Favorable clinical outcome of cervical cancers infected with human papilloma virus type 58 and related types

Abstract

To determine whether the status of human-papillomavirus (HPV) infection affects the clinical outcome of cervical carcinoma (CC), HPV genotype was prospectively determined in 94 consecutive CC cases subsequently followed for a median duration of 37.5 months. With a consensus PCR-RFLP method of HPV genotyping, 81 (86.2%) cancers were positive for HPV DNA. They were classified, according to the phylogenic similarities, into HPV-16-related (type 16, n ‫؍‬ 45; type 31, n ‫؍‬ 2), HPV-58-related (type 58, n ‫؍‬ 17; type 33, n ‫؍‬ 3; type 52, n ‫؍‬ 2) and HPV-18-related (type 18, n ‫؍‬ 8; type 68, n ‫؍‬ 1) groups, and analyzed in relation to clinical outcome. The following results were observed: (i) Type-58-related HPVs were more prevalent in the old age (older than the median age of 52) group than in the young age group (41% vs. 14.6%, p ‫؍‬ 0.045); (ii) 63% (5/8) of patients with advanced stages (III and IV) were HPV-negative, a figure much higher than that Cervical carcinoma (CC) is one of the most common malignancies both in incidence and in mortality in women worldwide. Epidemiologic and laboratory studies have revealed a multifactorial and multi-step process, with infection of oncogenic types of human papillomavirus (HPV) standing for the predominant role (zur Hausen, 1991; Muñoz et al., 1992). The integration of HPV DNA into host genome and over-expression of the E6 and E7 oncogenes appear to be critical steps in cancer development (Phelps et al., 1988). Consequently, HPV DNA is present in most high-grade squamous intra-epithelial lesions (HSIL) and invasive cancers of the uterine cervix (Muñoz et al., 1992).On the basis of differences in DNA sequences, more than 70 types of HPV have been identified, and about 20 of them are associated with CC. They were grouped, according to their prevalence in SIL and CC, into intermediate-risk types (31, 33, 35, 51, 52 and 58) and high-risk types (16, 18, 45 and 56) (Lorincz et al., 1992). But the biologic behavior and clinical relevance of this classification have not been confirmed. However, several reports have noted that HPV genotypes associated with lesions of similar pathologies are phylogenetically related (De Villiers, 1989;Chan et al., 1992;Bernard et al., 1994), and indicated amino-acid-sequencedependent oncogenic behavior of HPV. Accordingly, a phylogenetic study has related, by order of phylogenic branching, HPV types 58/33/67/52, types 16/31/35 and, in remote branches, types 56/51 and 18/68/45 (Bernard et al., 1994).A number of studies of the influence of HPV status on the clinical features of cervical cancers have produced conflicting results. HPV 16 was found to be more prevalent in welldifferentiated carcinomas (Riou et al., 1990), while HPV 18 was associated with adenocarcinoma (AC) and adenosquamous carcinoma (ASC) (Higgins et al., 1991;Chen et al., 1994) and younger age (Higgins et al., 1991;Lorincz et al., 1992;Nakagawa et al., 1996). In addition, HPV-18-positive CCs were found to have a poor prognosis (Rose et al., 1991;Nakagawa et al., 1996;Lombard et al...

Impact of multiple HPV infection on response to treatment and survival in patients receiving radical radiotherapy for cervical cancer

“…[5][6][7][8] A recent study found improved survival in patients with HPV 58 positive tumors. 33 The impact of multiple HPV infection, however, was not investigated. The incidence of multiple HPV infection varies and is related to the method of HPV detection.…”

“…32 Biotin-labeled, type specific double-stranded DNA probes for general screening (HPV 6,11,16,18,30,31,33,45, 51, 52) and type-specific probes against HPV 16, 18, 31 and 33 were used. This signal-amplified ISH method is considered to be highly specific and very sensitive for detection of HPV-DNA in tissue sections.…”

“…32 According to the manufacturer's information, the biotinylated type-specific ISH probes were selected for minimal cross-hybridization with other HPV-types. Using non-radioactive Southern blot hybridization at high stringency against 100 ng of cloned HPV DNA from types 6,11,16,18,30,31,33,35,45, 51 and 52 these probes were specific for HPV 16, 18, 31 and 33, respectively, without cross-reaction with the other HPV-types. These probes did also not react with normal human nuclear DNA when probed by ISH, or with E. coli DNA when tested by dot blot hybridization.…”

“…1 A strong causal relationship between infection with the human papillomavirus (HPV) and cervical cancer has been established. 2,3 More than 80 HPV types have been isolated so far but only the oncogenic HPV types 16,18,31,33,35,45, 51, 52, 58 and 59 are associated with a greater risk of cervical cancer. 4 Studies analyzing the relationship between HPV type and prognosis in patients with cervical cancer reported a worse outcome in patients with HPV-18-related tumors.…”

High-risk Human Papillomavirus Genotype Detection by Electrochemical DNA Chip Method

“…The remainder is due to other HPV types depending on geographical variations and ethnicity of the population (Smith et al, 2007). For example in Asian populations, HPV genotypes 52 and 58 are usually found while they are rare in Western countries (Lai et al, 1999). HPV typing provides important data for the distinction between high and low risk.…”