Consistent high viral load of human papillomavirus 16 and risk of cervical carcinoma in situ: a nested case-control study

Ylitalo, Nathalie; Sørensen, Per Soelberg; Josefsson, Agnetha; Magnusson, Patrik K. E.; Andersen, Per Kragh; Pontén, Jan; Adami, Hans‐Olov; Gyllensten, Ulf; Melbye, Mads

doi:10.1016/s0140-6736(00)02402-8

Cited by 303 publications

(259 citation statements)

References 24 publications

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“…Although controversial, HPV has also been proposed as a risk factor for oesophageal cancer (Galloway and Daling, 1996) as well as for head and neck cancers (Mork et al, 2001). However, if altered immune function entails activation of HPV infection and thereby increased viral load, an excess risk of malignancies of the cervix should be expected (Ylitalo et al, 2000), but no convincing excess was observed. This leads us to hypothesise that anatomic differences in immunologic control of HPV-harbouring target cells explains the spectacular differences in risk for HPV-associated malignancies.…”

Section: Discussionmentioning

confidence: 99%

Cancer risk following organ transplantation: a nationwide cohort study in Sweden

et al. 2003

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A substantial excess risk of lymphomas and nonmelanoma skin cancer has been demonstrated following organ transplantation. Large sample size and long follow-up time may, however, allow more accurate risk estimates and detailed understanding of long-term cancer risk. The objective of the study was to assess the risk of cancer following organ transplantation. A nationwide cohort study comprising 5931 patients who underwent transplantation of kidney, liver or other organs during 1970 -1997 in Sweden was conducted. Complete follow-up was accomplished through linkage to nationwide databases. We used comparisons with the entire Swedish population to calculate standardised incidence ratios (SIRs), and Poisson regression for multivariate internal analyses of relative risks (RRs) with 95% confidence intervals (CI). Overall, we observed 692 incident first cancers vs 171 expected (SIR 4.0; 95% CI 3.7 -4.4). We confirmed marked excesses of nonmelanoma skin cancer (SIR 56.2; 95% CI 49.8 -63.2), lip cancer (SIR 53.3; 95% CI 38.0 -72.5) and of non-Hodgkin's lymphoma (NHL) (SIR 6.0; 95% CI 4.4 -8.0). Compared with patients who underwent kidney transplantation, those who received other organs were at substantially higher risk of NHL (RR 8.4; 95% CI 4.3 -16). Besides, we found, significantly, about 20-fold excess risk of cancer of the vulva and vagina, 10-fold of anal cancer, and five-fold of oral cavity and kidney cancer, as well as two-to four-fold excesses of cancer in the oesophagus, stomach, large bowel, urinary bladder, lung and thyroid gland. In conclusion, organ transplantation entails a persistent, about four-fold increased overall cancer risk. The complex pattern of excess risk at many sites challenges current understanding of oncogenic infections that might become activated by immunologic alterations.

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Section: Discussionmentioning

confidence: 99%

Cancer risk following organ transplantation: a nationwide cohort study in Sweden

et al. 2003

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“…In addition, the first smear of the controls had to be classified as cytologically normal (PAP 5 1). 5,16 First smears were reviewed by a cytotechnician blinded to case-control status. Since we did not want to exclude individuals with transient infections, controls having abnormal smears during the study period were not excluded.…”

Section: Subjectsmentioning

confidence: 99%

“…[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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“…Sun et al (2001) recently revealed that the effect of HPV infection on SIL development is dominated by the viral load, thus highlighting a potential application of viral load testing in predicting the advancement of cervical intraepithelial lesions. Ylitalo et al (2000) reported that CIN3 is associated with HPV-16-positive women who have consistently high viral loads, and Sherman et al (2002) concluded that for women with ASCUS, HPV-load testing is highly sensitive for detecting CIN3 and cancer with dramatically fewer referrals for colposcopy.…”

Section: Discussionmentioning

confidence: 99%

Clinical and economic benefit of HPV-load testing in follow-up and management of women postcone biopsy for CIN2–3

et al. 2003

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This study aimed to evaluate the clinical and economic implications of integrating human papilloma virus (HPV) load testing into the follow-up and management protocol of women postconisation for high-grade cervical intraepithelial neoplasia (CIN2 -3). We evaluated 130 suitable women: 63 were screened biannually by Pap smears ('conventional approach') and 67 also had HPV-load testing ('HPV approach'). More stringent criteria for undergoing colposcopy or reconisation were observed by the former group compared to the latter. Both approaches were analysed for cost effectiveness. There were 33 out of 67 (49.2%) colposcopic referrals and 24 out of 67 (35.8%) reconisation/hysterectomies with the 'conventional approach' compared to 9 out of 63 (14.2%) and 7 out of 63 (11.1%) with the 'HPV approach'. Cervical intraepithelial neoplasia 2 -3 residual disease was detected in 7 out of 67 (10.5%) and 7 out of 63 (11.1%) women. The 'conventional approach' had more negative colposcopic biopsies and more negative reconisation/hysterectomy histologies than the 'HPV approach'. The respective cost per detection of one case of residual disease was US$3573 and US$3485. The 'HPV approach' required fewer colposcopic and reconisation procedures to detect one case of residual CIN2 -3. Its higher positive predictive value than that of cytology provided a significant decrease in false positive rates and a reduction of US$88 per detected case.

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Consistent high viral load of human papillomavirus 16 and risk of cervical carcinoma in situ: a nested case-control study

Cited by 303 publications

References 24 publications

Cancer risk following organ transplantation: a nationwide cohort study in Sweden

Cancer risk following organ transplantation: a nationwide cohort study in Sweden

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

Clinical and economic benefit of HPV-load testing in follow-up and management of women postcone biopsy for CIN2–3

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