Cervical squamous intraepithelial lesions of low-grade in HIV-infected women: Recurrence, persistence, and progression, in treated and untreated women
ABSTRACT Human immunodeficiency virus (HIV)-infected patients are more predisposed than HIV-negative women to develop squamous intraepithelial lesions (SIL) of the uterine cervix, and cervical dysplasia may be of higher grade in HIV-positive women than in HIV-negative subjects, with more extensive and multi-centric involvement of the lower genital tract by human papillomavirus (HPV)-associated lesions. Moreover, recurrence and progression rate of cervical intraepithelial neoplasia (CIN) is particularly higher in immunocompromised women.
Retrospective case-control study of HIV-positive women and HIV-negative controls, all affected by low-grade SIL of the uterine cervix, treated by loop excision or followed-up without treatment. Correlation of progression and recurrence of SIL with HIV status and CD4+ count.
From September 1990 to October 1997, 75 HIV-positive low-grade-SIL patients, 47 treated and 28 followed-up without treatment, and 75 HIV-negative low-grade-SIL controls, 45 treated and 30 followed-up.
Among treated patients, 17/47 (36.2%) HIV-positive and 5/45 (11.1%) controls had recurrence (P < 0.0101, O.R. = 4.53, 95% CI = 1.5-13.7), progression of untreated lesion was seen in 15/28 (53.6%) HIV-positive and 7/30 (23%) controls (P < 0.05, O.R. = 3.79, 95% CI = 1.23-11.69). The risk of recurrence or progression of low-grade SIL linked to HIV seropositivity is about 4-5 times higher in comparison with seronegative counterpart, matched for age, risk factors and lesion size. More significantly, considering the cut-off of 200 CD4+/mm(3) in HIV-positive women, 13/17 cases of recurrence (P < 0.05, O.R. = 4.88, 95% CI = 1.28-18.58) and 10/15 cases with progression (P < 0.05, O.R. = 6.67, 95% CI = 1.24-35.73) were immunocompromised (<200 CD4+/mm3), with a significant higher risk of recurrence or progression linked to immunodeficiency status. Considering time of progression or recurrence, during follow-up, Kaplan-Meier curves shows that HIV-positive status and immunodeficiency are correlated with more rapid evolution of cervical dysplasia and HPV-related lesions: comparison of recurrence in treated patients report P < 0.005 and progression in untreated P<0.05 (Mantel-Haenszel log-rank test).
Immunological status seems to be a determinant factor in prognosis of cervical SIL, HIV-positive women affected by this lesion, even if low-grade, need more aggressive management than the immunocompetent counterpart. Strict cytologic and colposcopic screening is recommended and CD4+ count and HPV-DNA testing may be useful risk indicators. Excisional procedures are preferred, while ablative treatments or wait and see policy may expose to some risk this type of population with poor compliance to follow-up.
- SourceAvailable from: Hiroshi Ichimura
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- "Furthermore , compared to their non-infected counterparts, women infected with HIV and who develop cervical cancer are more likely to present with advanced clinical disease [Maiman et al., 1997]. The high prevalence of HPV among women who are HIVpositive can be explained by the tendency for HPV to persist, thus differing from what occurs among immunocompetent individuals [Nappi et al., 2005; Hawes et al., 2006; Palefsky, 2006b; Berrebi et al., 2008; Denny et al., 2008]. "
ABSTRACT: The aim of this study was to investigate an association between certain human papillomavirus (HPV) types and human immunodeficiency virus (HIV) infections. Sexually active females (n = 487; 19-61 years old) were enrolled in the study. Subjects underwent Pap testing and evaluations of HIV and HPV infection status on uterine cervical cell samples. HPV genotyping was performed using a Kurabo GeneSQUARE DNA microarray test. Overall, 23 HPV genotypes were detected, and the most prevalent HPV genotype was HPV-52, followed by HPV-39, -54, -45, -56, -53, -31, -42, -16, -68, and -51. HPV-30, -53, -54, -61, and -66, which are associated with abnormal cytology, are categorized as intermediate-risk in this study. Detection of both high- and intermediate-risk HPV types was significantly associated with cervical abnormality and HIV infection. Multivariate analysis revealed that some high-risk HPV types (HPV-31, -45, -51, -56, and -59) and most intermediate-risk HPV types were associated with HIV infection, while the high-risk types (HPV-16, -18, -33, -35, -39, -52, -58, and -68) were not. The oncogenic effect of the most malignant HPV types (e.g., HPV-16 and -18) appear to be lower, while that of intermediate-risk types are greater, in areas with a high prevalence of HIV infection.Journal of Medical Virology 11/2011; 83(11):1988-96. DOI:10.1002/jmv.22203 · 2.22 Impact Factor
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ABSTRACT: The purpose of the present study was to examine the outcome of pregnancies among HIV-infected women in Helsinki, use of the levonorgestrel-releasing intrauterine system (LNG-IUS) among HIV-infected women and the prevalence and risk factors of cytological and histologically proven cervical lesions in this population. Between 1993 and 2003 a total of 45 HIV-infected women delivered 52 singleton infants. HIV infection was diagnosed during pregnancy in 40% of the mothers. Seventeen of the mothers received antiretroviral (ARV) medication prior to pregnancy and in 34 cases, the medication was started during pregnancy. A good virological response (i.e. HIV RNA load <1000/mL during the last trimester) to ARV medication was achieved in 36/40 (90%) of the patients in whom HI viral load measurements were performed. Of the infants, 92% were born at term, and their mean (±SD) birth weight was 3350±395 g. The Caesarean section rate was low, 25%. All newborns received ARV medication and none of the infants born to mothers with pre-delivery diagnosis of maternal HIV infection were infected. The safety and advantages of the LNG-IUS were studied prospectively (n=12) and retrospectively (n=6). The LNG-IUS was well tolerated and no cases of PID or pregnancy were noted. Menstrual bleeding was reduced significantly during use of the LNG-IUS; this was associated with a slight increase in haemoglobin levels. Serum oestradiol concentrations remained in the follicular range in all subjects. The key finding was that genital shedding of HIV RNA did not change after the insertion of the LNG-IUS. The mean annual prevalence of low-grade squamous intraepithelial lesions (SIL) was 15% and that of high-grade SIL was 5% among 108 systematically followed HIV-infected women during 1989 2003. A reduced CD4 lymphocyte count was associated with an increased prevalence of SIL, whereas duration of HIV infection, use of ARV medication and HI viral load were not. The cumulative risk of any type of SIL was 17% after one year and 48% after five years among patients with initially normal Pap smears. The risk of developing SIL was associated with young age and a high initial HI viral load. During the follow-up 51 subjects (n=153) displayed cervical intraepithelial neoplasia (CIN), (16% CIN1 and 18% CIN 2-3). Only one case of cancer of the uterine cervix was detected. Pap smears were reliable in screening for CIN. Both nulliparity (p<0.01) and bacterial vaginosis (p<0.04) emerged as significant risk factors of CIN. In conclusion, a combination of universal antenatal screening and multidisciplinary management allows individualized treatment and prevents vertical transmission of HIV. Use of the LNG-IUS is safe among HIV-infected women and cervicovaginal shedding of HIV RNA is not affected by use of the LNG-IUS. The risk of cervical pre-malignant lesions is high among HIV-infected women despite systematic follow-up. WHO:n tilastojen mukaan maailmassa on jo lähes 40 miljoonaa HIV-positiivista ihmistä. Epidemian alussa HIV-infektiota pidettiin vain homoseksuaalisten miesten tautina, mutta nykyisin naisia on jo lähes puolet sairastuneista. Suomessa todettiin 60 uutta HIV-infektiota naisilla vuonna 2006; aiempina vuosina luku on ollut 20 40. HIV-infektioon liittyy naisilla erityisiä haasteita ja ongelmia: - vaikutukset raskauksiin ja sikiön tartuntariski - hormonaalisen ja kierukkaehkäisyn aiheuttama kohdunkaulan viruserityksen kasvu -lisääntynyt kohdunkaulan solumuutosten ja kohdunkaulan syövän riski. Väitöskirjatyössä selviteltiin HIV-positiivisten naisten raskauksien kulku ja lapsen ennuste kymmenen vuoden ajalta Helsingin Naistenklinikalla, levonorgestreeliä erittävän hormonikierukan edut ja turvallisuus sekä kohdunkaulan solu- ja kudosmuutosten esiintyvyys ja riskitekijät. Vuosina 1993 2003 HIV-positiivisten naisten synnytyksiä oli 52. Naisista 40 % sai tietää HIV-positiivisuudestaan ensi kertaa alkuraskauden seulontatestissä. Raskaudenaikaiselle HI-virus-lääkitykselle vaste oli hyvä; 90 %:lla naisista loppuraskauden virusmäärät olivat alle 1000 kopiota/mL. Lapset syntyivät hyväkuntoisina ja keskikokoisina. Sektioprosentti oli matala (25 %); monissa Euroopan maissa se on kohonnut 90 %:iin. Kukaan lapsista ei saanut tartuntaa. Hormonikierukka todettiin turvalliseksi HIV-positiivisilla naisilla. Raskauksia tai infektioita ei esiintynyt. Kuukautisvuodon määrä väheni ja veren hemoglobiini-pitoisuudet nousivat. Päähavainto oli, että kohdunkaulan viruseritys säilyi samanlaisena ennen ja jälkeen hormonikierukan laiton, eikä sen käyttö täten näytä lisäävän tartuntariskiä. Papa-näytteiden solumuutosten vuosittainen esiintyvyys oli korkea; lievien muutosten 15 % ja vaikeiden muutosten 5 %. Samaan aikaan valtakunnallisessa papa-seulonnassa vastaavia muutoksia esiintyi 1,6 %:lla seulotuista. Matala CD4-solutaso osoittautui riskitekijäksi näille muutoksille. Riski papa-muutoksille oli vuoden jälkeen 17 % ja viiden vuoden jälkeen 48 % niillä naisilla, joilla seurannan alussa oli normaali papa-koe. Nuori ikä ja korkeat HI-virusmäärät lisäsivät papa-muutosten riskiä. Kohdunkaulan koepalanäytteissä 51 naisella esiintyi patologisia muutoksia; HIV-positiivisia naisia oli seurannassa 153. Yksi kohdunkaulan syöpä todettiin seurannan aikana. Sekä synnyttämättömyys että emättimen bakterielli tulehdus lisäsivät kudosmuutosten riskiä. Yhteenvetona: - HIV-seulonta alkuraskaudessa, HI-viruslääkitys raskauden aikana ja synnytysten yksilöllinen hoito ovat tehokkaita keinoja sikiön tartunnan ehkäisemiseksi - hormonikierukka on turvallinen ja tehokas ehkäisykeino HIV-positiivisilla naisilla - kohdunkaulan solu- ja kudosmuutosten esiintyvyys on korkea myös systemaattisesti seuratuilla HIV-positiivisilla naisilla.
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ABSTRACT: Human immunodeficiency virus (HIV)-positive women are at high risk of co-infection from human papillomavirus (HPV) and of developing squamous intraepithelial lesions of the cervix. From April 1997 to March 1999, 86 women, affected by high-grade squamous intra-epithelial lesions (H-SILs), were enrolled: 41 were HIV+ (CD4+ count >500/ml) and 45 were HIV-. The diagnosis of high-grade squamous intra-epithelial lesion (H-SIL) was established for each patient by Pap test, colposcopy and guided biopsy. For all samples, the HPV/DNA test was also performed by PCR. The patients' lesions and recurrence were treated by cone biopsy or large loop excision (LEEP). Annual controls were performed for 5 years. A high rate of alcohol and drug use (60.7% vs. 31.4%; p=0.004; 80% vs. 27.5%; p<0.001, respectively) and number of male partners (4.5 vs. 3.0; p<0.001) were found in the HIV+ patients, compared to the HIV- patients. Both groups were HPV+ for high-risk types. No difference was found in the percentage of patients who had received a second LEEP. Our findings suggest the treatment of H-SIL in HIV-positive women, for a longer disease-free survival, or a lower risk of developing cervical cancer.Anticancer research 07/2006; 26(4B):3167-70. · 1.87 Impact Factor