The contribution of HPV18 to cervical cancer is underestimated using high-grade CIN as a measure of screening efficiency

Bulk, Saskia; Berkhof, Johannes; Rozendaal, Lawrence; Daalmeijer, N. C. Fransen; Gök, Murat; Schipper, Frits A. de; Kemenade, Folkert J. van; Snijders, Peter J.F.; Meijer, Chris J.L.M.

doi:10.1038/sj.bjc.6603693

Cited by 21 publications

(20 citation statements)

References 17 publications

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“…On the other hand, HPV18 is rarely reported to be present at the same time as high-grade CIN is diagnosed (43)(44)(45). In an attempt to explain this paradox, it has been suggested that HPV18-associated disease rapidly progresses through the preinvasive stages of cervical neoplasia (42).…”

Section: Discussionmentioning

confidence: 99%

Disruption of the E2 Gene Is a Common and Early Event in the Natural History of Cervical Human Papillomavirus Infection: A Longitudinal Cohort Study

Collins

Constandinou-Williams

Kong

et al. 2009

Cancer Research

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Integration of high-risk human papillomavirus (HPV) types into the host-cell genome disrupts the HPV regulatory E2 protein, resulting in a loss of negative feedback control of viral oncogene expression; this disruption has been considered a critical event in the pathogenesis of cervical neoplasia, and a potential biomarker of progressive disease. However, using serial samples taken from a cohort of young women who were recruited soon after they first had sexual intercourse, we show that disruption of the E2 gene is a common and early event in the natural history of incident cervical HPV infections. The E2 gene was significantly more likely to be disrupted in women who tested positive for HPV18 in their baseline sample than in those who tested positive for HPV16 [26% versus 58%; relative risk, 2.26; 95% confidence interval (CI), 1.38-3.71; C 2 , 9.23; 1 degree of freedom (df); P = 0.002]. Among women with an intact E2 gene in their baseline sample, the median time to first detection of E2 disruption was also shorter for those who tested positive for HPV18 than HPV16 (5.7 versus 10.9 months; hazards ratio, 1.93; 95% CI, 0.84-4.44; C 2 , 2.49; 1 df; P = 0.11).This tendency for HPV18 to integrate early, coupled with the substantial reduction in viral load in HPV18-positive samples in which E2 is disrupted, may explain why HPV18-associated disease is often reported to be characterized by minor cytologic changes, which underestimate the severity of the underlying histologic abnormality. [Cancer Res 2009; 69(9):3828-32]

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Section: Discussionmentioning

confidence: 99%

Disruption of the E2 Gene Is a Common and Early Event in the Natural History of Cervical Human Papillomavirus Infection: A Longitudinal Cohort Study

Collins

Constandinou-Williams

Kong

et al. 2009

Cancer Research

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“…In these patients, HPVs 16, 52, and 58 were the three most frequently observed HPV types. Because HPV 18 is the second most frequently observed HPV genotype in cervical cancer [35], in this study, we focused on HPVs 16, 52, 58, and 18. , and 58 were classified as "other hrHPVs." Patients who were not infected with any hrHPVs were referred to as "no hrHPVs" patients.…”

Section: Patientsmentioning

confidence: 99%

“…Cytological and histological results were combined to classify the results into the following diagnoses: normal, CIN1, CIN2, CIN3, and cervical cancer. HPVs 16,18,31,33,35,39,45,51,52,56,58,59, and 68 were classified as hrHPVs. Of these, HPV 16, 18, 52, and 58 were categorized separately.…”

Section: Patientsmentioning

confidence: 99%

“…In Japan, surgical intervention to patients with CIN2 was not common, because approximately half of these patients regress within two years [12]. A prospective cohort study involving patients with cervical intraepithelial neoplasia (CIN) has demonstrated that, without treatment, approximately 20% of CIN2 patients with HPVs 16,18,31,33,35,45,52 or 58 progress to CIN3 within 5 years [12]. On the basis of the available evidence, excision strategies can be considered in patients with CIN2 as a risk-reducing treatment when the lesion is caused by these hrHPVs [13].…”

Section: Introductionmentioning

confidence: 99%

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Multistate Markov Model to Predict the Prognosis of High-Risk Human Papillomavirus-Related Cervical Lesions

Taguchi

Hara

Tomio

et al. 2020

Cancers

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Cervical intraepithelial neoplasia (CIN) has a natural history of bidirectional transition between different states. Therefore, conventional statistical models assuming a unidirectional disease progression may oversimplify CIN fate. We applied a continuous-time multistate Markov model to predict this CIN fate by addressing the probability of transitions between multiple states according to the genotypes of high-risk human papillomavirus (HPV). This retrospective cohort comprised 6022 observations in 737 patients (195 normal, 259 CIN1, and 283 CIN2 patients at the time of entry in the cohort). Patients were followed up or treated at the University of Tokyo Hospital between 2008 and 2015. Our model captured the prevalence trend satisfactory, particularly for up to two years. The estimated probabilities for 2-year transition to CIN3 or more were the highest in HPV 16-positive patients (13%, 30%, and 42% from normal, CIN1, and CIN2, respectively) compared with those in the other genotype-positive patients (3.1–9.6%, 7.6–16%, and 21–32% from normal, CIN1, and CIN2, respectively). Approximately 40% of HPV 52- or 58-related CINs remained at CIN1 and CIN2. The Markov model highlights the differences in transition and progression patterns between high-risk HPV-related CINs. HPV genotype-based management may be desirable for patients with cervical lesions.

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“…24,25,33,34 Progression probabilities from CIN1 to CIN3 and from CIN3 to cancer were type-specific. 5,19,27 The progression rate from HPV infection to CIN3 was age-dependent and assumed to be 2.5-fold higher above the age 30 than at young age. 35 The progression from CIN3 to cervical cancer was calibrated on registry data (www.ikcnet.nl) and on historical data.…”

mentioning

confidence: 99%

HPV16/18 vaccination to prevent cervical cancer in The Netherlands: Model‐based cost‐effectiveness

Coupé

Ginkel

Melker

et al. 2008

Intl Journal of Cancer

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We evaluated the cost-effectiveness of HPV16/18 vaccination for girls aged 12 years in The Netherlands in addition to cervical cancer screening. For this purpose, we developed a simulation model that describes the relation between each of the high-risk human papillomavirus (hrHPV) types and cervical disease, allowing the occurrence of multiple type-specific infections. Model parameters were derived from Dutch cohort studies, including a large population-based screening trial, and from the national cervical cancer registry. The model satisfactorily reproduced Dutch data on HPV infection and the presence of cervical lesions. For our base-case scenario in which 85% of the girls aged 12 years were vaccinated against types 16/18 (95% efficacy, lifelong protection), the model predicted a decrease of 60% in the number of cervical cancer cases and cervical cancer deaths indicating that substantial health benefits can be achieved. Health savings were robust against changes in the vaccine efficacy (varied from 85% to 98%) but savings showed a substantial reduction when the efficacy started waning 10 years after vaccination. The discounted costs per qualityadjusted life year (QALY) were € 19,500/QALY (range € 11,000 to € 25,000/QALY) and lied near the cost-effectiveness threshold of € 20,000/QALY used in The Netherlands. The simulations further showed that vaccination cannot replace screening because vaccination without screening was less effective than screening in preventing cancer in women over 40 years of age. In conclusion, our model results support the implementation of HPV16/18 vaccination in young women in addition to cervical cancer screening. ' 2008 Wiley-Liss, Inc.Key words: simulation model; human papillomavirus; cervical cancer; vaccination Infection with high-risk human papillomavirus (hrHPV) is the necessary cause of cervical cancer.1 Recently, prophylactic vaccines have come available that protect against infection with the oncogenic HPV types 16 and 18.2,3 HPV 16 and/or 18 (HPV 16/ 18) is present in 60-80% of all cervical cancer cases.4,5 Therefore, mass vaccination may have a substantial impact on the burden of cervical cancer, even in countries with organized cervical screening. The safety and efficacy of HPV16/18 vaccination has been demonstrated in several large randomized trials. 3,6,7 For women without detectable HPV16/18 DNA, an efficacy of 90-98% against HPV16/18 positive cervical intraepithelial neoplasia grade 2 and 3 (CIN2/3) was reported. In addition, some evidence for cross-protection against other HPV types was reported.3 Because of the limited follow-up, long-term efficacy is still uncertain but within the first 5 years no reduction in efficacy was observed and HPV type-specific antibody levels remained at a high level. 8To decide whether or not to introduce nationwide HPV16/18 vaccination, insight into the cost-effectiveness of vaccination is needed in addition to information on safety and efficacy. For this purpose, simulation models have been developed that predict country-specific costs...

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The contribution of HPV18 to cervical cancer is underestimated using high-grade CIN as a measure of screening efficiency

Cited by 21 publications

References 17 publications

Disruption of the E2 Gene Is a Common and Early Event in the Natural History of Cervical Human Papillomavirus Infection: A Longitudinal Cohort Study

Disruption of the E2 Gene Is a Common and Early Event in the Natural History of Cervical Human Papillomavirus Infection: A Longitudinal Cohort Study

Multistate Markov Model to Predict the Prognosis of High-Risk Human Papillomavirus-Related Cervical Lesions

HPV16/18 vaccination to prevent cervical cancer in The Netherlands: Model‐based cost‐effectiveness

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