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

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 predicted endemic prevalence of type-specific HPV infection in sexually active women and the observed prevalence in both women attending voluntary Chlamydia screening (solid dots) and those tested at baseline in the Swedescreen study (hollow dots).

<p>The median predicted prevalence for each type is represented by the solid curve and the turquoise bands represent the 50%, 70%, 90% and 95% posterior intervals.</p

Estimated rates of progression to disease.

<p>(A) The estimated rates of progression of infection with HPV-16, HPV-18 and other high-risk (OHR) HPV types to CIN1-type lesions. We compare the rates estimated from the longitudinal Swedescreen data with the model-based estimates of Jit et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049614#pone.0049614-Jit1" target="_blank">[5]</a> and Van de Velde et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049614#pone.0049614-VandeVelde1" target="_blank">[21]</a>. (B) The estimated rates of progression of CIN1-type lesions attributable to HPV-16, HPV-18 and other high-risk (OHR) HPV types to CIN2-type lesions. We compare the rates estimated from the longitudinal Swedescreen data with the model-based estimates of Jit et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049614#pone.0049614-Jit1" target="_blank">[5]</a> and Van de Velde et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049614#pone.0049614-VandeVelde1" target="_blank">[21]</a>.</p

Comparison of the estimated annual rates of clearance of initial infection between 13 high-risk HPV types and HPV-6 and -11.

<p>The vertical line signifies the median of the median rates for all fifteen types; horizontal bars represent the 95% posterior intervals.</p

Minor Cytological Abnormalities and up to 7-Year Risk for Subsequent High-Grade Lesions by HPV Type.

OBJECTIVE:Diagnoses of atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) are common, but the corresponding risk of disease varies by human papillomavirus (HPV) status, complicating management strategies. Our aim was to estimate the longer-term risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) among women with ASCUS/LSIL by age, HPV status, and genotype(s). METHODS:A total of 314 women with ASCUS/ LSIL were followed for a median of 3.8 years. Baseline HPV status was determined by reflex testing and women with histologically confirmed CIN2+ were identified through linkage to the Swedish National Quality Register for Cervical Cancer Prevention. Cumulative incidence and hazard ratios were estimated to explore differences between index data and associations with CIN2+. RESULTS:In total, 89 women (28.3%) developed CIN2+. High-risk (HR) HPV-positive women developed significantly more CIN2+ than HR-HPV-negative women (cumulative incidence 3.5 years after the index test: 42.2%, 95% CI: 32.5-53.5 for HPV16/18; 36.2%, 95% CI: 28.3-45.4 for other HR-HPV types; and 2.0%, 95% CI: 0.5-7.8 for HR-HPV-negative women; p<0.0001). CONCLUSION:HPV status was of greatest importance in determining the risk of CIN2+. The risk was low among HPV-negative women during the first years of follow-up, suggesting these women could be followed less intensively. HPV16/18-positive women may need intensified follow-up as they showed the highest risk of CIN2+