Human papillomavirus type-specific risk of cervical cancer in a population with high human immunodeficiency virus prevalence: case-control study.
ABSTRACT There are limited data on human papillomavirus (HPV) type-specific cervical cancer risk among human immunodeficiency virus (HIV)-positive women. Previous studies have suggested that HPV 16 would be relatively less important as a causative agent among HIV-positive compared with HIV-negative women. This study investigates HPV type-specific cervical cancer risk in a population in which HIV is endemic. At the Central Hospital, Maputo, Mozambique, 221 cervical cancer cases and 203 hospital-based controls were consecutively enrolled. HPV typing from cervical samples, HIV testing and recording of socio-demographic factors were performed. Logistic regression modelling was used to assess HPV type-specific risk and effect modification between HIV and HPV infection. Infection with HPV 16, 18 and 'high-risk non-HPV 16/18 types' (HPV 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59) was associated with cervical cancer in both crude and adjusted analyses. HPV 16 and 18 were the most common types detected in cancer biopsies among both HIV-negative and HIV-positive women. There was no significant evidence of effect modification between any HPV type and HIV infection, and there were no significant differences in the HPV type-specific prevalence when cervical cancers among HIV-positive and HIV-negative women were compared. Within the limitations of the study, the relative importance of different HPV types in cervical carcinogenesis appears not to be modified greatly by HIV infection, suggesting that HPV vaccines might not need to be type-specifically modified to be suitable for populations where HIV is endemic.
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ABSTRACT: Among women infected with the human immunodeficiency virus (HIV), there is a high prevalence of human papillomavirus (HPV) infections. However, little is known about the natural history of HPV infections in HIV-seropositive women, and persistent HPV infections may explain the increased risk of cervical squamous intraepithelial lesions and invasive cervical cancer in HIV-seropositive women. A total of 220 HIV-seropositive and 231 HIV-seronegative women in the New York City area were evaluated at two or more semiannual gynecologic examinations that included a Pap test, a test for HPV DNA, and colposcopy. HPV DNA was detected at the initial examination in 56 percent of the HIV-seropositive and 31 percent of the HIV-seronegative women. After four examinations, the cumulative prevalence of HPV infection was 83 percent in the seropositive women and 62 percent in the seronegative women (P<0.001). Persistent HPV infections were found in 24 percent of the seropositive women but in only 4 percent of the seronegative women (P<0.001). Twenty percent of the seropositive women and 3 percent of the seronegative women had persistent infections with HPV-16-associated viral types (16, 31, 33, 35, or 58) or HPV-18-associated types (18 or 45) (P<0.001), which are most strongly associated with cervical cancer. The detection of HPV DNA in women with previously negative tests was not associated with sexual activity during the interval since the preceding examination. HIV-seropositive women have a high rate of persistent HPV infections with the types of HPV that are strongly associated with the development of high-grade squamous intraepithelial lesions and invasive cervical cancer. These persistent infections may explain the increased incidence of squamous intraepithelial lesions in HIV-seropositive women.New England Journal of Medicine 12/1997; 337(19):1343-9. · 51.66 Impact Factor
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ABSTRACT: Human papillomavirus (HPV) can be detected by amplification of viral DNA. A novel PCR primer set generating a short PCR fragment (SPF PCR) was used for amplification of a fragment of only 65 bp from the L1 region and permitted ultrasensitive detection of a broad spectrum of HPV genotypes. The intra- and intertypic sequence variations of the 22-bp interprimer region of this amplimer were studied. Among 238 HPV sequences from GenBank and clinical specimens, HPV genotypes were correctly identified based on the 22-bp sequence in 232 cases (97.2%). Genotype-specific probes for HPV genotypes 6, 11, 16, 18, 31, 33 to 35, 39, 40, 42 to 45, 51 to 54, 56, 58, 59, 66, 68, 70, and 74 were selected, and a reverse hybridization line probe assay (LiPA) (the INNO-LiPA HPV prototype research assay) was developed. This LiPA permits the use of amplimers generated by the SPF as well as the MY 09/11 primers. The assay was evaluated with a total of 1, 354 clinical specimens, comprising cervical scrapes (classifications ranging from normal cytology to severe dyskaryosis) and formalin-fixed, paraffin-embedded cervical carcinoma samples. LiPA results were highly concordant with sequence analysis of the SPF amplimer, genotype-specific PCR, and sequence analysis of amplimers generated by MY 09/11 primers. The sensitivity of the SPF primers was higher than that of the GP5(+)/6(+) primers over a broad range of HPV types, especially when multiple HPV genotypes were present. In conclusion, the SPF LiPA method allows extremely sensitive detection of HPV DNA as well as reliable identification of HPV genotypes in both cervical smears and paraffin-embedded materials.Journal of Clinical Microbiology 09/1999; 37(8):2508-17. · 4.07 Impact Factor
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ABSTRACT: A recent report that 93 per cent of invasive cervical cancers worldwide contain human papillomavirus (HPV) may be an underestimate, due to sample inadequacy or integration events affecting the HPV L1 gene, which is the target of the polymerase chain reaction (PCR)-based test which was used. The formerly HPV-negative cases from this study have therefore been reanalyzed for HPV serum antibodies and HPV DNA. Serology for HPV 16 VLPs, E6, and E7 antibodies was performed on 49 of the 66 cases which were HPV-negative and a sample of 48 of the 866 cases which were HPV-positive in the original study. Moreover, 55 of the 66 formerly HPV-negative biopsies were also reanalyzed by a sandwich procedure in which the outer sections in a series of sections are used for histological review, while the inner sections are assayed by three different HPV PCR assays targeting different open reading frames (ORFs). No significant difference was found in serology for HPV 16 proteins between the cases that were originally HPV PCR-negative and -positive. Type-specific E7 PCR for 14 high-risk HPV types detected HPV DNA in 38 (69 per cent) of the 55 originally HPV-negative and amplifiable specimens. The HPV types detected were 16, 18, 31, 33, 39, 45, 52, and 58. Two (4 per cent) additional cases were only HPV DNA-positive by E1 and/or L1 consensus PCR. Histological analysis of the 55 specimens revealed that 21 were qualitatively inadequate. Only two of the 34 adequate samples were HPV-negative on all PCR tests, as against 13 of the 21 that were inadequate ( p< 0.001). Combining the data from this and the previous study and excluding inadequate specimens, the worldwide HPV prevalence in cervical carcinomas is 99.7 per cent. The presence of HPV in virtually all cervical cancers implies the highest worldwide attributable fraction so far reported for a specific cause of any major human cancer. The extreme rarity of HPV-negative cancers reinforces the rationale for HPV testing in addition to, or even instead of, cervical cytology in routine cervical screening.The Journal of Pathology 10/1999; 189(1):12-9. · 7.59 Impact Factor