Safety and immunogenicity of a vaccine targeting human papillomavirus types 6, 11, 16 and 18: A randomized, double-blind, placebo-controlled trial in Chinese males and females

Abstract

In this randomized, double-blind, placebo-controlled trial, 9–15 year old Chinese males (n = 100) and 9–45 year old Chinese females (n = 500) from Wuzhou, Guangxi, China were randomized (1:1) to receive either quadrivalent HPV vaccine or adjuvant-containing placebo. Blood samples were obtained at day 1 and one month post-dose 3 to determine the level of vaccine-induced antibodies. Among vaccine recipients, high antibody levels were observed for each of the four HPV types and seroconversion was >96%. The vaccine was generally well tolerated, with no vaccine-related serious adverse events. This study demonstrated that the quadrivalent HPV vaccine is highly immunogenic and generally well tolerated among Chinese males and females.

Introduction

Human papillomavirus (HPV) is one of the most common sexually transmitted infections world-wide with over 50% of sexually active adults becoming infected during their lifetime [1]. The causal role of HPV in all cancers of the uterine cervix is firmly established [2], [3]. Most cancers of the vagina and anus are likewise caused by HPV [4], as are a proportion of cancers of the head and neck [5]. In addition, HPV infection can lead to genital warts and recurrent respiratory papillomatosis, both of which cause substantial morbidity and health care costs [6].

Every year, nearly 500,000 cases of cervical cancer are diagnosed worldwide [7]. In China, each year approximately 45,000 women are diagnosed with cervical cancer and 25,000 die from the disease [7]. Cervical cancer ranks as the 7th most frequent cancer among Chinese women and the 5th most frequent cancer among women between ages 15 and 44. Until recently, there were no established national programs for cervical cancer prevention in China [8], [9]. Since 2009, free cervical cancer screening examinations have been available for women between 35 and 59 years under a government sponsored program which concentrates on China's less developed central and western regions [9].

As seen in the United States and Europe, approximately 70% of cervical cancers in China are attributed to HPV16 and HPV18 [7]. A study conducted in 19 hospitals across seven regions of China showed that HPV16 and 18 were the most common types detected in squamous cell carcinoma, together accounting for 84.5% [10]. In a recent meta-analysis, the prevalence of HPV in genital warts in mainland China was estimated at 84.2%, with 83% attributed to HPV6/11 [11]. The data on HPV prevalence is available only in limited regions, and has ranged from 15% to 21% [12], [13].

There are currently two prophylactic HPV vaccines. A bivalent HPV 16/18 vaccine, and a quadrivalent HPV 6/11/16/18 vaccine. Both vaccines are highly efficacious and immunogenic in females [14], [15], [16]. The quadrivalent HPV vaccine has also been shown to be highly efficacious and immunogenic in males [17]. For the quadrivalent HPV vaccine, there was high prophylactic efficacy and antibody response among the Asia Pacific women who were enrolled across the phase 2/3 clinical trials, which included Hong Kong, New Zealand, the Philippines, Singapore, Taiwan, and Thailand [18]. However, the immunogenicity, safety and efficacy of the vaccine have not been studied in Chinese males and females. As China is the largest developing country and has witnessed a cervical cancer mortality increase of 4.1% per year among younger urban females (35–44 years), a clinical trial to assess the immunogenicity of the vaccine in China is warranted. In this randomized, placebo controlled trial, we assessed the safety and immunogenicity of the quadrivalent HPV vaccine in Chinese males and females.