p53 mutations in relation to human papillomavirus type 16 infection in squamous cell carcinomas of the head and neck

Abstract

The relationship between human papillomavirus (HPV) type 16 infection and p53 gene mutations was investigated in squamous cell carcinomas of the head and neck (SCCHN). HPV was detected by general primer-mediated and typespecific PCR. Alterations in the p53 gene were investigated using single-strand conformation polymorphism and sequence analysis in 27 SCCHN, of which 12 were HPV 16-positive and 15 were HPV-negative. Mutations The p53 tumour-suppressor gene (TSG) plays an important role in cellular responses to DNA damage, and alteration in the function of this gene is an important factor in the development of many types of cancer (Greenblatt et al., 1994). Mutations of the p53 TSG are common in squamous cell carcinomas of the head and neck (SCCHN) and can be detected early in the pathogenesis of these tumours (Brachman et al., 1992;Boyle et al., 1993;Greenblatt et al., 1994;Brennan et al., 1995). Inactivation of p53 function, however, also may occur as a result of interactions with certain viral proteins. In particular, the E6 protein of certain high-risk human papillomaviruses (HPVs) can bind to the p53 protein, promote its degradation and disrupt p53-mediated responses to DNA damage (Scheffner et al., 1990;Kessis et al., 1993). These findings raised the possibility that the presence of high-risk HPV types might obviate a requirement for p53 gene alterations, and initial studies of cervical carcinoma did indeed support an inverse correlation between the presence of HPV and p53 mutations . Further studies, however, have suggested that this apparently negative association may reflect an overall low prevalence of p53 mutations in tumours from this site, irrespective of HPV infection (Fujita et al., 1992;Helland et al., 1993).SCCHN provide an alternative group of tumours for investigating the relationship between HPV and p53 gene alterations as over 40% of these carcinomas have been reported to contain p53 mutations (Brachman et al., 1992;Boyle et al., 1993) and high-risk HPV types, predominantly HPV 16, have been detected in over 20% of tumours (Snijders et al., 1996). The relationship between HPV infection and p53 gene alterations in head and neck cancer is uncertain. The majority of studies of SCCHN have used p53 immunodetection rather than mutational analysis (Gorgoulis et al., 1994;Salam et al., 1995) or have concentrated largely on cell lines (Brachman et al., 1992;Min et al., 1994;Yeudall et al., 1995). Brachman et al. (1992) and Min et al. (1994) did not detect HPV 16 or 18 and p53 mutations simultaneously, though the number of HPV-positive samples in each study was very small, comprising only 3 and 2 samples, respectively. In contrast, Yeudall et al. (1995) detected HPV 16 in 2 of 8 oral carcinoma cell lines containing p53 mutations, though in both cases HPV 16 was undetectable in cells in later passages. Results from a study by Snijders et al. (1994a), however, indicate that high-risk HPV types and p53 mutations co-exist in a small number of tonsillar carcinomas; p53 mutations were detected in 2/11 HPV-...

“High Risk” HPV Types Are Frequently Detected in Potentially Malignant and Malignant Oral Lesions, But Not in Normal Oral Mucosa

“…As expected by the high prevalence of HPV in our patient group, no correlation was established between viral presence and other clinicopathologic characteristics (age, gender, and cancer differentiation). Such associations have been reported by some groups (13,15,38) but could not be confirmed by others (34,43,59). In addition, anatomic site seems to be an important factor that determines the susceptibility of squamous epithelium to HPV transformation, with the tonsillar region being more sensitive (13,15,22,35).…”

“…In patients who had proliferative disorders, HPV positivity exceeded the percentage of smoking (71.7%), which is considered a major risk factor for oral carcinogenesis (3). Most studies agree that there is no statistically significant correlation between HPV prevalence and smoking history, although it seems that both tobacco and HPV infection may participate in the tumorigenic process in oral mucosa (13,29,34,38,43).…”

Papillary squamous cell carcinomas of the upper aerodigestive tract: A clinicopathologic and molecular study

“…Thirty-eight cases were identified and retrospectively reviewed for clinicopathologic features, including patient demographics, sites of tumor origin, and extent of disease, and treatment modalities were extracted from these records. Of these, tissue blocks for molecular analysis were available for 14 cases, and follow-up data for at least 5 years after diagnosis (mean, 3 years) were available for 25 For polymerase chain reaction (PCR), oligonucleotide primers to amplify glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and HPV gene sequences were synthesized commercially (Genosys, The Woodlands, TX). Consensus primers were used to amplify an approximately 450-bp PCR product from an L1 open reading frame of HPVs 6,11,16,18,33.…”

Involvement of intact HPV16 E6/E7 gene expression in head and neck cancers with unaltered p53 status and perturbed pRb cell cycle control

“…Evidence has accumulated that some of the oncogenic HPV types are associated with a subset of head and neck cancers, since HPV DNA was found to be present in HNSCC with various morphology and from various sites (oropharynx, oral cavity, larynx, hypopharynx, nasopharynx), with HPV16 DNA strongly predominating over HPV18, 33, and further types (de Villiers et al, 1985;Maitland et al, 1987;Yeudall and Campo, 1991;Rassekh et al, 1998;for review, zur Hausen, 1996). In further studies, a rather frequent coexistence of HPV DNA and p53 mutations was found, and again all sites and histological grades were involved (Barten et al, 1995;Chiba et al, 1996;Scholes et al, 1997;He et al, 1997). This is in strong contrast to the situation in cervical and other anogenital cancers which show an almost complete inverse correlation between HPV and p53 mutations and which share a conspicious undierentiated (basaloid) morpholgy (Schener et al, 1991;Fujita et al, 1992;Crook et al, 1992;Milde-Langosch et al, 1995;zur Hausen, 1996).…”