Persistent Genital Human Papillomavirus Infection as a Risk Factor for Persistent Cervical Dysplasia

Ho, Gloria Y.F.; Burk, Robert D.; Klein, S.; Kadish, Anna S.; Chang, Chee Jen; Palan, Prabhudas R.; Basu, Jayasri; Tachezy, Ruth; Lewis, Renee; Romney, Seymour L.

doi:10.1093/jnci/87.18.1365

Cited by 706 publications

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“…Infection with high-risk, [11,17,21]. Evidence suggests that, in general, cervical cancer develops only in the small proportion of women (<10%) with persistent (or latent) HPV infection [15,23]. HPV type 16 is the most commonly occurring oncogenic HPV type, and is present in y50 % of cervical cancers and high-grade cervical intraepithelial neoplasias (CIN 2/3), and in y25 % of lowgrade cervical intra-epithelial neoplasias (CIN 1).…”

Section: What Causes Cervical Cancer ? Human Papillomavirus (Hpv)mentioning

confidence: 99%

Vaccines for cervical cancer

Lowndes¹

2006

Epidemiol. Infect.

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SUMMARYThis review focuses on current and future prevention of invasive cervical cancer (ICC), the second most common cancer among women worldwide. Implementation of population-based cytological screening programmes, using the 'Pap ' smear to detect pre-cancerous lesions in the cervix, has resulted in substantial declines in mortality and morbidity from ICC in North America and some European countries. However, cases of, and deaths from, ICC continue to occur. Primary prevention of infection with high-risk human papillomavirus (HPV) types, the central causal factor of ICC, could further reduce incidence of and mortality from ICC. This is particularly the case in developing countries, which bear 80% of the burden of ICC, and where effective Pap screening programmes are extremely difficult to implement. Very promising results from several trials of synthetic HPV type-specific monovalent (HPV 16) and bivalent (HPV 16 and 18) vaccines have recently been published, showing high efficacy against type-specific persistent HPV infection and development of type-specific pre-cancerous lesions. Large-scale phase III trials of a number of such vaccine candidates are currently underway, and there is real hope that an effective vaccine capable of protecting against infection with HPV types 16 and 18 (which together account for y70% of cervical cancer cases worldwide), and thereby of preventing development of a very significant proportion of cases of ICC, could be available within the next 2 years.

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Section: What Causes Cervical Cancer ? Human Papillomavirus (Hpv)mentioning

confidence: 99%

Vaccines for cervical cancer

Lowndes¹

2006

Epidemiol. Infect.

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“…[1][2][3] Both the length of the infection and a high viral load several years before diagnosis have been shown to increase the risk of developing cervical dysplasia and carcinoma in situ (CIS). [4][5][6] Certain HLA class II alleles, such as DRB1*1501 and DQB1*0602, have been shown to increase the risk for cervical carcinoma, most strongly in HPV 16-positive carcinomas. [7][8][9][10][11][12][13] We have previously shown that the increased carcinoma risk primarily depends on that the alleles render carriers more susceptible to HPV16 infections.…”

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confidence: 99%

HLA class II allele control of HPV load in carcinoma in situ of the cervix uteri

Beskow

Moberg

Gyllensten

2005

Intl Journal of Cancer

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Human papillomavirus (HPV) infection is the most important risk factor for development of cervical carcinoma. Carriers of certain HLA class II alleles, e.g., DRB1*1501 and DQB1*0602, are more prone to HPV 16 infection and cervical carcinoma, whereas other alleles, e.g., DRB1*1301 and DQB1*0603, render carriers less susceptible to the disease. In our study comprising 484 cases and 601 controls, we examine the effect of HLA class II alleles on viral load of the oncogenic types HPV 18/45 and HPV 31 and risk of developing cervical carcinoma in situ. We find that carriers of the commonly reported protective DRB1*1301 and DQB1*0603 alleles have lower HPV 18/45 load compared to noncarriers and a lower risk of developing HPV 18/45-positive cervical carcinoma. This provides further evidence that the HLA class II-mediated immune response to HPV is important for controlling viral load and outcome of an infection. ' 2005 Wiley-Liss, Inc.Key words: HLA; human papillomavirus; viral load; cervical carcinoma HPV is the major etiologic risk factor for cervical carcinoma and is found in the majority of cervical tumors. Although infection with oncogenic forms of HPV are common among young women, less than 1% of those infected develop cervical carcinoma. [1][2][3] Both the length of the infection and a high viral load several years before diagnosis have been shown to increase the risk of developing cervical dysplasia and carcinoma in situ (CIS). [4][5][6] Certain HLA class II alleles, such as DRB1*1501 and DQB1*0602, have been shown to increase the risk for cervical carcinoma, most strongly in HPV 16-positive carcinomas. [7][8][9][10][11][12][13] We have previously shown that the increased carcinoma risk primarily depends on that the alleles render carriers more susceptible to HPV16 infections. 12 In addition, carriers of these HLA susceptibility alleles had higher HPV 16 load in their cervical smears compared to HPV 16-positive noncarriers. A plausible hypothesis is that HLA is involved in the cellular immunity against HPV. Also, HLA alleles making carriers more susceptible to HPV infections are likely to be less efficient in triggering immunity and inducing viral clearance. As a consequence, carriers of susceptibility alleles harbor higher HPV load than carriers of more efficient alleles. The relation between viral load and carcinoma development has been most extensively studied for HPV 16, presumably because it is the most prevalent HPV type in cervical tumors throughout most of the world. 1 We have previously examined the effect of HPV 18/45 and HPV 31 viral load on the risk for cervical CIS. 14 Our results showed that higher viral load of HPV 18/45 or HPV 31 increases the risk of CIS, although the risk magnitude is less than that observed for HPV 16. Therefore, it is possible that HLA alleles could influence carcinoma development by affecting viral load also for other HPV types besides HPV 16.A meta analysis demonstrated a protective effect of the DRB1*1301 and DQB1*0603 alleles against development of cervical carcinoma in 18 ...

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“…Most genital human papillomavirus (HPV) infections are transient: within 2 years of incident infection, HPV DNA becomes undetectable in approximately 90% of women (Ho et al, 1995). Moreover, not all women infected with HPV seroconvert; only about half of all HPV DNA-positive women test positive for corresponding type-specific antibodies using available assays (Kirnbauer et al, 1994;Le Cann et al, 1995).…”

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confidence: 99%

Determinants of human papillomavirus 16 serological conversion and persistence in a population-based cohort of 10 000 women in Costa Rica

et al. 2004

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Determinants of human papillomavirus (HPV)-16 serological conversion and persistence were assessed in a population-based cohort of 10 049 women in Guanacaste, Costa Rica. Serologic responses to HPV-16 were measured in 7986 women by VLP-based enzymelinked immunosorbent assay at both study enrolment (1993/94) and at 5 -7 years of follow-up. Seropositive women were defined as X5 standard deviations above the mean optical density obtained for studied virgins at enrolment (n ¼ 573). Seroconnversion (n ¼ 409), persistence (n ¼ 675), and clearance (n ¼ 541) were defined based on enrolment and follow-up serology measurements. Age-specific distributions revealed that HPV-16 seroconversion was highest among 18-to 24-year-old women, steadily declining with age; HPV-16 seropersistence was lowest in women 65 þ years. In age-adjusted multivariate logistic regression models, a 10-fold risk increase for HPV-16 seroconversion was associated with HPV-16 DNA detection at enrolment and follow-up; two-fold risk of seroconversion to HPV-16 was associated with increased numbers of lifetime and recent sexual partners and smoking status. Determinants of HPV-16 seropersistence included a 1.5-fold risk increase associated with having one sexual partner during follow-up, former oral contraceptive use, and a 3-fold risk increase associated with HPV-16 DNA detection at both enrolment and follow-up. Higher HPV-16 viral load at enrolment was associated with seroconversion, and higher antibody titres at enrolment were associated with seropersistence. (Ho et al, 1995). Moreover, not all women infected with HPV seroconvert; only about half of all HPV DNA-positive women test positive for corresponding type-specific antibodies using available assays (Kirnbauer et al, 1994;Le Cann et al, 1995). For those women who have seroconverted, however, detection of serum antibodies to HPV capsids is a valid marker of current and past type-specific HPV exposure (Wideroff et al, 1995(Wideroff et al, , 1999Carter et al, 1996;Sasagawa et al, 1998;Touze et al, 2001).We previously reported population-based seroprevalence of HPV-16, -18, -31, and -45 in our 10 000 women population-based study in Costa Rica at enrolment; we confirmed the waning detection of HPV antibodies with age and the determinants of seroprevalence to include increasing lifetime number of sexual partners and smoking (Wang et al, 2003), as similarly reported in other prevalence studies (Stone et al, 2002;Nonnenmacher et al, 2003).To extend our cross-sectional findings, we have now completed HPV-16 serology measurements at a second time point, after 5 -7 years of follow-up. Human papillomavirus 16 was selected because it accounts for the majority of cervical cancers worldwide (Munoz et al, 2003) and is the focus of immunology and vaccinology research (Lowy and Frazer, 2003). To further our understanding of HPV serology in the natural history of cervical cancer, we report here the epidemiologic characteristics and determinants of HPV-16 serologic conversion and persistence in our Guanacaste, Costa ...

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Persistent Genital Human Papillomavirus Infection as a Risk Factor for Persistent Cervical Dysplasia

Abstract: The natural history of genital HPV infection directly influences the prognosis of cervical dysplasia as measured by persistence of the lesion. Testing for HPV infection may be valuable in the clinical management of women with cervical dysplasia.

Cited by 706 publications

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Vaccines for cervical cancer

Vaccines for cervical cancer

HLA class II allele control of HPV load in carcinoma in situ of the cervix uteri

Determinants of human papillomavirus 16 serological conversion and persistence in a population-based cohort of 10 000 women in Costa Rica

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