Elimination of HPV-associated oropharyngeal cancers in Nordic countries

Incidence of human papillomavirus (HPV, most notably HPV type 16) associated oropharyngeal squamous cell carcinoma (OPSCC) among middle-aged (50?69 year-old) males has tripled in four high income Nordic countries (Denmark, Finland, Norway and Sweden) over the last 30 years. In Finland and Sweden, this increase was preceded by an HPV16 epidemic in fertile-aged populations in the 1980?s. The recent implementation of school based prophylactic HPV vaccination in early adolescent boys and girls will gradually decrease the incidence, and eventually eliminate the HPV-associated OPSCCs (especially tonsillar and base of tongue carcinomas) in the Nordic countries. However, beyond the adolescent and young adult birth cohorts vaccinated, there are approximately 50 birth cohorts (born in 1995 or before) that would benefit from screening for HPV-associated OPSCC. This article reviews the need, prerequisites, proof-of-concept trial and prospects of preventing HPVassociated OPSCC in the Nordic countries.Peer reviewe

The IARC perspective on cervical cancer screening

In May 2018, the World Health Organization (WHO) called for a global initiative to eliminate cervical cancer as a public health problem. To achieve this goal, global scale-up of effective vaccination against the human papillomavirus (HPV) as well as screening for and treatment of cervical cancer are required. Cervical cancer screening was evaluated in 2005 by the International Agency for Research on Cancer (IARC) Handbooks program,1 and a reevaluation was deemed to be timely given the major advances in the field since then. The new handbook provides updated evaluations of the effectiveness of screening methods, which were used as a basis for the update of the WHO Guideline for Screening and Treatment of Cervical Pre-cancer Lesions for Cervical Cancer Prevention.2 We convened an IARC Working Group of 27 scientists from 20 countries to assess the evidence on the current approaches to and technologies used in cervical cancer screening with the use of the newly updated Handbooks Preamble3 (Fig. 1) and Table 1).Fil: Bouvard, Véronique. International Agency For Research On Cancer; FranciaFil: Wentzensen, Nicolas. National Cancer Institute; Estados UnidosFil: Mackie, Anne. Public Health England; Reino UnidoFil: Berkhof, Johannes. University of Amsterdam; Países BajosFil: Brotherton, Julia. VCS Foundation; Australia. University of Melbourne; AustraliaFil: Giorgi Rossi, Paolo. Azienda Unità Sanitaria Locale Di Reggio Emilia; ItaliaFil: Kupets, Rachel. University of Toronto; CanadáFil: Smith, Robert. American Cancer Society; Estados UnidosFil: Arrossi, Silvina. Centro de Estudios de Estado y Sociedad; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bendahhou, Karima. Casablanca Cancer Registry; MarruecosFil: Canfell, Karen. The University Of Sydney; AustraliaFil: Chirenje, Z. Mike. University Of Zimbabwe; ZimbabueFil: Chung, Michael H.. University of Emory; Estados UnidosFil: del Pino, Marta. Hospital Clinico de Barcelona; EspañaFil: de Sanjosé, Silvia. Program for Appropriate Technology in Health; Estados UnidosFil: Elfström, Miriam. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Franco, Eduardo L.. McGill University; CanadáFil: Hamashima, Chisato. Teikyo University; JapónFil: Hamers, Françoise F.. French National Public Health Agency; FranciaFil: Herrington, C. Simon. University of Edinburgh; Reino UnidoFil: Murillo, Raúl. Hospital Universitario San Ignacio; ColombiaFil: Sangrajrang, Suleeporn. National Cancer Institute; TailandiaFil: Sankaranarayanan, Rengaswamy. Research Triangle Institute; Estados UnidosFil: Saraiya, Mona. Centers for Disease Control and Prevention; Estados UnidosFil: Schiffman, Mark. National Cancer Institute; Estados UnidosFil: Zhao, Fanghui. Chinese Academy of Medical Sciences & Peking Union Medical College; ChinaFil: Arbyn, Marc. Sciensano; BélgicaFil: Prendiville, Walter. International Agency For Research On Cancer; FranciaFil: Indave Ruiz, Blanca I.. International Agency For Research On Cancer; FranciaFil: Mosquera Metcalfe, Isabel. International Agency For Research On Cancer; FranciaFil: Lauby Secretan, Béatrice. International Agency For Research On Cancer; Franci

Advances in cervical cancer prevention: Efficacy, effectiveness, elimination?

With major advances in understanding the infectious etiology of cervical cancer, preventive medicine has obtained highly promising new tools. Human papillomavirus (HPV) vaccines, together with a growing arsenal of HPV-based screening tests, have the potential to radically change public health but require diligent, large-scale implementation to reach the final goal: the elimination of cervical cancer. We reflect here upon the state of cervical cancer prevention globally as there have been several recent developments that will inform this implementation process

HPV-mRNA and HPV-DNA detection in samples taken up to seven years before severe dysplasia of cervix uteri

Randomized clinical trials using human papillomavirus (HPV) DNA testing have found increased protection against cervical cancer and HPV-based screening is globally recommended for women ≥30 years of age. HPV-mRNA is a promising alternative target for cervical screening tests, but assessing equivalence requires longitudinal evaluation over at least the length of a screening interval. Our aim is to analyze the longitudinal sensitivity of HPV-mRNA and HPV-DNA in cervical samples taken up to 7 years before severe cervical intraepithelial neoplasia or worse (CIN3+). From a population-based cohort of 95,023 women in Sweden, cervical samples were frozen at −80°C between May 2007 and January 2012. Registry linkages identified that 1,204 of these women had CIN3+ 4 months to 7 years after enrolment. Baseline samples were analyzed for HPV-mRNA (Aptima, Hologic) and for HPV-DNA (Cobas 4800, Roche) and results from both tests obtained for 1,172 women. For both women <30 and ≥ 30 years, HPV-mRNA had similar sensitivity for CIN3+ as HPV-DNA (p = 0.0217 and p = 0.0123 in noninferiority testing for at least 90% relative sensitivity, respectively). Among women ≥30 years, the longitudinal sensitivities for CIN3+ occurring 5–7 years later were comparable [76.3% (95% CI: 65.8%–84.3%) and 82.5% (95% CI: 72.6%–89.4%)] as were the longitudinal negative predictive values for absence of CIN3+ [99.97% (95% CI: 99.95–99.98) and 99.98% (95% CI: 99.96–99.99)], for the HPV-mRNA and HPV-DNA test. In conclusion, HPV-mRNA testing has similar longitudinal sensitivity as HPV-DNA, implying that HPV-mRNA testing can safely be used for cervical screening

Cervical cancer screening in Sweden 2014-2016.

BACKGROUND:To enable incremental optimization of screening, regular reporting of quality indicators is required. AIM:To report key quality indicators and basic statistics about cervical screening in Sweden. METHODS:We collected individual level data on all cervical cytologies, histopathologies, human papillomavirus tests and all invitations for cervical screening in Sweden during 2013-2016. RESULTS:There were over 2,278,000 cervical samples collected in Sweden in 2014-2016. Organized samples (resulting from an invitation) constituted 69% of samples. The screening test coverage of all resident women aged 23-60 was 82%. The coverage has slowly increased for >10 years. There is large variability between counties (from 71% to 92%) over time. There were 25,725 women with high-grade lesions in cytology during 2013-2015. Only 96% of these women had a follow-up histopathology within a year. Cervical cancer incidence showed an increasing trend. CONCLUSION:Key quality indicators such as population coverage and follow-up rates were stable or improving, but there was nevertheless an unexplained cervical cancer increase

Comparison of the estimated annual rates of waning immunity for 13 high-risk types of HPV with those estimated by Bogaards et al.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049614#pone.0049614-Bogaards1" target="_blank">[<b>22</b>]</a><b>.</b> The vertical line signifies the average of the posterior median estimates across all types in both studies.</p

Annual rates of clearance of HPV infection.

<p>(A) Comparison of the estimated annual rates of clearance of initial HPV-16 infection in this and six further studies. The vertical line signifies the median of the median values of all seven studies. (B) Comparison of the estimated annual rates of clearance of initial HPV-18 infection in this and five further studies. The vertical line signifies the median of the median values of all six studies. (C) Comparison of the estimated annual rates of clearance of initial HPV-31 infection in four further studies. The vertical line signifies the median of the median values of all five studies.</p

The <i>Susceptible-Infectious-Recovered-Susceptible</i> (SIRS) model of high-risk Human Papillomavirus (HPV) transmission and potential consequent progression to cervical cancer.

<p>Susceptible individuals become infected at a rate proportional to the force of infection λ. Following infection, they may progress in a stepwise fashion to neoplastic lesions of increasing severity (CIN1, CIN2, CIN3) and then to cancer (with rates ). Alternatively, they may spontaneously clear the infection from any pre-cancerous stage (with rates ). High-grade clinical lesions (CIN2 and CIN3) may be identified by cytological screening and successfully treated (at a rate π). Following viral clearance or successful treatment of lesions, women retain an immunity to re-infection with the same HPV type. This immunity wanes at rate κ, precipitating a return to the Susceptible compartment.</p

The estimated rates of progression and clearance of CIN1-type lesions in four high-risk HPV types.

<p>To facilitate comparison with other studies, the grouping OHR includes types -31 and -33. Results presented are the median and 95% adjusted bootstrap confidence interval. There were insufficient data available for non-16 types to be able to infer the progression rates of CIN3 to cancer and, in the case of HPV-18, the rate of progression from CIN2 to CIN3.</p