Factors predicting the persistence of genital human papillomavirus infections and PAP smear abnormality in HIV-positive and HIV-negative women during prospective follow-up

Abstract

As part of an extensive multi-institutional DIANAIDS study focused on assessing the risk factors, natural history, diagnosis and follow-up of genital human papillomavirus (HPV) infections in HIV-infected women, the present communication reports a sub-cohort of 142 women (89 HIV+ and 48 HIV-), followed-up for a mean of 14.07 (+/-10.84) months to analyse the factors predicting the persistence and clearance of HPV infections (polymerase chain reaction [PCR] and sequencing) and cervical Papanicolaou (PAP) smear abnormalities, using both univariate (Kaplan-Meier) and multivariate (Cox) survival analysis. The appearance of new HPV infections during the follow-up was significantly more frequent in HIV-positive than in HIV-negative women, odds ratio (OR) 8.800 (95% confidence interval [CI]: 1.199-64.611), and also the clearance rate was significantly less frequent in HIV-positive than in HIV-negative women, 69.2% vs 22.8%, respectively (OR 0.330; 95% CI: 0.163-0.670). These two groups were also markedly different with respect to the clinical course of the cervical lesions, in the frequency of progressive disease (determined by PAP smear) was higher in HIV-positive group (12/89) than in HIV-negative women (2/52) (OR 3.506; 95% CI 0.816-15.055) (P = 0.055), in whom the disease regressed more frequently than in HIV-positive women (13.5% vs 7.9%) (OR 0.584; 95% CI 0.217-1.573). Using (1) HPV-positivity, (2) oncogenic HPV-type and (3) significant PAP smear abnormality at the end of follow-up as outcome measures, (1) was significantly (P < 0.001) predicted by the following variables in univariate analysis: age, mode of contraception, CD4 count, and HIV-positivity. The significant predictors of (2) were age and mode of contraception. The outcome measure (3) was significantly predicted by CD4 count, PAP smear abnormality and PCR status at entry. In the multivariate analysis, the significant independent predictive factors for HPV-positivity proved to be only the HIV status (P < 0.001), and PCR status at entry, p53 polymorphism at aa-72, oncogenic HPV type and significant PAP smear at entry remained independent predictors, with the significance level of P < 0.05. None of the significant predictors of oncogenic HPV type in univariate analysis retained their independent value in multivariate analysis. Oncogenic HPV type at entry proved to be an independent predictor of significant PAP smear (P < 0.05). The present results indicate that HIV-infected women, even on highly active antiretroviral therapy, demonstrate a more aggressive clinical course of cervical HPV infections, and fail to eradicate the disease more frequently than HIV-negative women. This persistence of HPV-positivity, oncogenic HPV type and significant PAP smear abnormality can be predicted by the results of PAP test and HPV typing in univariate analyses, and partly retain their independent predictive value also in multivariate analysis. Clearly, in addition to regular monitoring by PAP smear, HPV testing for the oncogenic HPV types seems to provide additional prognost...

A Study of Pap Smears in HIV-Positive and HIV-Negative Women from a Tertiary Care Center in South India

“…A higher incidence of epithelial cell abnormalities were observed in HIV-positive women with lower CD4 cell counts as compared to the HIV-negative control group. However, there was no association of CD4 cell counts with epithelial cell abnormalities on Pap smears as observed by other researchers [3, 4, 7, 9]. This could be due to a smaller sample size in the present study.…”

“…HIV-infected females are more likely to show abnormal Pap smear results such as squamous cell carcinoma (SCC), high-grade squamous intraepithelial lesion (HSIL) and low-grade squamous intraepithelial lesions (LSIL) [4]. In a landmark multi-institutional study by Branca et al [7], the researchers studied various risk factors, clinical course, and follow-up in patients infected with HIV. They concluded that there was an increased risk of development of cervical cancer in cases exhibiting significant Pap smear abnormalities and were of the view that therapeutic intervention was mandated in such cases.…”

Risk factors for HPV infection and cervical cancer among unscreened women in a high-risk rural area of China

“…28 It seems that the high rates of HPV, CIN and CC in the South African series were, in part, due to the HIV-positive rate, because persistence of HPV is much more likely in HIV-positive than in HIV-negative women. 29 The overall rate of HPV positives in SPOCCS II was significantly higher than the 18% prevalence rate in SPOCCS I conducted in other parts of one (Xiangyuan) of 2 counties (v 2 5 6.8, p 5 0.01), whereas the rates of CIN II1 were similar (4.4% vs. 4.3%). 30 The rates of HPV infection in SPOCCS I and II were 18% and 18.6%, respectively among women in Xiangyuan County screened in Summer, however, thereby removing the season and county effects (Fig.…”

Cervical Cancer Screening and Prevention for HIV-Infected Women in the Developing World

“…Studies have shown that HIV-infected women have higher prevalence of HPV, higher incidence of HPV (Branca 2003;, higher HPV viral load (Jamieson 2002), longer persistence of HPV (Ahdieh 2000;Sun 1997), higher likelihood of multiple HPV subtypes (Jamieson 2002;Firnhaber et al 2009;Clifford et al 2007), and greater prevalence of oncogenic subtypes (Minkoff 1998;Uberti-Foppa 1998;Acta Cytol 2009;53: 10-17) than HIVuninfected women. HPV viral load is independently associated with HPV persistence .…”