Penile cancer is a rare disease in the United States, but rates are increasing, causing concern. Several risk factors have been associated with the disease, including human papillomavirus (HPV) infection. Knowledge of HPV pathogenesis has led to the development of a vaccine, which has proven instrumental in reducing the incidence of female HPV-related cancers, but results in men have yet to be elucidated. Fortunately, rates of vaccination are up-trending in both males and females in the past several years. In addition, targeted therapies are the focus of several ongoing research efforts. Some of these therapeutics are currently in use, while several are in trials. With continued patient education and research, both treatment and prevention of HPV-related pre-malignant lesions and penile cancer will likely diminish.

Stress elicits activation of the hypothalamic-pituitary-adrenal axis, which leads to enhanced circulating glucocorticoids, as well as impaired gonadotropin secretion and ovarian cyclicity. Here, we tested the hypothesis that elevated, stress-levels of glucocorticoids disrupt ovarian cyclicity by interfering with the preovulatory sequence of endocrine events necessary for the LH surge. Ovarian cyclicity was monitored in female mice implanted with a cholesterol or corticosterone (Cort) pellet. Cort, but not cholesterol, arrested cyclicity in diestrus. Subsequent studies focused on the mechanism whereby Cort stalled the preovulatory sequence by assessing responsiveness to the positive feedback estradiol signal. Ovariectomized mice were treated with an LH surge-inducing estradiol implant, as well as Cort or cholesterol, and assessed several days later for LH levels on the evening of the anticipated surge. All cholesterol females showed a clear LH surge. At the time of the anticipated surge, LH levels were undetectable in Cort-treated females. In situ hybridization analyses the anteroventral periventricular nucleus revealed that Cort robustly suppressed the percentage of Kiss1 cells coexpressing cfos, as well as reduced the number of Kiss1 cells and amount of Kiss1 mRNA per cell, compared with expression in control brains. In addition, Cort blunted pituitary expression of the genes encoding the GnRH receptor and LHβ, indicating inhibition of gonadotropes during the blockage of the LH surge. Collectively, our findings support the hypothesis that physiological stress-levels of Cort disrupts ovarian cyclicity, in part, through disruption of positive feedback mechanisms at both the hypothalamic and pituitary levels which are necessary for generation of the preovulatory LH surge.

Penile cancer (PeCa) is a rare malignancy with potentially devastating effects. Squamous cell carcinoma is the most common variant with distinct precancerous lesions before development into invasive disease. Involvement of the inguinal lymph nodes is the most important prognostic factor in PeCa, and once disease is present outside the groin, prognosis is poor. Metastatic PeCa is challenging to treat and often requires multidisciplinary approaches in management. Due to its rarity, molecular understanding of the disease continues to be limited with most studies based on small, single center series. Thus far, it appears PeCa has diverse mechanisms of carcinogenesis affecting similar molecular pathways. In this review, we evaluate the current landscape of the molecular carcinogenesis of PeCa and explore ongoing research on potential actionable targets of therapy. The emergence of anti-epidermal growth factor receptor (EGFR) and other immunotherapeutic strategies may improve outcomes for PeCa patients.

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