Relationship Between Human Papillomavirus and Penile Cancer

Implications for Prevention and Treatment

Laura C. Kidd; Sharon Chaing; Juan Chipollini; Anna R. Giuliano; Philippe E. Spiess; Pranav Sharma

Disclosures

Transl Androl Urol. 2017;6(5):791-802. 

In This Article

Current Therapies Against HPV

Preventative Lifestyle Factors

Several factors predispose to genital HPV infection, yielding a series of preventative measures that can be undertaken to minimize this risk. Inconsistent or lack of condom use has been linked to higher rates of HPV infection.[65–69] Hence, their regular use is an important point on which to counsel patients. Alcohol[70] and tobacco use[71–73] also have a correlation with increased HPV infection independent of the number of sexual partners, so avoidance of these substances is advisable. A study of South African women showed high rates of co-infection with sexually-transmitted infections and HPV, most commonly herpes simplex type 2 and chlamydia trachomatis.[74] Likewise, higher number of sexual partners has been repeatedly demonstrated as a risk factor for genital HPV infection.[29,66,75–77] Another widely-investigated intervention for the reduction of HPV infection is circumcision.[16,78–83] In fact, a 2017 systematic review and meta-analysis of 24,401 men over 30 articles found significantly reduced odds of HPV prevalence in circumcised versus uncircumcised men [odds ratio (OR): 0.68; 95% CI: 0.56–0.82].[83] In summary, genital HPV infection risk can be reduced by circumcision and safe sex practices, including consistent condom use, reducing sexual partners and avoidance of sexually-transmitted infections, alcohol and tobacco.

HPV Vaccination

The first HPV vaccine (Gardasil, Merck & Co., Inc., Whitehouse Station, NJ, USA) was approved by the U.S. Food and Drug Administration (FDA) on June 8, 2006. It consisted of the quadrivalent strain, covering HPV types 6, 11, 16 and 18. This was later followed by the bivalent vaccine (Cervarix, GlaxoSmithKline Biologicals, Rixensart, Belgium) in 2009 for types 16 and 18.[84] Most recent to be FDA-approved in 2014 was the 9-valent version (Gardasil 9, Merck & Co., Inc.), protecting against HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58.[85]

The most robust available data regarding HPV vaccines regards cervical intraepithelial neoplasia and cervical cancer. A recent 10-year review and meta-analysis of several randomized controlled trials (RCT) cited efficacy from 89.8–100% at follow-up of 34.9 months to 9.4 years.[86] The most common adverse event was pain at the injection site and any serious adverse events were determined not to be vaccine-related.[86] Another 10-year review found similar efficacy, specifically of the bivalent and 9-valent vaccines, again, in CIN2+ lesions.[87]

However, regarding male HPV cases, a significant concern is the low rate of seroconversion after natural infection.[88] In addition, it has been suggested that HPV antibody seropositivity does not provide significant immunity to future infections like it does in women.[89] Fortunately, the quadrivalent HPV vaccine has been shown to be highly immunogenic in men age 16 to 26, with seroconversion by month 7, remaining elevated even at 36 months, with titers comparable to those in women.[90] A 2011 randomized, placebo-controlled double-blind trial of 4,065 boys age 16 to 26 across 18 countries showed promising efficacy of the quadrivalent vaccine in preventing external genital lesions. Observed efficacy in the intention-to-treat population was 60.2% (95% CI: 45.8–78.6); efficacy in the per-protocol group was 83.8% (95% CI: 61.2–94.4). PeIN was observed only in the placebo group. The trial showed similar adverse events data and time to seroconversion as previous reports.[91] Immunogenicity of the quadrivalent vaccine has also been demonstrated in a Phase II clinical trial in men aged 27–45 in the U.S. and Mexico, comparable to levels seen in younger men.[92]

Current recommendations from the Centers for Disease Control's Advisory Committee on Immunization Practices include routine HPV vaccination with either the bi- or quadrivalent vaccine in boys and girls age 11–12 years. Girls 13–26 who have not been previously vaccinated should receive the vaccine, as well as boys 13–21. Males up to age 26 who have sex with men or are immunocompromised should also be vaccinated. Vaccine schedule includes a single dose, followed by a second 1–2 months later and the final dose 6 months after that.[93] The 9-valent vaccine was added to the recommendations in 2015.[94] Dosing schedules were also recently updated in late 2016. If vaccinated before age 15, two doses of the HPV vaccine are appropriate, the second dose 6–12 months following the first. After 15 years of age, the standard 3-dose regimen still applies.[95]

Increasing evidence and awareness of the link between HPV and various cancers, and the availability of a vaccine, have made international vaccination programs more ubiquitous, including 18 countries.[96] In the United States specifically, the most recent data available show that in 2015, 28.1% of males received a full series of the HPV vaccine, compared to 41.9% of females and 34.9% of adolescents, overall.[97] The trend has been steadily improving with each year[98] but more work is needed to augment these numbers and work toward eradicating HPV. This certainly serves to emphasize the importance of appropriate patient counseling and advocacy for ongoing research.

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