Human papillomavirus serology and the risk of esophageal and gastric cancers: Results from a cohort in a high‐risk region in China

Abstract

Each year, esophageal and gastric cancers cause more than 900,000 deaths worldwide. Human papilloma virus (HPV), especially type 16, has been suggested to have a role in the etiology of esophageal cancer, however, the results of previous seroepidemiological studies have not been consistent. We conducted a large prospective study to examine the association between serum antibodies to HPV 16, HPV 18 and HPV 73 and subsequent development of esophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma (GCA), and gastric noncardia adenocarcinoma (GNCA) in a high-risk population for these cancers in Linxian, China. Case and control subjects for this study were selected from the 29,584 participants of the Linxian General Population Trial. Prediagnostic serum samples from 99 cases of ESCC, 100 cases of GCA, 70 cases of GNCA, and 381 age-and sex-matched controls were selected for this study. The presence of antibodies to HPV virus-like particles was determined by type-specific enzyme-linked immunosorbent assays. Fewer than 15% of ESCC, GCA, or GNCA cases were positive for each HPV type, and no significant associations were found. The adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for HPV 16 seropositivity and ESCC, GCA, and GNCA risk were 1.6 (0.8-3.3), 1.3 (0.6-2.8) and 0.4 (0.1-1.6), respectively. The comparable ORs (95% CIs) for HPV 18 were 1.0 (0.4-2.2), 0.9 (0.4-2.1) and 1.5 (0.6-3.4). For HPV 73, these figures were 1.3 (0.6-2.5), 1.2 (0.6-2.3) and 0.9 (0.4-2.1). The results of this study do not support a major role for HPV 16, HPV 18 and HPV 73 in the etiology of esophageal and gastric cancers in Linxian, China. ' 2006 Wiley-Liss, Inc.Key words: esophageal cancer; human papillomavirus; serology Oncogenic types of human papillomavirus (HPV), most notably HPV 16 and HPV 18, are recognized as the most significant risk factors for cervical cancer. 1 The role of HPV in the etiology of cancers of vulva, anus, penis and oropharyngeal cavity has also been established. 2 The role of HPV in the etiology of esophageal cancer, however, remains controversial. Syrjanen first suggested a role for HPV in the etiology of esophageal squamous cell carcinoma (ESCC) in 1982, based on observing characteristic histological findings suggesting the presence of HPV in benign esophageal epithelia and malignant esophageal tumors. 3 During the past 20 years, several studies have used a variety of techniques, including detection of HPV DNA in esophageal tumor tissues and serologic methods, to examine the association between exposure to HPV and risk of ESCC. 4 The results of HPV DNA studies have not been consistent: case series using polymerase chain reaction (PCR) have found evidence for the presence of HPV in the tumor tissues varying from 0 to 67%. 4 Type-restricted serologic assays for different HPV types using virus-like particles were first developed in the mid-1990s, 5 and were subsequently shown to be relatively specific for each HPV type. 6 Seroreactivity to HPV 16 is a strong marker of continuous past exp...

Human papillomavirus in high- and low-risk areas of oesophageal squamous cell carcinoma in China

“…A serological study in Linxian, China, where the ESCC risk is extremely high (Kamangar et al, 2006), found no significant association between seropositivity of HPV 16 and ESCC risk, although serum antibodies against HPV antigens are considered good markers of exposure to HPV in the past. Their results can be explained by the decrease or loss of antibodies against HPV capsid antigens during several decades after HPV infection until study subjects were examined and their blood samples were drawn (Lagergren et al, 1999).…”

“…In this study, the infection of oesophageal cells with high-risk HPV genotypes occurs in 13% of asymptomatic adults with no evidence of squamous dysplasia and a similar proportion of individuals with mild, moderate or severe dysplasia, suggesting that HPV infection is not a major risk factor for ESCC in this high-risk Chinese population (Gao et al, 2006). On top of that, an ESCC case -control study nested in a cohort in Linxian, China, could not find any evident case -control differences in the levels of serum antibody against HPV 16, 18 or 73 (Kamangar et al, 2006). Although the studies in Linxian could not confirm the relationship between HPV and ESCC, the fact does not necessarily deny the presence of such a relationship in other areas as the risk factor of ESCC is known to be heterogeneous.…”

High-Risk Human Papillomavirus in Esophageal Squamous Cell Carcinoma

“…Several explanations are possible; for example, serologic studies do not distinguish co-incidental HPV infection at other body sites from infection in the esophageal squamous epithelium. Moreover, there has been a lack of consistency in the serologic methods used to investigate the association, which might account for the divergent findings of studies (22)(23)(24)(25). To date, no firm evidence for a role for HPV in esophageal carcinogenesis has been established.…”

Human Papillomavirus and Carcinogenesis in the Upper Aero-Digestive Tract

“…European prospective serologic studies that used stored serum specimens [41] as well as a Chinese case-control study [42] found a strong association between the risk of ESCCs and seropositivity to HPV-16. In contrast, other retrospective studies conducted in Europe [43] and a large prospective serologic study in China [44] found no significant association of HPV-16 or HPV-18 with SCCs or adenocarcinomas of the esophagus.…”