Antonio L. Cubilla

Knowledge about human papillomaviruses (HPV) types involved in anal cancers in some world regions is scanty. Here, we describe the HPV DNA prevalence and type distribution in a series of invasive anal cancers and anal intraepithelial neoplasias (AIN) grades 2/3 from 24 countries. We analyzed 43 AIN 2/3 cases and 496 anal cancers diagnosed from 1986 to 2011. After histopathological evaluation of formalin-fixed paraffin-embedded samples, HPV DNA detection and genotyping was performed using SPF-10/DEIA/LiPA25 system (version 1). A subset of 116 cancers was further tested for p16(INK4a) expression, a cellular surrogate marker for HPV-associated transformation. Prevalence ratios were estimated using multivariate Poisson regression with robust variance in the anal cancer data set. HPV DNA was detected in 88.3% of anal cancers (95% confidence interval [CI]: 85.1-91.0%) and in 95.3% of AIN 2/3 (95% CI: 84.2-99.4%). Among cancers, the highest prevalence was observed in warty-basaloid subtype of squamous cell carcinomas, in younger patients and in North American geographical region. There were no statistically significant differences in prevalence by gender. HPV16 was the most frequent HPV type detected in both cancers (80.7%) and AIN 2/3 lesions (75.4%). HPV18 was the second most common type in invasive cancers (3.6%). p16(INK4a) overexpression was found in 95% of HPV DNA-positive anal cancers. In view of the results of HPV DNA and high proportion of p16(INK4a) overexpression, infection by HPV is most likely to be a necessary cause for anal cancers in both men and women. The large contribution of HPV16 reinforces the potential impact of HPV vaccines in the prevention of these lesions.

In 227 cases of human pancreas cancer (100 pancreatectomy specimens and 127 autopsies), pancreas duct epithelium not involved by invasive cancer was examined. Pancreas duct epithelium from 100 autopsies of patients with nonpancreatic cancer, matched by age and sex to the pancreas cancer autopsy cases, was used for control studies. The prevalence of squamous metaplasia, pyloric gland metaplasia, mucous hypertrophy, and focal epithelial hyperplasia was not greatly different in the two groups. Ductal papillary hyperplasia was three times more prevalent in pancrease cancer than in controls. Marked atypia occurred in 20%, and carcinoma in situ, in 18% of the pancreas cancer cases, but neither change was seen in the control cases. It is possible that focal epithelial hyperplasia was a precursor change but that it was overgrown by the cancer. Papillary hyperplasia could not be properly evaluated as a precursor lesion because of duct obstruction, but practically all cases of marked atypia and carcinoma in situ occurred in papillary lesions. Marked atypia and carcinoma in situ, by analogy to other cancers, would appear to be precursor lesions, and their presence in association with invasive cancer lends hope to the possibility that there is a significant, recognizable, in situ phase of the disease before invasive cancer occurs.