Persistent human papillomavirus infection and cervical neoplasia

The E6 oncoprotein derived from tumour-associated human papillomaviruses (HPVs) binds to and induces the degradation of the cellular tumour-suppressor protein p53. A common polymorphism that occurs in the p53 amino-acid sequence results in the presence of either a proline or an arginine at position 72. The effect of this polymorphism on the susceptibility of p53 to E6-mediated degradation has been investigated and the arginine form of p53 was found to be significantly more susceptible than the proline form. Moreover, allelic analysis of patients with HPV-associated tumours revealed a striking overrepresentation of homozygous arginine-72 p53 compared with the normal population, which indicated that individuals homozygous for arginine 72 are about seven times more susceptible to HPV-associated tumorigenesis than heterozygotes. The arginine-encoding allele therefore represents a significant risk factor in the development of HPV-associated cancers.

Acquisition and clearance of cervical human papillomavirus (HPV) infection were analyzed among 1425 low-income women attending a maternal and child health program in São Paulo, Brazil. Specimens collected every 4 months were tested by a polymerase chain reaction protocol (MY09/11). In all, 357 subjects were positive at least once. There were 1.3% new infections per month, with 38% cumulative positivity after 18 months. Of 177 positive subjects at enrollment, only 35% remained infected after 12 months. The monthly clearance rate was higher for nononcogenic types (12.2%; 95% confidence interval [CI], 9.6-15.4) than for oncogenic HPV infections (9.5%; 95% CI, 7.5-11.9). Median retention times were 8.1 months (95% CI, 7.8-8.3) for oncogenic types and 4.8 months (95% CI, 3.9-5.6) for nononcogenic HPV infections. The mean infection durations were 8.2 and 13.5 months for nononcogenic and oncogenic types, respectively. Although a woman's age did not affect mean duration for oncogenic types (13-14 months), nononcogenic-type infections lasted longer (10. 2 months) among younger (<35 years old) than in older women (5.6 months).