In this prospective study we are reporting the socioeconomic profile, presence of risk factors, sexual history, tumor morphologic features, and HPV status of patients with penile carcinomas. The epidemiological characteristics are those already described in other studies [14
]. The majority of penile cancer patients in Paraguay were from rural or suburban areas. This represents a demographic change considering that, in a previous report from the 1960’s, most patients lived in rural regions [17
]. This shift might be related to a recent significant migration from rural to suburban areas. However, suburban people, unlike their counterparts in developed nations, live under harsh conditions and are culturally and socioeconomically underserved, similar to rural patients. In countries where 20% or more of the population live in poverty, such is the case in Paraguay, the risk for penile cancer is 43% higher than in countries with less than 10% poverty levels [16
The majority of our patients (76%) were heavy smokers. There is a clear dose response relation of smoking with penile cancer. Previous studies have shown that patients smoking more than 10 cigarettes per day, as the majority of our patients, had a significantly higher risk than light smokers [14
]. In a recent series, Koifman et al [18
] also found a high incidence of smoking among Brazilian penile cancer patients (56.5%). Nevertheless, the exact mechanisms and precise role that smoking plays in penile cancer development is largely unknown.
The “foreskin factor” is important in penile cancer oncogenesis since there is strong evidence that circumcision at birth, as it is ritually practiced in the Jewish, Muslin, and other populations, prevents its occurrence [3
]. Most of the Paraguayan patients in this study were uncircumcised. The few individuals reporting a history of previous circumcision (10%) had the procedure performed within the context of a symptomatic medical condition. Circumcision was also uncommon in Brazilian patients, according to Koifman et al [18
]. Some studies suggest that circumcision practiced at adulthood, even in those cases done by religious or cultural reasons, instead of protecting against, is associated with an increased risk of penile cancer, especially when extensive scaring develops [19
]. A possible explanation for this seemly contradictory phenomenon could be related to the development of the scar itself or to the presence of subclinical penile lesions at the time of the procedure.
The protective effect of newborn circumcision is probably linked to the prevention of phimosis [3
]. In an early study, Hellberg et al reported a relative risk of 64.6 for penile cancer among men with phimosis [20
]. Following this study, several others have confirmed the role of phimosis as a risk factor for tumor development [14
]. The high prevalence of difficulty in retracting the foreskin we found (57%) is similar to the figures reported in Northeastern Brazil by Favorito et al [21
]. A frequent association of phimosis with lichen sclerosus in our series (74%) suggests a causal link. Other interesting findings were those related to the sexual history of patients with penile cancer. As an unadjusted covariate, patients with a sexual history of > 10 lifetime female partners were more prone to present HPV positive tumors. A similar trend has been reported in women in regards to the risk of cervical carcinomas [22
One possible limitation of the present study is the lack of an age-matched control group for patients with penile cancer. However, this study was designed to explore the association of pathologic features of penile tumors with clinical and epidemiologic features of the targeted population. We did not aim to identify or evaluate risk factors for the development of penile cancer in the general population. In this sense, we built upon previously recognized risk factors, such as smoking, foreskin features, circumcision status, and sexual history [3
]. Studies with similar designs to our design are scant, especially from regions of high prevalence. Our results could help unravel the complex pathogenesis of penile cancer and contribute in the understanding of its differential distribution across different geographical regions.
In summary, we have described the epidemiological, clinical, and pathological profile of patients with penile SCC in Paraguay, a geographical region with one of the highest rates in penile cancer. Patients usually lived in rural/suburban areas, in poverty, and had a low education level. Most of them were heavy smokers. Circumcision was uncommon and, when practiced, was related to the presence of medical conditions. Long foreskins and moderate/poor genital hygienic habits were also frequently found, as well as a high reported history of sexually transmitted diseases. HPV-related tumors were characterized by a warty and/or basaloid morphology, high histological grade, and association with precursor lesions showing similar features to their invasive counterparts while HPV negative tumors were well to moderately differentiated SCC, frequently associated with lichen sclerosus and differentiated PeIN. These data might help in the development of strategies for penile cancer control in Paraguay.