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Should routine neonatal circumcision be a policy to prevent penile cancer? | Opinion: No

prevention and control [Subheading]; Circumcision, Male; Penile Neoplasms; Phimosis

Routine neonatal circumcision remains a controversial topic. The most recent Canadian Paediatric Society does not recommend routine circumcision of every newborn male (11. Sorokan ST, Finlay JC, Jefferies AL; Canadian Paediatric Society, Fetus and Newborn Committee, Infectious Diseases and Immunization Committee. Newborn male circumcision. Paediatr Child Health. 2015;20:311-20.). And although prior statements from the American Academy of Pediatrics recommended against circumcision, the most recent recommendation states that circumcision outweigh the risk and the procedure’s benefits justify it for families who want it (22. American Academy of Pediatrics Task Force on Circumcision. Circumcision policy statement. Pediatrics. 2012;130:585-6.). The benefits mentioned by the American Academy of Pediatrics included prevention of urinary tract infections, transmission of sexually transmitted infections, and penile cancer. Prevention of penile cancer may be related to increasing daily hygiene and decreasing sexually transmitted infections such as human papilloma virus (HPV) in circumcised males. However, with improvements in daily hygiene and sexually transmitted infection prevention strategies, neonatal circumcision may not be critical for the prevention of penile cancer, especially in western countries.

The association between lack of circumcision and penile cancer has been well documented (33. Larke NL, Thomas SL, Santos Silva I dos, Weiss HA. Male circumcision and penile cancer: a systematic review and meta-analysis. Cancer Causes Control. 2011;22:1097-110.). A meta-analysis found a strong protective effect of childhood circumcision on invasive penile cancer in 3 studies (OR 0.33; 95% 0.13-0.83) (33. Larke NL, Thomas SL, Santos Silva I dos, Weiss HA. Male circumcision and penile cancer: a systematic review and meta-analysis. Cancer Causes Control. 2011;22:1097-110.). However, in other studies when analyses were restricted to boys without a history of phimosis, the meta-analysis found that the protective effect of childhood circumcision on invasive disease no longer persisted (33. Larke NL, Thomas SL, Santos Silva I dos, Weiss HA. Male circumcision and penile cancer: a systematic review and meta-analysis. Cancer Causes Control. 2011;22:1097-110.). In addition, penile cancer continues to be one of the rarer malignancies in the world. In the United States where circumcision is prevalent, the rarity of disease is highlighted by its decreasing incidence. An analysis from the Surveillance, Epidemiology and End Results (SEER) database showed that the penile cancer incidence decreased to 0.58 per 100,000 in 1993-2002 from 0.84 per 100,000 in 1973-1982 in the United States (44. Barnholtz-Sloan JS, Maldonado JL, Pow-sang J, Giuliano AR. Incidence trends in primary malignant penile cancer. Urol Oncol. 2007;25:361-7. Erratum in: Urol Oncol. 2008;26:112.). However, there is also a similar trend in countries with low circumcision rates such as Denmark and Finland (55. Frisch M, Friis S, Kjaer SK, Melbye M. Falling incidence of penis cancer in na uncircumcised population (Denmark 1943-90). BMJ. 1995;311:1471., 66. Maiche AG. Epidemiological aspects of cancer of the penis in Finland. Eur J Cancer Prev. 1992;1:153-8.). In Denmark, penile cancer risk decreased from 1.15 per 100,000 in the 1940s to 0.82 per 100,000 in the late 1980s (55. Frisch M, Friis S, Kjaer SK, Melbye M. Falling incidence of penis cancer in na uncircumcised population (Denmark 1943-90). BMJ. 1995;311:1471.). Finland reported an incidence rate of 0.5 per 100,000 (66. Maiche AG. Epidemiological aspects of cancer of the penis in Finland. Eur J Cancer Prev. 1992;1:153-8.). Coupled with the rarity of penile cancer and conflicting evidence in the literature, it is hard to justify routine neonatal circumcision for all healthy males, including those without any preputial abnormalities, solely for the prevention of penile cancer.

Despite its rarity, there are several common factors that have been implicated to cause penile cancer. Factors resulting in phimosis, balanitis, and smegma have been associated with penile cancer in a meta-analysis (77. Morris BJ, Gray RH, Castellsague X, Bosch FX, Halperin DT, Waskett JH, et al. The Strong Protective Effect of Circumcision against Cancer of the Penis. Adv Urol. 2011;2011:812368.). This has often been attributed to the lack of circumcision and poor hygiene as a major risk factor in developing these inflammatory conditions. However, with improved daily hygiene, these conditions can still be combatted even with a lack of circumcision. For example, in the Denmark population where there is only a 2% circumcision rate, the incidence of penile cancer was shown to be steadily declining, likely coinciding with an increase in indoor bathrooms and improved hygiene (55. Frisch M, Friis S, Kjaer SK, Melbye M. Falling incidence of penis cancer in na uncircumcised population (Denmark 1943-90). BMJ. 1995;311:1471.). However, it’s notable that the most recent study of the same population found an increasing rate of penile cancer from 1978 to 2008 (88. Baldur-Felskov B, Hannibal CG, Munk C, Kjaer SK. Increased incidence of penile cancer and high-grade penile intraepithelial neoplasia in Denmark 1978-2008: a nationwide population-based study. Cancer Causes Control. 2012;23:273-80.). This study reported an average annual percentage change of 0.8% in incidence resulting in an increase in incidence to 1.3 per 100,000 men in 2008. Although this study did not contain data regarding HPV status, the prevalence of HPV in Denmark has also been found to be as high as 33-45% of men in several reports (99. Svare EI, Kjaer SK, Worm AM, Osterlind A, Meijer CJ, Brule AJ van den. Risk factors for genital HPV DNA in men resemble those found in women: a study of male attendees at a Danish STD clinic. Sex Transm Infect. 2002;78:215-8., 1010. Kjaer SK, Munk C, Winther JF, Jørgensen HO, Meijer CJ, Brule AJ van den. Acquisition and persistence of human papillomavirus infection in younger men: a prospective follow-up study among Danish soldiers. Cancer Epidemiol Biomarkers Prev. 2005;14:1528-33..). In addition, several studies have shown an increase in HPV-associated cancers in Denmark over a similar time period (1111. Nielsen A, Munk C, Kjaer SK. Trends in incidence of anal cancer and high-grade anal intraepithelial neoplasia in Denmark, 1978-2008. Int J Cancer. 2012;130:1168-73., 1212. Baandrup L, Varbo A, Munk C, Johansen C, Frisch M, Kjaer SK. In situ and invasive squamous cell carcinoma of the vulva in Denmark 1978-2007-a Nationwide population-based study. Gynecol Oncol. 2011;122:45-9.). Therefore, it is unlikely that an increase in penile cancer incidence can solely be explained by a low circumcision rate. Rather, it may be the HPV associated penile carcinogenesis that plays a larger factor in disease incidence in this cohort.

As a driving factor for penile carcinogenesis, the prevalence of HPV induced penile cancer has been shown to be approximately 50% of penile malignancies worldwide (1313. Backes DM, Kurman RJ, Pimenta JM, Smith JS. Systematic review of human papillomavirus prevalence in invasive penile cancer. Cancer Causes Control. 2009;20:449-57.). Circumcision has also been known to play a role in the prevention of sexually transmitted diseases such as HPV. In addition, the association between circumcision and reduced risk of penile HPV has been well documented in several randomized clinical trials and meta-analyses (1414. Castellsagué X, Albero G, Clèries R, Bosch FX. HPV and circumcision: a biased, inaccurate and misleading meta-analysis. J Infect. 2007;55:91-3.

15. Tobian AA, Serwadda D, Quinn TC, Kigozi G, Gravitt PE, Laeyendecker O, et al. Male circumcision for the prevention of HSV-2 and HPV infections and syphilis. N Engl J Med. 2009;360:1298-309.
-1616. Serwadda D, Wawer MJ, Makumbi F, Kong X, Kigozi G, Gravitt P, et al. Circumcision of HIV-infected men: effects on high-risk human papillomavirus infections in a randomized trial in Rakai, Uganda. J Infect Dis. 2010;201:1463-9.). However, it’s important to note that these data represent an exclusively adult cohort as there are no studies on the association between infant circumcision and risk for sexually transmitted disease. What can be justified based on this data is the counseling of the benefits of circumcision to an adult male to help reduce his risk of HPV related infection and disease, in addition to modifiable behaviors such as condom use.

Prevention of HPV infection and subsequent penile cancer risk can also be accomplished with vaccines. There are two prophylactic HPV vaccines have been developed that can play an important role in the prevention of HPV transmission. This includes the quadrivalent and 9-valent HPV vaccines (Gardasil and Gardasil 99. Svare EI, Kjaer SK, Worm AM, Osterlind A, Meijer CJ, Brule AJ van den. Risk factors for genital HPV DNA in men resemble those found in women: a study of male attendees at a Danish STD clinic. Sex Transm Infect. 2002;78:215-8.) that have been licensed for use in females and males (1717. Meites E, Kempe A, Markowitz LE. Use of a 2-Dose Schedule for Human Papillomavirus Vaccination - Updated Recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2016;65:1405-1408.). The efficacy of these vaccines has been demonstrated in recent studies among HPV-negative men and women (1818. Giuliano AR, Palefsky JM, Goldstone S, Moreira ED Jr, Penny ME, Aranda C, et al. Efficacy of quadrivalent HPV vaccine against HPV Infection and disease in males. N Engl J Med. 2011;364:401-11. Erratum in: N Engl J Med. 2011;364:1481., 1919. Villa LL, Costa RL, Petta CA, Andrade RP, Ault KA, Giuliano AR, et al. Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial. Lancet Oncol. 2005;6:271-8.). Vaccine administration is approved for males aged 9 through 26 years (1717. Meites E, Kempe A, Markowitz LE. Use of a 2-Dose Schedule for Human Papillomavirus Vaccination - Updated Recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2016;65:1405-1408.) and can be given prior to the counseling of undergoing circumcision later in life. Therefore, it may be reasonable to delay circumcision as a neonate until the patient approaches sexual maturity. This can prevent the need for routine circumcision for all male neonates and reserve circumcision to only those who develop risk factors such as high risk sexual practices or abnormalities such as phimosis or balanitis.

Penile carcinoma can be preventable through advocating daily hygiene and HPV prevention. Although circumcision can help reduce risk factors for penile cancer development, this does not necessarily warrant a requirement for circumcision as a neonate given the rarity of disease and alternative strategies in prevention. Through improved efforts in modifiable behaviors and implementation of HPV vaccination, this can curb penile cancer risk until the patient can make an informed decision regarding circumcision later in life.

REFERENCES

  • 1
    Sorokan ST, Finlay JC, Jefferies AL; Canadian Paediatric Society, Fetus and Newborn Committee, Infectious Diseases and Immunization Committee. Newborn male circumcision. Paediatr Child Health. 2015;20:311-20.
  • 2
    American Academy of Pediatrics Task Force on Circumcision. Circumcision policy statement. Pediatrics. 2012;130:585-6.
  • 3
    Larke NL, Thomas SL, Santos Silva I dos, Weiss HA. Male circumcision and penile cancer: a systematic review and meta-analysis. Cancer Causes Control. 2011;22:1097-110.
  • 4
    Barnholtz-Sloan JS, Maldonado JL, Pow-sang J, Giuliano AR. Incidence trends in primary malignant penile cancer. Urol Oncol. 2007;25:361-7. Erratum in: Urol Oncol. 2008;26:112.
  • 5
    Frisch M, Friis S, Kjaer SK, Melbye M. Falling incidence of penis cancer in na uncircumcised population (Denmark 1943-90). BMJ. 1995;311:1471.
  • 6
    Maiche AG. Epidemiological aspects of cancer of the penis in Finland. Eur J Cancer Prev. 1992;1:153-8.
  • 7
    Morris BJ, Gray RH, Castellsague X, Bosch FX, Halperin DT, Waskett JH, et al. The Strong Protective Effect of Circumcision against Cancer of the Penis. Adv Urol. 2011;2011:812368.
  • 8
    Baldur-Felskov B, Hannibal CG, Munk C, Kjaer SK. Increased incidence of penile cancer and high-grade penile intraepithelial neoplasia in Denmark 1978-2008: a nationwide population-based study. Cancer Causes Control. 2012;23:273-80.
  • 9
    Svare EI, Kjaer SK, Worm AM, Osterlind A, Meijer CJ, Brule AJ van den. Risk factors for genital HPV DNA in men resemble those found in women: a study of male attendees at a Danish STD clinic. Sex Transm Infect. 2002;78:215-8.
  • 10
    Kjaer SK, Munk C, Winther JF, Jørgensen HO, Meijer CJ, Brule AJ van den. Acquisition and persistence of human papillomavirus infection in younger men: a prospective follow-up study among Danish soldiers. Cancer Epidemiol Biomarkers Prev. 2005;14:1528-33..
  • 11
    Nielsen A, Munk C, Kjaer SK. Trends in incidence of anal cancer and high-grade anal intraepithelial neoplasia in Denmark, 1978-2008. Int J Cancer. 2012;130:1168-73.
  • 12
    Baandrup L, Varbo A, Munk C, Johansen C, Frisch M, Kjaer SK. In situ and invasive squamous cell carcinoma of the vulva in Denmark 1978-2007-a Nationwide population-based study. Gynecol Oncol. 2011;122:45-9.
  • 13
    Backes DM, Kurman RJ, Pimenta JM, Smith JS. Systematic review of human papillomavirus prevalence in invasive penile cancer. Cancer Causes Control. 2009;20:449-57.
  • 14
    Castellsagué X, Albero G, Clèries R, Bosch FX. HPV and circumcision: a biased, inaccurate and misleading meta-analysis. J Infect. 2007;55:91-3.
  • 15
    Tobian AA, Serwadda D, Quinn TC, Kigozi G, Gravitt PE, Laeyendecker O, et al. Male circumcision for the prevention of HSV-2 and HPV infections and syphilis. N Engl J Med. 2009;360:1298-309.
  • 16
    Serwadda D, Wawer MJ, Makumbi F, Kong X, Kigozi G, Gravitt P, et al. Circumcision of HIV-infected men: effects on high-risk human papillomavirus infections in a randomized trial in Rakai, Uganda. J Infect Dis. 2010;201:1463-9.
  • 17
    Meites E, Kempe A, Markowitz LE. Use of a 2-Dose Schedule for Human Papillomavirus Vaccination - Updated Recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2016;65:1405-1408.
  • 18
    Giuliano AR, Palefsky JM, Goldstone S, Moreira ED Jr, Penny ME, Aranda C, et al. Efficacy of quadrivalent HPV vaccine against HPV Infection and disease in males. N Engl J Med. 2011;364:401-11. Erratum in: N Engl J Med. 2011;364:1481.
  • 19
    Villa LL, Costa RL, Petta CA, Andrade RP, Ault KA, Giuliano AR, et al. Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial. Lancet Oncol. 2005;6:271-8.

Publication Dates

  • Publication in this collection
    Jan-Feb 2017
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