Original Research
Impact of the Quadrivalent HPV Vaccine on Disease Recurrence in Men Exposed to HPV Infection: A Randomized Study

https://doi.org/10.1111/jsm.12670Get rights and content

Abstract

Introduction

Human papillomavirus (HPV) is one of the most common sexually transmitted infections and is the cause of several different diseases in men and women. Although little is known about HPV infection in men, they are also in the risk group of HPV infection and play an important role in transmitting the virus to women.

Aim

To define the efficacy of the HPV vaccine through cross-immunization and its role in clearance of HPV infection, and to assess infection-associated factors in men.

Methods

This prospective randomized clinical study enrolled 171 evaluable men with genital warts between June 2009 and October 2013. After the initial treatment intervention, 91 patients were randomly assigned to receive HPV vaccine in three doses. Eighty patients were in the control (unvaccinated) group. One hundred-eleven men were single and 60 men were married. Patients who had previous treatment for pre-existing warts and medical disorders that needed chronic treatment or immunosuppression were not included in the randomization. Also 29 men with follow-up less than 12 months and incomplete vaccination were not included.

Main Outcome Measures

The patients were assessed regarding age, condom use, marital status, number of visible genital warts, and smoking status. Post-treatment follow-up was monthly up to 12th month.

Results

Mean age was 34 ± 7.6. One hundred fifteen patients were smokers. For the recurrence of warts, age, smoking, vaccination status were insignificant and marital status was significant in the univariable analysis; only marital status preserved significance (HR: 2.0 CI:1.29–3.12 P = 0.002) in the multivariable analysis including vaccination status, marital status, and smoking.

Conclusion

Among the investigated factors vaccination status was not but marital status significantly influenced wart recurrence. Married men had more recurrences in our population. Larger multicenter randomized clinical trials are lacking and seriously required to investigate the therapeutic effect of current quadrivalent HPV vaccine in genital warts. Coskuner ER, Ozkan TA, Karakose A, Dillioglugil O, and Cevik I. Impact of the quadrivalent HPV vaccine on disease recurrence in men exposed to HPV infection: A randomized study. J Sex Med 2014;11:2785–2791.

Introduction

Human papillomavirus (HPV) is one of the most common sexually transmitted infections and is the cause of several different diseases in men and women 1, 2. Although cancers of the cervix, vagina, vulva, penis, oral cavity, head and neck, and anal canal are attributable to HPV infection, anogenital warts are the most common outcome of it [3]. There are 148 recognized HPV types and among them high-risk subtypes HPV 16 and 18 account for 70% of cervical cancers in females, and low-risk subtypes HPV 6 and 11 account for 90% of genital warts found in male and females 4, 5. Jemal et al. reported that HPV-associated cancers accounted for 3.3% of all cancers in women and 2% of the total cancers in men in 2009 [6]. Men also play an important role in transmitting the virus to women. Improved understanding of the HPV infection course in men has an essential role to solve the problems related with the disease. Genital HPV infection is a sexually transmitted disease and it is predictable that male immunization may help prevent HPV transmission and this will reduce the load of HPV infection and HPV related diseases in women. Although the health authorities of most Western European countries introduced HPV vaccination especially for adolescent girls, immunization rates are not very impressive compared with other childhood vaccinations. The low immunization rates in women shows the importance of extending vaccination to males in order to achieve the greatest possible protection from cervical cancer [7].

Currently available HPV vaccines target the late protein 1 (L1) in the protein shell of DNA molecules of the virus, which is necessary for viral replication and assembly of newly formed virus particle in infected cells [8]. The U.S. Food and Drug Administration (FDA) approved a quadrivalent HPV vaccine against types 6, 11, 16 and 18 for females in aged 9–26 years in 2006 [9]. The HPV vaccine has also been shown to be preventive and safe in men. The vaccine is 85.6% effective at preventing persistent infection with HPV types 6, 11, 16, and 18 in men who are vaccinated before HPV exposure with these types and 90.4% effective at preventing anogenital lesions related to these types [10]. As a result, in 2009, FDA recommended the quadrivalent HPV vaccine for the prevention of external genital lesions caused by HPV 6, 11, 16, or 18 in males aged 9–26 years [11]. In 2010, the FDA included prevention of anal cancer in men and women as an additional indication for use of the quadrivalent HPV vaccine. HPV vaccines are most effective when given before exposure to HPV through sexual contact; however, individuals who may have already been exposed to HPV should still be vaccinated [12]. It has been shown that HPV vaccination is likely to induce neutralizing antibodies across HPV species [13].

The high prevalence of HPV infection and its serious medical, psychosexual, and relationship consequences make the prevention of HPV infection important for the field of sexual medicine [14]. Unfortunately current vaccination research has largely focused on females. After recent approval of quadrivalent HPV vaccine for males, the implementation of gender-based vaccination provides more argument. But there is still no randomized study about HPV vaccine for males known to have been exposed to HPV virus.

Section snippets

Aim

Our purpose in this randomized study was to define the importance of immunization and its role in clearance of HPV infection and to assess infection-associated factors in men. We tried to answer the question whether quadrivalent HPV vaccination can prevent HPV recurrence in men already exposed to this virus.

Methods

This prospective randomized clinical study enrolled 200 men with new onset genital warts living in the same area for at least 1 year, between June 2009 and October 2013. Genital warts were visibly diagnosed with magnifying glass after aceto-white test application whenever deemed necessary. Pathologic examination was performed in suspicious cases. Initial treatment is local excision with electrocautery (in larger pedunculated lesions) or electrocautery alone (in flat broad based lesions) with

Main Outcome Measures

The present study asseses the efficacy of HPV vaccination on previously HPV infected men. HPV infected men were randomly assigned to HPV vaccinated or control groups. The primary outcome measure was recurrence in both vaccinated and control groups. Secondary outcome measures included evaluation of the influence of modifying co-factors; marital status, smoking, condom use and the number of lesions.

Results

Mean age was 34.05 ± 7.61. All men were circumcised and heterosexual. Of those, 111 (65%) men were single and 60 (35%) were married. Among them, only 56 (32.7%) were nonsmokers; 115 (67.3%) were smokers (Table 1). Genital warts were determined predominantly in coronal sulcus, shaft of penis, pubic and perianal area. Number of cauterization sessions changed between 1 to 15 in four years in all men in both groups. Development of recurrence had been associated with increased number of genital warts

Discussion

HPV has been linked to various benign and malignant lesions occurring in mucosal and skin epithelia. Most HPV infections are transient and asymptomatic. Men have higher likelihood of HPV cure rate than women. Almost 75% of HPV infection in men cleared within 1 year [15]. But persistent infection with high-risk types can progress to a precancerous lesion and eventually to cancer. HPV 16 and 18 account for 70% of cervical cancers in females, and low- risk subtypes HPV 6 and 11 account for 90% of

Conclusion

Among the investigated factors vaccination status was not but marital status significantly influenced wart recurrence. Married men had more reccurrences in our population. Larger multi-center randomized clinical trials are lacking and seriously required to demonstrate the therapeutic effect of current quadrivalent HPV vaccine in genital warts.

Category 1

  • (a)

    Conception and Design

    Erik Rauf Coskuner; Tayyar Alp Ozkan; Ayhan Karakose; Ozdal Dillioglugil; Ibrahim Cevik

  • (b)

    Acquisition of Data

    Erik Rauf Coskuner; Tayyar Alp Ozkan; Ayhan Karakose; Ibrahim Cevik

  • (c)

    Analysis and Interpretation of Data

    Erik Rauf Coskuner; Tayyar Alp Ozkan; Ozdal Dillioglugil; Ibrahim Cevik

Category 2

  • (a)

    Drafting the Article

    Erik Rauf Coskuner; Tayyar Alp Ozkan; Ibrahim Cevik

  • (b)

    Revising It for Intellectual Content

    Erik Rauf Coskuner; Tayyar Alp Ozkan; Ayhan Karakose; Ozdal Dillioglugil; Ibrahim Cevik

Category 3

  • (a)

    Final

Acknowledgments

To the staff of our department, Miray Bayraktaroglu, for her kind efforts and help, for which we are most grateful.

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    Conflict of Interest: The authors report no conflicts of interest.

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