Cancer Update 2008

Department of Ophthalmology, Royal Gwent Hospital, Cardiff Road, Newport NP20 2UB, Wales, UK. david.hughes@gwent.wales.nhs.uk

The role of human papillomavirus (HPV)infection in eye cancer disease is controversial. However, a recent case illustrates the possible role of HPV in conjunctival squamous carcinoma and the potentially devastating effects of this disease. The development of two vaccines to prevent infection with HPV types most commonly cancer associated with anogenital cancers has led to debate about the pros and cons of a national immunisation programme to prevent cervical cancer. The introduction of such a vaccination programme may have an additional cancer beneficial effect on the occurrence of some head and neck, including ocular, cancers. This review discusses the nature of papillomaviruses, cancer mechanisms of infection and cancer carcinogenesis, the possible role of HPV in eye cancer disease, and finally the likely impact of the new prophylactic cancer vaccines.

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The New York Eye Cancer Center, 115 East 61st Street, New York, NY 10065, USA.

AIM: To evaluate 18-fluoro-2-deoxyglucose (FDG) whole-body positron emission tomography/computed radiographic tomography (PET/CT) for lymph node and metastatic staging of patients with conjunctival melanoma. METHODS: Fourteen patients with T3 (n = 13) and T4 (n = 1) conjunctival melanoma (as defined in Chapter 42 of the AJCC staging manual) were staged for metastatic disease with PET/CT imaging with fusion. The patients had lymph node and clinical staging evaluations before PET/CT imaging. PET/CT images were studied for the presence and distribution of metastatic conjunctival melanoma (determined by standardised uptake values) and later confirmed by biopsy. MRI imaging was performed if abnormalities were noted on PET/CT images. RESULTS: Fourteen patients with conjunctival melanoma underwent PET/CT imaging. Seven were newly diagnosed (presurgical screening), and seven had undergone prior treatment (follow-up group). Only one patient with conjunctival melanoma (7.1%) was found to have metastatic disease on PET/CT imaging. Abnormal foci were found in the liver, lung, peritoneal cavity, lumbar spine as well as a supraclavicular node (T4N1M4). All liver function tests were normal. The mean length of follow-up after PET/CT imaging was 13 months (range 4-30 months). CONCLUSIONS: PET/CT imaging did not reveal any regional or systemic metastasis among 14 patients with advanced, diffuse and multifocal disease.

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Department of Ophthalmology, Chungnam National University Hospital, #640 Daesa-dong, Jung-gu, Daejeon 301-721, Korea. kcs61@cnu.ac.kr

BACKGROUND/AIMS: Helicobacter pylori is well known to be responsible for gastric mucosa-associated lymphoid tissue (MALT) lymphoma. This study evaluates whether H pylori is also responsible for conjunctival MALT lymphoma and which strain of H pylori is associated with conjunctival MALT lymphoma. METHODS: Fifteen cases of conjunctival MALT lymphoma were investigated. Eight biopsies of normal conjunctiva were also investigated as controls. The specimens were investigated for the presence of H pylori DNA with polymerase chain reaction (PCR) using 16S rDNA primer. When the PCR using 16S rDNA was positive for H pylori, the specimens were analysed for the virulent gene with PCR using vacA s1/2 primer and vacA m1/2 primer. RESULTS: H pylori DNA was identified in all 15 specimens of conjunctival MALT lymphomas and none of the controls. Of these 15 H pylori positive lymphoma specimens, the vacA s1 and vacA m2 alleles were detected in two, and only vacA s1 allele was detected in 11. CONCLUSIONS: H pylori is thought to play a role in the pathogenesis of conjunctival MALT lymphoma, and H pylori with vacA s1 allele appears to be a virulent strain for conjunctival MALT lymphoma.

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Pathology Department, Regina Elena Cancer Institute, Rome, Italy.

Genital human papillomavirus (HPV) is the causative agent of cervical cancer and is the most common sexually transmitted infection. Only limited and controversial data are available regarding HPV transmission in male sexual partners of women with cervical intraepithelial neoplasia (CIN). The aim of this study was to investigate the prevalence and the genotype distribution of HPV in penile scrapings of a series of Italian men, who had no visible penile lesions and were partners of women who were affected, or had been affected previously by cervical intraepithelial neoplasia or who were infected with HPV. The concordance of the viral group in the infected partners was determined. A total of 77 penile scrapings were screened for HPV infection by the polymerase chain reaction, while 59 cervicovaginal brushings of their female partners were tested. 35% of evaluable male samples and 64% of female sexual partners were found to be HPV positive. In the 55 simultaneously evaluable couples, a concordance of 45% was found, 11 couples (20%) with both partners being HPV negative and 14 couples (25%) with both partners HPV positive (P = 0.001). Six out of the 14 couples (43%), where both partners were HPV positive, harbored the same HPV genotype group. These data, although preliminary, could support further the hypothesis that male HPV infection is more frequent in sexual partners of HPV positive or women with cervical intraepithelial neoplasia indicating that men could represent an important source of HPV transmission between sex partners. J. Med. Virol. 80: 1275-1281, 2008. (c) 2008 Wiley-Liss, Inc.

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Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), Hospital of the University of Mainz, Germany.

Classification of high-risk HPV types for cervical cancer screening depends on epidemiological studies defining HPV type-specific risk. The genotyping tests that are used, are however, not uniform with regard to type-specific detection rates making comparisons between different studies difficult. To overcome the lack of a “gold standard” four tests were evaluated crosswise using 824 cervical smears pretested by HC2. The tests evaluated were the L1-PCR-based assays PGMY09/11 LBA, HPV DNA Chip and SPF LiPA and an E1 consensus PCR followed by cycle sequencing (E1-PCR). A subset of 265 samples was tested in addition with the GP5+/6+ reverse line blot assay. Differences were noted in the sensitivity and range for specific HPV types, e.g. with detection rates for HPV53 ranging from 2.3% to 11.6%. HPV16 was the most prevalent type detected by all tests except for the SPF-10 LiPa, which detected HPV31 more often. Kappa values calculated ranged from poor (k = 0.20) to intermediate (k = 0.54) for HPV positivity, but were higher for high-risk type positivity (k = 0.31-0.61) and best for recognition of HPV16 (k = 0.53-0.72). The analytical sensitivity of the tests ranged between 15% and 97% for individual types and specificity was highly dependent on which test system was used as “gold standard” for the analysis. The results of histology were used for calculation of clinical sensitivity and specificity. E1-PCR, PGMY09/11 LBA and SPF-10 LiPA had a high clinical sensitivity (>95%) for the detection of cervical intraepithelial neoplasia 2 or higher, whereas the HPV DNA Chip reached only 84.1%. J. Med. Virol. 80: 1264-1274, 2008. (c) 2008 Wiley-Liss, Inc.

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Departments of Cancer Biology and.

Oncogene-mediated signaling to the host environment induces a subset of cytokines and chemokines. The Drosophila Dac gene promotes migration of the morphogenetic furrow during eye development. Expression of the cell-fate determination factor Dachshund (DACH1) was lost in poor prognosis invasive breast cancer. Mouse embryo fibroblasts derived from Dach1(-/-) mice demonstrated endogenous Dach1 constitutively represses cellular migration. DACH1 inhibited cellular migration and invasion of oncogene (Ras, Myc, ErbB2, c-Raf)-transformed human breast epithelial cells. An unbiased proteomic analysis identified and immunoneutralizing antibody and reconstitution experiments demonstrated IL-8 is a critical target of DACH1 mediating breast cancer cellular migration and metastasis in vivo. DACH1 bound the endogenous IL-8 promoter in ChIP assays and repressed the IL-8 promoter through the AP-1 and NF-kappaB binding sites. Collectively, our data identify a pathway by which an endogenous cell-fate determination factor blocks oncogene-dependent tumor metastasis via a key heterotypic mediator.

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Peking University, School and Hospital of Stomatology, Beijing 100081, China.

The aim of this study was to evaluate the anti-cancer effect of a novel organoselenium compound BBSKE (1,2-[bis(1,2-Benzisoselenazolone-3(2H)-ketone)]ethane, BBSKE, PCT: CN02/00412) on cell growth and apoptosis, focusing on the protein activity of Thioredoxin Reductase (TrxR) and Caspase-3, in oral squamous cell carcinoma (OSCC) in vitro and in vivo. Oral squamous cancer cell line Tca8113 was treated with various concentrations of BBSKE. Growth and apoptosis as well as the protein activities were analyzed. Morphologic changes of Tca8113 cells after 24h treatment of BBSKE were determined by fluorescence microscopy. The increase of Caspase-3 activity and decrease of Thioredoxin reductase (TrxR) activity were also measured. BBSKE induced a significant cell growth inhibition and elicited typical apoptotic morphologic changes (chromatic condensation, nucleus fragmentation). This phenomenon was accompanied by a change in protein activity of Thioredoxin reductase (TrxR) and Caspase-3. The anti-cancer effect of BBSKE was then studied in well-established Tca8113 xenografts in nude mice. In those tumors, anti-cancer effects were observed and significantly higher than the controls. Together, these results indicate that BBSKE can inhibit tongue cancer cell proliferation in vitro and in vivo, and induce apoptosis in Tca8113 cell lines partially via inhibiting the activity of TrxR and promoting the activity of Caspase-3.

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Department of Otolaryngology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.

BACKGROUND: Surgical margin is important to evaluate the adequacy of surgery related to tongue cancer. Despite the distances of margins, tumor components comprising the involved margins should also be investigated. Our aim was to explore the influences of tumor satellites on the clinical outcomes of involved margins. METHODS: Two hundred twenty-five patients with fresh tongue cancer were investigated. Nineteen patients with pathologically confirmed involved margins were enrolled. Based on the analysis of tumor components of involved margins, they were classified into 2 groups of either tumor-satellite involved margins (SMs) or main-tumor involved margins (MMs). RESULTS: The results showed that the clinical stages distribution was different: advanced stages in the MM group, and earlier in SM (p = .028). SM group had a higher incidence of neck recurrence (p = .040). Nonetheless, no difference in the disease-specific survival was noted. CONCLUSION: Tumor-satellite involved margins should be regarded as a worse prognosticator in tongue cancer. (c) 2008 Wiley Periodicals, Inc. Head Neck, 2008.

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Dept of Anesthesiology, The Stomatological Hospital of Chongqing Medical University, Chongqing 400015, China

OBJECTIVE: To compare the influence of propofol and isoflurane on pro-inflammatory and anti-inflammatory cytokine response to perioperative period of tongue cancer surgery. METHODS: Twenty-four adult patients undergone the operation of tongue cancer were assigned to two groups randomly, propofol group (Group P) and isoflurane group (Group I). In group P, anesthesia was induced with fentanyl 2-3 microg/kg, propofol 2 mg/kg, atracurium 0.6 mg/kg and maintained with propofol 5-8 mg x kg(-1) x h(-1) and inhalation of 50% nirous oxide (N2O:O2=50%:50%). In group I, anesthesia was induced with 3%-4% isoflurane, fentanyl 2-3 microg/kg, diazepam 0.06-0.1 mg/kg, atracurium 0.6 mg/kg and maintained with inhalation of 50% N2O and isoflurane (ended-tidal isoflurane was maintained at 0.6%), in two groups atracurium was given intermittently. Blood samples were taken from peripheral vein before anesthesia (TO), at the end of operation (T1), 24 h (T2) and 48 h (T3) after operation for determination of serum IL-6 and IL-10 concentrations. The mean arterial pressure (MAP) and body temperature in two groups were recorded. RESULTS: IL-6 and IL-10 levels increased significantly in two groups at T1, T2 and T3 compared with T0 (P < 0.01). The increasing trend of IL-6 and IL-10 levels were similar in both groups, whereas the level of IL-6 at T1 in propofol group was lower than that of isoflurane group significantly (P < 0.01), however the level of IL-10 was much higher in propofol group than that of isoflurane group at T1 and T2 (P < 0.05). CONCLUSION: The influence of total intravenous anesthesia of propofol on post-operation inflammatory response is much gentler than isoflurane.

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Osaka University Graduate School of Dentistry, Department of Oral and Maxillofacial Radiology.

Radiation therapy uses ionizing radiation to kill cancer cells and shrink tumors, with consideration to minimize harmful damages to health tissues. About 30% of all people with cancer are treated with radiation therapy, either alone or in combination with chemotherapy. Radiation therapy may be internal or external. In brachytheraphy as the internal radiation therapy the radioisotope is implanted into or near the tumor by tubes as the container. And it is often used for patients with the tongue cancer. External radiation, the type most often used, comes from a machine outside the body. It is usually used for shrinking tumors with bony invasions such as gingival cancer and improving the pain in patients with bony metastasis. For the primary bone tumor the radiation therapy is not always used because the radiosensitivity of the almost primary bone tumor is low.

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