Prevalence of human papillomavirus in penile malignant tumors: viral genotyping and clinical aspects

Tumor biopsies of penile cancer were evaluated in 76 patients aged 26 to 97 years with a mean of 60.7 years and standard deviation of ±17.10, presenting a higher prevalence in the over 66 age group. The clinical representation and pathologic characteristics distribution is shown on Table 1.

These results correspond with those obtained in the literature [10-14]. The average age of the patients at diagnosis predominates in advanced age (>50 years), which suggests that men seek health services very late in life [15]. Younger individuals are also affected, but in smaller percentages [7].

Regarding the location of the lesions, the glans, in an isolated form or associated with other regions, was the most affected structure as in the research by Delgado et al. [10], Wanick et al. [11] and Favorito et al. [8].

Studies have shown that the lesions on the glans are directly linked to poor hygiene. This occurs due to the formation of a mass, called smegma, followed by likely irritation of the site and onset of injury, facilitating various infections and future neoplasia if left untreated [10].

Regarding the clinical morphology, the predominantly found lesion was the vegetating type followed by ulceration. The occurrence of both types of lesions in the same patient was observed in 22.37% of the cases. In a study performed in Spain, researchers observed that the vegetative lesion was also more present, in 66% of the cases [12]. On the other hand, in another research conducted in Rio de Janeiro [10], a larger number of lesions was detected in the form of ulcerations, nearly 55.88% of the studied cases.

The dimensions of the lesions were similar to those observed in the Wanick et al. results [10], with a larger number of cases: 52.63% of the cases, with size between 2.1 and 5.0 cm.

Unlike other studies, the moderately differentiated tumors (grade II) identified in this work, according to Broder’s classification, were the most prevalent. Fonseca et al. [13] identified a greater number of cases classified as well differentiated (grade I). However, Scheiner et al. [14] observed higher incidence of grade III (undifferentiated) tumors, which can be explained by the greater presence of stage III and IV patients.

The findings indicated that invasion was present in 23.68%, and infiltration occurred in at least one of the structures, with the highest prevalence in the corpus cavernosum. Koifman et al. [15] reported the presence of invasion of the spongiosum or cavernous corpus in 41.3% of the patients.

Regarding lymph node involvement, a percentage of 19.73% was observed. According to Sacoto et al. [12], patients with more advanced disease and positive lymph nodes at the time of diagnosis had a worse survival rate than those with localized stages.

The DNA of the HPV was detected in 63.15% (48/76) of the samples. The oncogenic risk distribution is shown on Table 2. This percentage is within the range reported in the literature, which shows that the rate of HPV infection in penile malignant tumors may vary from 20 to over 75% of cases [16]. According to a systematic review of the prevalence of HPV in invasive tumors of the penis, 48% of the samples presented HPV infection [17]. A Belgian study by D’Hauwers et al. [18], which had the same number of patients as in this study, revealed that 70.9% of the tumors had the HPV virus. However, a survey conducted in Vietnam demonstrated that only 23% of tumors had HPV infection [19]. A study conducted in Brazil showed that 75% of invasive penile tumors were infected by HPV [14]. These variations may be due to different techniques used for viral detection, regional differences or histological type of the analyzed tumor.

In our study, among the high-risk viral types present were the 16, 18, 45 and 69 types. The HPV of type 11 was the only low oncogenic risk found. Type 16 was the most prevalent, found in 10 cases, followed by type 11 of low risk with 6 cases, type 18 with 4 cases, type 69 with two cases and type 45 with 1 case. The automated sequencing technique was not effective for viral genotyping, because in more than 50% of the samples it was not possible to achieve. This may be due to the presence of co-infections in these samples, which prevents the device from detecting the virus, as described by Gharizadeh et al. (2005) and Verteramo et al. (2009) [20,21]. The most common viral type found in this study was HPV 16, high-risk type. This virus type was also the most found in other studies such as those developed by Do et al. [19] (89%), D’Hauwers et al. [18] (48.3%) and Heidman et al. [16] in (52%).

As shown in Table 3, no association was found (p < 0.05) between infection with HPV virus and clinical and histopathological and clinical variables, as was the case in the research by Do et al. [19], Fonseca et al. [22] and Scheiner et al. [14].

Infections by HPV are strongly associated with the development of penile cancer; however, the role of viruses in the etiology is not very clear [21]. Although the etiology is still unknown, approximately 40% of all penile tumors are related to HPV infection [22].