Clinical Epidemiologic Study of Penile Cancer in the State of Pernambuco, Brazil

ABSTRACT

Introduction: Penile cancer is a malignant disease that has an uneven geographical distribution. Brazil is one of the countries with the highest incidence of penile cancer, although epidemiological studies are rare. Poor hygiene, the presence of phimosis, HPV infection, and low socioeconomic status seem to be some important risk factors. The objective of this study is to know the clinical and epidemiological data on new cases of penile cancer in the state of Pernambuco, located in the northeast region of Brazil, and contribute to the national study of the Brazilian Society of Urology.

Methods: We selected from a plethora of new penile cancer cases diagnosed from August 2008 to June 2009, at the department of urology of 5 referral hospitals of the National Health System. Interviews were conducted with a clinical, epidemiological questionnaire adapted from the questionnaire used by the SBU in the first epidemiological study of penile cancer. All patients gave written, informed consent for inclusion in the sample. This study was approved by the ethics committees of the institutions involved.

Results: In 11 months of the study, 32 new cases of penile cancer were enrolled and analyzed in 5 referral hospitals in Pernambuco. The average age of lesion diagnosis was 59.2 years (SD ± 14.3 years), with 50% of cases diagnosed in patients over 60 years. Regarding schooling, 92% were illiterate or had only a primary level of schooling, and none advanced beyond the second grade. Assessing the antecedents and habits, it was found that 8 patients (32%) had at least 1 case of a lifelong STD, 14 patients (56%) reported a history of phimosis, and only 4 (16%) underwent circumcision, 3 of which during adulthood. Smoking was an addiction reported by 56.2% of patients. The average time between the appearance of the lesion and the diagnosis of penile cancer was higher than 10 months.

Conclusion: Penile cancer in referral hospitals of Pernambuco usually involves men older than 60 years, with low education, a history of smoking, uncircumcised genitalia, and with delayed access to specialized medical care. It is necessary to create campaigns for the prevention and guidance of this most affected population.

KEYWORDS: Circumcision; Epidemiology; Penile cancer; Phimosis; Risk factors

CORRESPONDENCE: Marina de Andrade Lima Arcoverde, Federal University of Pernambuco, Recife, Brazil ().

CITATION: UroToday Int J. 2012 Feb;5(1):art 91. http://dx.doi.org/10.3834/uij.1944-5784.2012.02.09

INTRODUCTION

Penile cancer is a malignant disease that has a curiously uneven geographical distribution [1]. In Europe, the incidence is rare, and varies between 0.1 and 0.9 per 100 000 males. In the US, it varies between 0.7 and 0.9 per 100 000 males. However, the incidence of penile cancer is significantly higher when dealing with developing countries in regions such as Africa, Asia, and South America, where it can reach 20 per 100 000 males [2]. In these countries, penile cancer remains a major public health issue since it represents 10 to 20% of all malignancies in men [2].

Penile cancer represents approximately 2% of all cancers in males in Brazil, with most cases reported in the north and the northeast regions [3]. In these areas, penile carcinoma outnumbers, in some states, even the cases of prostate and bladder cancer [4]. Although the etiology of cancer is unknown, poor hygiene, the presence of phimosis, HPV infection, and low socioeconomic status are known risk factors [5]. Age is one of the main risk factors while ethnicity is not [6,7].

Phimosis is present in 75 to 90% of penile cancer cases [8]. The incidence of penile cancer is extremely low, reaching less than 1 percent of all diagnosed cancers, in countries where circumcision is a common practice [6]. The prophylactic effect of circumcision in penile carcinoma appears to be related to less retention of the smegma that has, arguably, a carcinogenic and inflammatory effect in animals [9].

Another factor that may predispose the development of penile carcinoma is HPV infection. In some reports, the association between penile cancer and HPV reaches over 30% of the patients, revealing the oncogenic effect of the virus, also in men [7,10]. Other skin lesions, such as Queirat erythroplasia, Bowen’s disease, and balanitis xerotic, can also develop into squamous cell carcinoma (SCC) in the penile region [11], the first 2 already considered by some authors as carcinoma in situ since they are composed of dysplastic characteristic cells [12].

Some studies reveal that SCC is the most common type of penile cancer, accounting for more than 95% of the cases [11,23]. Penile cancer primarily spreads through the lymphatic system. Inguinal lymph nodes are usually the first site of metastasis [11]. The treatment is mainly surgical, which may be a simple resection, partial, or complete amputation and emasculation [6].

Recife, the capital of Pernambuco, has a penile cancer incidence of 6.8/100 000 [13], which is higher than American and European rates, but quite similar to both north and northeast regions of Brazil where this type of cancer is mostly located [3]. Therefore, the primary objective of this study is to analyze the clinical and epidemiological profile of penile cancer in Pernambuco, contributing to the Brazilian epidemiological tracing initiated by the Brazilian Society of Urology, and also to prove the under-reported cases of penile cancer in the state in Pernambuco in that previous study. The outcome data, such as disease-specific survival rate, type of surgery performed, and functional outcomes, does not meet the interest of this work.

METHODS

This work was carried out in Pernambuco State, located in the northeast region of Brazil, through a multicenter study conducted in 5 referral hospitals, for the treatment of urological cancer in the state; all 5 were part of the National Health System.

We studied every new case of penile carcinoma diagnosed and admitted in the urology services of these institutions, from August 2008 to June 2009, representing a total of 32 patients. We excluded from the study all patients diagnosed with disease at a stage of premalignancy, those with inconclusive histopathological examinations, as well as those who refused to participate. The hospitals’ protocols on penile cancer were followed properly.

Through an interview with the selected patients, we filled out a clinical, epidemiological questionnaire, adapted from the questionnaire used by the Brazilian Society of Urology in the first epidemiological study of penile cancer [3].

The variables in the questionnaire were age, education level, a history of STD or preneoplastic disease, a partner with a history of HPV infection or cervical cancer, smoking, a history of phimosis and/or performing circumcision, the time between the appearance of the lesion and the diagnosis, site of the lesion, and histology.

Age was a categorical factor in this research, divided by decades of life. Schooling was divided into illiterate, primary education (elementary and middle school), secondary education (high school), and tertiary education (college and university). For patients who underwent circumcision, it was classified according to when the surgery took place(childhood, adolescence, or adulthood). The lesion was classified according to the involvement of the region, such as glans; foreskin; shaft; base; glans and foreskin; glans, foreskin, and shaft; or the entire penis. According to the histological differentiation, the lesions were classified between grades I, II, III, and IV, the last being the greatest degree of undifferentiation.

The results were analyzed with descriptive statistics and frequencies using the program BioEstat 5.0 for Windows. This work was approved by the ethics committees of all the institutions involved, and all patients gave written, informed consent for inclusion in the sample.

RESULTS

In 11 months of the study, 32 new cases of penile cancer were admitted to referral hospitals in Pernambuco, of which 16 (50%) were registered in the Cancer Hospital of Pernambuco.

The average age of affected patients was 59 years (SD ± 14.9 years), and the highest prevalence was found between the ages of 41 and 70 years old, representing a total of 71.9% of cases (Figure 1). Regarding schooling, 91% of patients were illiterate or had only studied until primary school. Those who had dropped out of school during the course of primary or secondary education were also included in these categories. None of the respondents had initiated tertiary education.

During evaluation of background and personal habits, it was found that 11 patients (33%) had had at least 1 case of STDs throughout life. One of the patients had a prior diagnosis of preneoplastic disease (3.1%), and 3 others had been diagnosed with condylomatosis (9.4%). Only 1 patient reported a partner with a previous HPV infection (Figure 2).

Nineteen patients (59.4%) reported a history of phimosis, of which only 4 (12.5%) were circumcised. Smoking was an addiction reported by 56.2% of patients, with an average of 29.3 years of addiction for patients who smoke.

Regarding diagnosis, the average time between the appearance of the lesion and the diagnosis of penile cancer was 10.8 months (SD ± 2.08 months), and the sizes of the lesions ranged from 0.7 to 10 cm, with an average 4.08 cm lesion. The most affected areas were the glans and/or the prepuce, representing a total 71.8% of cases.

The predominant histologic type was well differentiated SCC (lesions I) found in 26 patients (81.25%), followed by the pattern of moderately differentiated cell carcinoma (lesions II) in 2 patients (9.4%). Only 1 case had a diagnosis of mucoepidermoid carcinoma. Another patient had a histopathological diagnosis of papillary hyperplasia, as well differentiated SCC, when the previous biopsy was diagnosed. A single patient had grade IV injury, with the presence of undifferentiated cells.

In surgical treatment, there were 21 partial penectomies (65.6%), 10 total penectomies (31.3%), and 1 circumcision (3.1%).

DISCUSSION

Brazil is one of the countries with the highest incidence of penile cancer in the world, and even then, epidemiological studies are rare. Recently, the Brazilian Society of Urology (SBU) conducted a national study on penile cancer, aiming to outline an epidemiological profile of the disease in the country [3] and adopt preventive, diagnostic, and prophylactic measures. In that study, Pernambuco contributed with only 1 case, for a total of 110 reported cases in 6 months across the country. Our research demonstrates that the occurrence of penile cancer in the state of Pernambuco is much higher, making it clear that they were underreported since there is notification of 32 new cases in 11 months.

Penile cancer occurs more frequently in men after the sixth decade of life [6]. In the current sample, 50% of patients were over 60 years. Of the total cases analyzed, only 1 (3.1%) was aged 35 years, this incidence being significantly lower than the 10% reported by Nardi [3]. On the other hand, a high prevalence of penile cancer was noticed among the age group between 41 to 60 years, representing 43.8% of the total. This emphasizes the importance of close monitoring of nonelderly patients with suspicious penile lesions.

The low socioeconomic cultural status is closely related to poor genital hygiene, and both are important factors in the development of the disease [13]. The level of schooling in this study was used as a socioeconomic status meter and revealed that over 90% of patients had not exceeded the level of primary education. Since the northeast still has an illiteracy rate of 18.7% [14], and one of the lowest incomes per capita in Brazil, it is expected that this region contributes to a large portion of total penile cancer in the country, which, according to the Brazilian Society of Urology, corresponds to 40% [3]. There is evidence that lack of hygiene in the genital region makes the individual more vulnerable to HPV infection, this being one of the links between poor hygiene and penile cancer. On the other hand, it is notable that the socioeconomic-cultural status interferes in the time between the onset of the lesion and the diagnosis, since people with low purchasing power have greater difficulties accessing specialists, and they usually rely on alternatives or popular therapies without proven effect.

Although the mechanism of action of HPV and other STDs in the formation of oncogenic cells is not fully elucidated, some studies show a strong association between them [15]. HPV seems to act by altering the cell cycle by the expression of viral proteins that interact with cellular proteins. These cellular proteins disrupt the strict cell-cycle control by tumor suppressing genes, which turns the infection into a strong precursor of tumors [7]. In our study, 34% of patients (n = 11) reported previous cases of unspecified STDs, while another 12.5% did not answer the question. Additionally, 9.4% of interviewed patients (n = 3) reported the presence of condylomatous lesions in the penis. In a study published in 2008, HPV-positive DNA was detected in 72% cases of penile carcinoma patients with squamous cell, while in another study, the association between penile cancer and HPV infection was 30.5% [16]. It is important to remember that the data collected in our research was not confirmed by laboratory tests, but still indicates the importance of sexually transmitted diseases as a risk factor for penile cancer. Furthermore, due to the low social-intellectual level of the patients, the use of a written questionnaire made it difficult to learn precise information about previous HPV infection, although, at the time, no patients had active HPV lesions.

Another identified risk factor was the presence of phimosis, found in 59.4% of our cases. Studies report that phimosis, as well as chronic inflammation of the glans, increases the odds of developing penile cancer by 10 [17]. In turn, the practice of circumcision is a good way to prevent the neoplasm since it is performed soon after birth, decreasing the risk of developing the pathology by 3 [18]; however, when performed later in adulthood, it does not offer the same protection [5]. In our study, 4 patients had undergone circumcision as adults, and even then, the tumor took place, which agrees with the literature. Although there is no data showing the relationship between personal hygiene, phimosis, and penile cancer, some scholars believe that good hygiene is the key to preventing both the development of phimosis and the tumor once they are strictly related [2,19,20].

It was observed that 56.2% (n = 18) of patients in this study were smokers, and 72.3% (n = 13) had smoked for more than 20 years. According to a study by Daling et al., male smokers are more likely to develop invasive penile carcinoma [21]. Another study argues that the incidence of penile cancer is 2.4 times greater for those who are or were smokers, with the largest number found in the group of men that smoked more than 20 cigarettes per day [22]. There are suspicions that the same way that nicotine accumulates in the secretion of the cervix in women smokers could accumulate in the secretions of the penis, developing its carcinogenic effect in the region [23]. It is noted, therefore, that smoking, along with the presence of phimosis, is presented as an extremely important risk factor for penile cancer.

The average time between the appearance of the lesion and the diagnosis exceeded 10 months, which is an alarming number. It reveals the patient’s difficulty in accessing a specialist. This number may also result from the ignorance of the population and its fear of surgical treatment. This delay in diagnosis radically affects the treatment of the disease, and usually leaves mutilating surgery as the only viable treatment. In 65.5% of the patients, partial penectomy was performed. Total penectomy was performed in 31.3% of the patients, and only 1 patient (3.1%) was treated with circumcision. Therefore, early diagnosis is of great importance for a better resolution of the disease. It may also avoid radical surgery and its physical, psychological, and sexual impact.

CONCLUSION

This study found an epidemiological pattern of penile cancer in the state of Pernambuco was similar to that observed in the rest of the country, with a higher prevalence of penile cancer among men after the sixth decade of life, with a low education level, with an uncircumcised penis, a history of smoking, and those who do not seek medical care immediately. These findings show the immediate necessity to create a national campaign for prevention and guidance of matters regarding penile cancer, particularly for the low-income male population, which is the most affected class.

REFERENCES

Barbosa Júnior AA, Athanázio PR, Oliveira B. [Cancer of the penis: study of its geographic pathology in the State of Bahia, Brazil]. Rev Saúde Pública. 1984;18(6):429-435.

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