Cristine Nascente Igansi

Persistence and clearance of human papillomavirus infection: a prospective cohort study.

OBJECTIVE The objective of the study was to identify epidemiological correlates for persistence and clearance of human papillomavirus (HPV) infection. STUDY DESIGN Cervical smears collected in a prospective cohort study to perform Papanicoloau cytology and HPV deoxyribonucleic acid (DNA) detection at baseline and during the follow-up. Outcomes analyzed were: (1) persistence of HPV DNA; (2) conversion; and (3) clearance of HPV. RESULTS Among 501 women the incidence of HPV was 12.3%. Thirty-four women were persistently infected with HPV, which was associated with age below 21 years at first intercourse and 4 or more sexual partners during their lifetime. In a median of 19 months, 80.7% of women had clearance of HPV, which was associated with black race, coinfection with Chlamydia trachomatis at baseline, and a history of previous Papanicoloau smear. CONCLUSION Strategies for sexual orientation may modify the rates of HPV persistence. The association of HPV clearance with a history of previous Papanicolaou smear screening highlights the importance of improving cervical screening programs. Further studies on the association of gynecological infections with HPV clearance are needed.

p16INK4a and Ki67 expression in normal, dysplastic and neoplastic uterine cervical epithelium and human papillomavirus (HPV) infection

Cellular cycle proteins like the p16(INK4a) and the Ki67 proliferation nuclear antigen have been used as oncogenicity cellular markers. The E6 and E7 oncoproteins interact with tumor suppressor genes p53 and pRb, culminating with the p16(INK4a) overexpression. The objective of this study was to evaluate the presence of HPV-DNA in 174 cervical biopsies and correlate the different histological grades with the p16(INK4a) and Ki67 immunohistochemical expression (IHC). A cross-sectional study that enrolled a total of 174 women who underwent uterine cervical biopsies between February 2003 and December 2006, in southern Brazil, was performed. Cervical smear samples were analyzed for the presence of HPV-DNA through polymerase chain reaction (PCR), and biopsy samples were examined for p16(INK4A) and Ki67 expression through IHC techniques. The presence of HPV-DNA was observed in 89% of the tested patients, among which 52% were positive for high-risk (HR) viral types [16, 18 and 31]. Regarding p16(INK4a), an expression of 69% was observed, being expressed in 100% of the high-grade squamous lesions (HSIL) and HR-HPV-DNA positives. Ki67 expression was associated with the lesion grade, being more expressive in the most severe lesions (p<0.001). p16(INK4A) and Ki67 markers coexpression was present in 86% of the samples (p<0.001), being 100% among those positive to HR-HPV-DNA with HSIL (p<0.001). The results suggest an association between the presence of HR-HPV infection and the p16(INK4a) and Ki67 expression and which is even stronger among women with HSIL.

Chlamydia trachomatis and human papillomavirus coinfection: association with p16INK4a and Ki67 expression in biopsies of patients with pre-neoplastic and neoplastic lesions

The objective of this study was to identify the frequency of coinfection by human papillomavirus (HPV) and Chlamydia trachomatis (CT) in cervical lesions and relate it with immunohistochemical expression of p16INK4a and Ki67, both oncogenicity markers. A cross-sectional study with 86 women from primary care units in southern Brazil was conducted. Cervical swabs were collected for HPV-DNA and CT-DNA detection, through the polymerase chain reaction technique (PCR). The immunohistochemical analysis was performed on biopsy cervical tissue material to identify the expression of p16INK4a and Ki67 cell cycle markers. About 83 % were positive for HPV-DNA and 19% had coinfection with CT-DNA. Among coinfected women, 56% expressed p16INK4a. There was a statistically significant association between the histological grade of the lesion and Ki67 expression. All high-grade lesions, 50% of low-grade lesions and 31% of negative biopsies expressed Ki67 (p = 0.004). A total of 37% of coinfected women expressed both markers. In conclusion, although more than half of the coinfected patients have expressed p16INK4a and more than one third have expressed both markers, these results suggest no association between those variables. However, other studies involving larger samples are necessary to corroborate such findings.