No abstract

In cervical cancer, human papillomavirus type 18 (HPV 18) and HPV 16 are predominantly related to adenocarcinomas (ADCs) and squamous cell carcinomas (SCCs), respectively. Here, we studied whether the geographically distributed HPV intratypic variants are also associated with histologically different tumors. Infection with an oncogenic type of the human papillomavirus (HPV) is now established as the central cause of cervical cancer. 1 Almost 30 distinct types of HPV have been described infecting the genital tract. The oncogenic types HPV 16 and HPV 18 are the most prevalent in cervical cancer. The distribution of HPV types varies geographically, yet worldwide HPV 16 is present in 50% and HPV 18 in 14% of cervical cancers. 2 Indonesia is described as the only country where the number of HPV 16-positive cervical carcinomas is surpassed by the number of HPV 18-positive carcinomas, with a prevalence of 32% and 49%, respectively. 2 Generally, HPV 16 predominates in squamous cell carcinoma (SCC), whereas HPV 18 is predominant in adenocarcinomas and adenosquamous carcinomas (ADCs). 3 However, in previous studies, we found a difference in proportion of ADCs in HPV 18-positive tumors. 4,5 In Indonesia, the proportion of ADCs in HPV 18-positive tumors was larger as compared to Suriname and the Netherlands. We hypothesize that this difference is to be explained by the geographical distribution of intratypic variants, that, similar to HPV types, might be preferentially associated with ADCs or SCCs. 6 Two studies suggested an association between HPV intratypic variants and histopathology, but both included very small numbers of HPV 18-positive tumors. 7,8 HPV intratypic variants are defined as having less than 2% sequence variation compared to the prototype strain, whereas HPV types have more than 10% difference in nucleotide sequence and the infrequently observed subtypes differ by 2-10%. 9 The intratypic variants are divided into phylogenetic branches. HPV 18 has 3 variant branches, a European, an African and an Asian Amerindian branch. 10 HPV 16 is divided into 6 phylogenetic branches, 6 plus the Javanese branch that we recently found to be prevalent in a large number of Indonesian cervical carcinomas. 11 Some variants of HPV 16, the HPV type most investigated, have been associated with increased oncogenicity. 9 Little is known about the oncogenicity of HPV 18 variants. 12 In the present study, we assessed the distribution of intratypic HPV 18 and HPV 16 variants in ADCs and SCCs. Moreover, we did a sequence analysis on the E6 and E7 open reading frames (ORFs). We performed this study in patients from 3 different countries in order to investigate a wide range of ethnicities and variants. In the Indonesian group, a large majority of women are Javanese. 5 The Surinamese population consists of several ethnical groups, the most important being the Creoles, Hindustani, Javanese, bush Negro and Amerindians. 4 In the Netherlands, the majority of the population is Caucasian. We observed that HPV 18 intratypic variants are differe...