There is a high prevalence of human papillomavirus infection in American Indian women of the Northern Plains

Abstract

Objectives

Cervical cancer is the leading gynecological malignancy worldwide, and the incidence of this disease is very high in American Indian women. Infection with the human papillomavirus (HPV) is responsible for more than 95% of cervical squamous carcinomas. Therefore, the main objective of this study was to analyze oncogenic HPV infections in American Indian women residing in the Northern Plains.

Methods

Cervical samples were collected from 287 women attending a Northern Plains American Indian reservation outpatient clinic. DNA was extracted from the cervical samples and HPV-specific DNA was amplified by polymerase chain reaction (PCR) using the L1 consensus primer sets. The PCR products were hybridized with the Roche HPV Line Blot assay for HPV genotyping to detect 27 different low- and high-risk HPV genotypes. The Chi-squared test was performed for statistical analysis of the HPV infection and cytology diagnosis data.

Results

Of the total 287 patients, 61 women (21.25%) tested positive for HPV infection. Among all HPV-positive women, 41 (67.2%) were infected with high-risk HPV types. Of the HPV infected women, 41% presented with multiple HPV genotypes. Additionally, of the women infected with oncogenic HPV types, 20 (48.7%) were infected with HPV16 and 18 and the remaining 21 (51.3%) were infected with other oncogenic types (i.e., HPV59, 39, 73). Women infected with oncogenic HPV types had significantly higher (p = 0.001) abnormal Papanicolaou smear tests (Pap test) compared to women who were either HPV negative or positive for non-oncogenic HPV types. The incidence of HPV infection was inversely correlated (p < 0.05) with the age of the patients, but there was no correlation (p = 0.33) with seasonal variation.

Conclusions

In this study, we observed a high prevalence of HPV infection in American Indian women residing on Northern Plains Reservations. In addition, a significant proportion of the oncogenic HPV infections were other than HPV16 and 18.

Introduction

Statistical analyses released from the World Health Organization (WHO) suggest that cervical cancer is the second most common cancer in women worldwide [1], [2], [3]. It is estimated that each year approximately 493,000 new cases are diagnosed and 274,000 women die from cervical cancer worldwide [4]. The American Cancer Society estimates that in 2006, there will be 10,370 new diagnosed cases of cervical carcinoma and 3710 deaths associated with cervical cancer in the United States alone [5]. The incidence of cervical carcinoma is substantially higher among women of low socioeconomic status. Although Pap smear screening has decreased the incidence of cervical cancer in the United States, there are still pockets of the population, such as the American Indian women of the Northern Plains, that have a significantly higher rate of cervical cancer [6], [7].

In the Northern Plains, the American Indian population is comprised of Lakota, Mandan, Omaha, and Chippewa tribes that reside in North Dakota, South Dakota, Minnesota, Nebraska, and Iowa. This population suffers from significant medical problems including cancer, diabetes, high infant mortality, alcoholism, and other chronic illnesses [8], [9]. Smoking rates and the incidence of sexually transmitted infections are some of the highest in the country [9]. In addition, the women of this population suffer from high incidence of cervical carcinoma, which is a leading cause of cancer mortality in American Indian women [9]. There are marked regional differences in cervical cancer mortality rates among American Indian women in the United States. The Indian Health Service (IHS) of the Aberdeen area has calculated a female age-adjusted cervical cancer mortality rate of 15.6 per 100,000 people, which is 5 times that of the U.S. rate of 3.0 per 100,000 people [10]. While it is unclear why the cervical cancer mortality rate is so high in this area, the known risk factors for cervical carcinoma include multiparity, smoking, immunosuppression, poor nutrition, and human papillomavirus (HPV) infection [11]. However, the most important risk factors for cervical cancer are the persistence of an oncogenic HPV infection and a lack of timely screening [12], [13], [14].

The presence of HPV DNA in cervical tissues has implicated HPV as a causative agent in genital condylomatas, in lower female genital tract intraepithelial neoplasias, such as cervical intraepithelial neoplasia (CIN), and in invasive cervical carcinomas [15]. It has been demonstrated that HPV DNA can be detected in approximately 99% of all invasive cervical cancers [16]. In addition, HPV DNA is almost always present in condylomatas and high-grade dysplasias, such as CIN III [17]. HPV types 6 and 11 are known to induce exophytic condylomatas affecting the anogenital mucosa and lower vagina [18]. A subset of HPV types (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) are regarded as oncogenic, or high-risk, HPV viral types. This subset represents the predominant HPV genotypes detected in high-grade intraepithelial lesions (CIN II and III) and in carcinomas of the lower female genital tract [16], [17], [19].

A basic understanding of the HPV epidemiology is required in order to understand the role of various HPV types in the development of cervical cancer and to design effective vaccine strategies against the virus. Different populations may harbor varying HPV genotypes in the genital tract [16]. Thus far, the Northern Plains American Indian population has not been studied regarding their prevalence of HPV genotypes. Before utilizing HPV vaccines for a particular population, it is imperative to have relevant HPV genotyping data in order to provide an optimal vaccine for providing the best possible care for that population. This study provides the baseline data that will be accessible to insure that this population can be appropriately included in vaccine trials in the future.