
PubMed: 38111044
DOI: 10.1186/s40246-023-00558-5 -
Virchows Archiv : An International... Dec 2023The classification of the epithelial tumors of the male and female urethra includes benign and malignant neoplasms. Primary urethral carcinomas and adenocarcinomas of... (Review)
Review
The classification of the epithelial tumors of the male and female urethra includes benign and malignant neoplasms. Primary urethral carcinomas and adenocarcinomas of the accessory glands are the most relevant tumors, both from the morphologic and clinical point of view. An accurate diagnosis, grading and staging are essential for determining adequate treatment strategies and outcome. Information on anatomy and histology of the urethra is of fundamental importance in understanding the morphology of the tumors, including the clinical importance of their location and origin.
Topics: Humans; Male; Female; Urethra; Adenocarcinoma; Biomarkers, Tumor; Urethral Neoplasms
PubMed: 37233807
DOI: 10.1007/s00428-023-03565-y -
Cureus Mar 2024Background Penile cancer is a rare malignancy usually requiring surgery to achieve oncological control of the primary tumour but often at the expense of functional...
Background Penile cancer is a rare malignancy usually requiring surgery to achieve oncological control of the primary tumour but often at the expense of functional length. The presenting stage of the primary is a crucial factor in determining the most appropriate surgical procedure. Accurate preoperative staging is essential, and current modalities include clinical and radiological assessment. Clinical staging can, however, be hampered by patient body habitus and unreliable for more advanced T4 tumours, whereas radiological staging allows for more detailed identification of tissue planes and tumour involvement. There is no clear consensus on the preferred imaging technique, although, in the current European Association of Urology penile cancer guidelines, MRI is recommended with the use of ultrasound when MRI is not available. It was recommended that having the penis in an erect state by the administration of intra-cavernosal prostaglandin gave a more detailed picture enabling a greater predictor of corporal involvement. Recent studies have, however, suggested that there may be no such advantage. Methodology A retrospective review was conducted of all patients who underwent surgery for penile cancer comparing the preoperative MRI stage with the final pathological stage between July 2009 and June 2023. In addition to the MRI, patients were given an intra-cavernosal injection of prostaglandin E1 to induce tumescence unless otherwise indicated. All imaging was reported by a single consultant uro-radiologist with surgery undertaken by a single surgeon and pathology reviewed through the supra-regional penile multidisciplinary team. Results A total of 136 penile cancer patients were included in the review. Within this cohort, 98 patients had an MRI without intra-cavernosal prostaglandin and the number who had Ta, T1, T2, T3 and T4 histopathological stages was 3, 31, 45, 18, and 1, respectively. The preoperative MRI stage had a low agreement with the final histological stage for early tumours, with sensitivities and specificity of 35% and 97% for T1 and 56% and 80% for T2, respectively. Sensitivity and specificity increased for cavernosal involvement at 83% and 95%, respectively. In addition, a further 38 patients had an MRI in conjunction with an injection of prostaglandin E1 which failed to show any diagnostic improvement in sensitivity or specificity in the preoperative MRI stage. Conclusions The use of MRI as a preoperative modality for staging penile cancer performs best for identifying tumour involvement of the cavernosal bodies. Performing the MRI with the penis erect with the use of an intra-cavernosal injection did not offer any additional benefit in accurately staging penile cancer.
PubMed: 38606225
DOI: 10.7759/cureus.56016 -
Iranian Journal of Pathology 2024Penile squamous cell carcinoma (SCC) is an extremely rare malignancy. It is usually caused by chronic human papillomavirus (HPV) 16 and HPV 18 infections. This study was...
BACKGROUND & OBJECTIVE
Penile squamous cell carcinoma (SCC) is an extremely rare malignancy. It is usually caused by chronic human papillomavirus (HPV) 16 and HPV 18 infections. This study was conducted to investigate the immunohistochemical overexpression of p16, a surrogate marker for HPV, and to evaluate its usefulness as a potential diagnostic biomarker.
METHODS
In this cross-sectional prospective and retrospective cohort study, 56 penile squamous cell carcinoma (SCC) specimens and five penile premalignant specimens were evaluated in Kasturba Medical College, Mangalore, India, from January 2013- December 2018 in terms of clinical and histopathological features. Immunohistochemical expression for p16 in cases and controls was evaluated. Statistical comparison of p16 expression among clinical features, histological subtype, grade, and stages of tumor were done.
RESULTS
Analysis of the pattern of p16 staining showed diffuse and strong nuclear and cytoplasmic expression in 32.8% of the cases. There was a highly significant association (<0.001) of pattern of p16 expression among the HPV and non-HPV subtypes of penile carcinoma. p16 expression was not significantly associated with other prognostic parameters like site of the lesion, lymphovascular invasion, perineural invasion, histologic grade, and pathologic stage.
CONCLUSION
Expression of p16 would be a useful tool in differentiation between the HPV-associated and non-HPV-associated subtypes of penile SCC that may be helpful in prediction of aggressiveness and invasive potential of the respective histologic subtypes.
PubMed: 38864076
DOI: 10.30699/IJP.2024.1998898.3092