Risk factors for invasive squamous cell carcinoma of the vulva and vagina--population-based case-control study in Denmark.

The etiology of vulvar and vaginal squamous cell carcinoma (VV-SCC) has received little attention. A total of 182 women with invasive VV-SCC (116 with VV-SCC(vulva), 66 with VV-SCC(vagina)), 164 uterine corpus cancer controls and 518 population controls were interviewed in a population-based case-control study in Denmark, and 87 (48%) of the VV-SCC cases had tissue samples examined for human papillomavirus (HPV) DNA using the GP5+/6+ PCR-EIA assay and subsequent reverse line blotting for HPV typing. Logistic regression-derived odds ratios with 95% confidence intervals served as relative risks. Cervical cancer-associated high-risk HPVs (hrHPVs) were detectable in most (89%) examined cases of VV-SCC(vagina) and in half (50%) of cases of VV-SCC(vulva) (p < 0.001). In site-specific multivariate logistic regression analyses, statistically significant risk factors for both VV-SCC(vulva) and VV-SCC(vagina) included measures of hrHPV exposure (anogenital warts for VV-SCC(vulva); cervical neoplasia and poor genital hygiene for VV-SCC(vagina)), tobacco smoking and alcohol consumption. Furthermore, socioeconomic variables (marital status and years at school) were associated with risk of VV-SCC(vulva). Comparing hrHPV-positive and hrHPV-negative VV-SCCs in polytomous logistic regression analysis revealed that tobacco smoking and cervical neoplasia were significant risk factors only for hrHPV-positive VV-SCCs. Our study shows that VV-SCC(vulva) and VV-SCC(vagina) share measures of prior hrHPV exposure, tobacco smoking and alcohol consumption as statistically significant risk factors. HPV vaccination programs aimed at reducing the burden of cervical cancers are likely to also provide considerable protection against VV-SCCs.

Metastasizing malignant pleomorphic adenoma in a young man.

We present the case of a younger man with metastasizing carcinoma of unknown primary site, where autopsy revealed a malignant pleomorphic adenoma (MPA) of the submandibular gland. MPA is very rare in young persons.

Temporal morphogenesis of herpes simplex virus type 1-infected and brefeldin A-treated human fibroblasts.

BACKGROUND: Insights in the herpesvirus-cell interactions are of general cell biology interest, especially to studies of intracellular transport, and of considerable significance in the efforts to generate drugs, vaccines, and gene therapy. However, the pathway of virus particle egress and maturation is a contentious issue. MATERIALS AND METHODS: The intracellular transport was inhibited in cultured herpes simplex virus type 1 (HSV-1) infected human fibroblasts by brefeldin A (BFA). The virus-cell interactions including the viral envelopment, transport of HSV-1 virions, and transport of viral glycoprotein D (gD-1) and glycoprotein C (gC-1) were studied by titration assay, immunoblot, immunofluorescence light microscopy, and immunogold electron microscopy of cryosections. RESULTS: gD-1 and gC-1 were synthesized and normally transported to the plasma membranes of untreated HSV-1 infected host cells. BFA (1 microg/ml medium) effectively blocked the transport of the glycoproteins to the plasma membranes and affected the tubulin and vimentin of the cytoskeleton. Viral particles and glycoproteins accumulated in the perinuclear space and the endoplasmic reticulum of BFA treated cells. Withdrawal of BFA influence up to 9 hr resulted in restored tubulin and vimentin, transport of glycoproteins to the plasma membranes, and steady release of infectious viral particles to the extracellular space superior to the cellular assembly of new virions. The ultrastructural data presented support that the primary envelopment of viral particles occur at the nuclear membranes containing immature glycoproteins followed by multiple de-envelopments and re-envelopments of the virions during the transport and maturation in the endoplasmic reticulum and the Golgi complex. CONCLUSIONS: BFA-induced changes include the cytoskeleton with significant effect on HSV-1 maturation and egress. The data support a multiple-step envelopment of HSV-1 in a common pathway of glycoprotein synthesis and virion egress.