Human Papillomavirus and Oral Cancer: the International Agency for Research on Cancer Multicenter Study

Background: Human papillomavirus (HPV), the causal agent of cervical cancer, appears to be involved in the etiology of cancer of the oral cavity and oropharynx. To investigate these associations, we conducted a multicenter case-control study of cancer of the oral cavity and oropharynx in nine countries. Methods: We recruited 1670 case patients (1415 with cancer of the oral cavity and 255 with cancer of the oropharynx) and 1732 control subjects and obtained an interview, oral exfoliated cells, and blood from all participants and fresh biopsy specimens from case patients. HPV DNA was detected by polymerase chain reaction (PCR). Antibodies against HPV16 L1, E6, and E7 proteins in plasma were detected with enzyme-linked immunosorbent assays. Multivariable models were used for case-control and case-case comparisons. Results: HPV DNA was detected in biopsy specimens of 3.9% (95% confidence interval [CI]=2.5% to 5.3%) of 766 cancers of the oral cavity with valid PCR results and 18.3% (95% CI=12.0% to 24.7%) of 142 cancers of the oropharynx (oropharynx and tonsil combined) with valid PCR results. HPV DNA in cancer biopsy specimens was detected less frequently among tobacco smokers and paan chewers and more frequently among subjects who reported more than one sexual partner or who practiced oral sex. HPV16 DNA was found in 94.7% of HPV DNA-positive case patients. HPV DNA in exfoliated cells was not associated with cancer risk or with HPV DNA detection in biopsy specimens. Antibodies against HPV16 L1 were associated with risk for cancers of the oral cavity (odds ratio [OR]=1.5, 95% CI=1.1 to 2.1) and the oropharynx (OR=3.5, 95% CI=2.1 to 5.9). Antibodies against HPV16 E6 or E7 were also associated with risk for cancers of the oral cavity (OR=2.9, 95% CI=1.7 to 4.8) and the oropharynx (OR=9.2, 95% CI=4.8 to 17.7). Conclusions: HPV appears to play an etiologic role in many cancers of the oropharynx and possibly a small subgroup of cancers of the oral cavity. The most common HPV type in genital cancers (HPV16) was also the most common in these tumors. The mechanism of transmission of HPV to the oral cavity warrants further investigation.

The Unexpected Preference for the fac-Isomer with the Tris(5-ester-substituted-2,2′-bipyridine) Complexes of Ruthenium(II)

The synthesis of a number of new 2,2'-bipyridine ligands, functionalized with bulky ester side groups is reported (L2 - L8). Their reaction with [Ru(DMSO)4Cl2] gives rise to tris-chelate ruthenium(II) metal complexes which show an unusually high proportion of the fac-isomer, as judged by 1H NMR following conversion to the ruthenium(II) complex of 2,2'-bipyridine-5-carboxylic acid methyl ester (L1). The initial reaction appears to have thermodynamic control with the steric bulk of the ligands causing the third ligand to be labile under the reaction conditions used, giving rise to disappointing yields and allowing rearrangement to the more stable facial form. DFT studies indicate that this does not appear to be as a consequence of a metal centered electronic effect. The two isomers of [Ru(L1)3](PF6)2 were separated into the two individual forms using silica preparative plate chromatographic procedures, and the photophysical characteristics of the two forms compared. The results appear to indicate that there is no significant difference in both their room temperature electronic absorption and emission spectra or their excited state lifetimes at 77K.

Enantiocomplementary preparation of (S)- and (R)-1-pyridylalkanols via ketone reduction and alkane hydroxylation using whole cells of Pseudomonas putida UV4

A previously unreported alcohol dehydrogenase enzyme in the mutant soil bacterium Pseudomonas putida UV4 catalyses the reduction of 2-, 3- and 4-acylpyridines to afford the corresponding (S)-1-pyridyl alkanols, with moderate to high e.e., whilst under the same conditions 2,6-diacetylpyridine is readily converted to the corresponding enantiopure C2-symmetric (S,S)-diol in one step. In contrast, the toluene dioxygenase enzyme in the same organism catalyses the hydroxylation of 2- and 3-alkylpyridines to (R)-1-(2-pyridyl) and (R)-1-(3-pyridyl)alkanols. This combination of oxidative and reductive biotransformations thus provides a method for preparing both enantiomers of chiral 1-pyridyl alkanols using one biocatalyst.