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Data on carcinogenicity of human papillomavirus (HPV) types in the anus are needed to inform anal cancer prevention through vaccination and screening. This is particularly the case for people infected with HIV, who are at an increased risk of anal cancer. We did a systematic review of studies published from January, 1986, to July, 2017, in MEDLINE, Embase, and the Cochrane Library on anal HPV infection, without any language restrictions. Eligible studies reported type-specific HPV prevalence by strata of cytopathological or histopathological anal diagnosis, sex, and HIV status. Data requests were made to authors when necessary. We did a meta-analysis of type-specific HPV prevalence across the full spectrum of anal diagnoses, from normal cytology to anal cancer. We assessed the main outcome of type-specific HPV prevalence ratios [PR], calculated across strata of anal diagnoses, gender, or HIV status, by use of generalised linear models. 95 studies were identified from the search, published between 1992–2017, from which 18 646 individuals fulfilled the criteria for inclusion in the analyses: 8534 people with normal cytology, 5730 with low-grade lesions, 2024 with high-grade lesions, and 2358 with anal cancer. HPV prevalence varied in normal cytology from 42% in HIV-negative women to 76% in HIV-positive men and, for each diagnosis, was higher in individuals who were HIV positive than those who were HIV negative. HPV16 positivity increased with diagnosis severity, being the only HPV type accounting for more HPV infection in anal cancer than normal cytology, both in individuals who were HIV negative (PR 5·0, 95% CI 3·8–6·6, p<0·0001) and those who were HIV positive (2·3, 1·9–2·7, p<0·0001). HPV16 positivity increased even between high-grade lesions and anal cancer, whereas other high-risk HPV types accounted for high proportions of low-grade or high-grade lesions but their prevalence decreased in anal cancer. However, HPV16 was less frequent in HIV-positive than HIV-negative anal cancer, both in men (PR 0·8, 95% CI 0·7–0·9, p<0·0001) and women (0·8, 0·6–1·0, p=0·063), and in HIV-positive versus HIV-negative high-grade lesions in women (0·6, 0·5–0·9, p=0·0077). Type-specific attribution of the non-HPV16 fraction of HIV-positive anal cancer is hindered by a high prevalence of multiple HPV infections. HPV16 is by far the most carcinogenic HPV type in the anus, with enrichment of HPV16 even from high-grade lesions to anal cancer, both in individuals who are HIV negative and those who are HIV positive. Nevertheless, the fraction of anal cancer attributable to HPV16 is smaller in the HIV-positive population. International Agency for Research on Cancer.

Infections with certain viruses, bacteria, and parasites have been identified as strong risk factors for specific cancers. An update of their respective contribution to the global burden of cancer is warranted. We considered infectious agents classified as carcinogenic to humans by the International Agency for Research on Cancer. We calculated their population attributable fraction worldwide and in eight geographical regions, using statistics on estimated cancer incidence in 2008. When associations were very strong, calculations were based on the prevalence of infection in cancer cases rather than in the general population. Estimates of infection prevalence and relative risk were extracted from published data. Of the 12·7 million new cancer cases that occurred in 2008, the population attributable fraction (PAF) for infectious agents was 16·1%, meaning that around 2 million new cancer cases were attributable to infections. This fraction was higher in less developed countries (22·9%) than in more developed countries (7·4%), and varied from 3·3% in Australia and New Zealand to 32·7% in sub-Saharan Africa. Helicobacter pylori, hepatitis B and C viruses, and human papillomaviruses were responsible for 1·9 million cases, mainly gastric, liver, and cervix uteri cancers. In women, cervix uteri cancer accounted for about half of the infection-related burden of cancer; in men, liver and gastric cancers accounted for more than 80%. Around 30% of infection-attributable cases occur in people younger than 50 years. Around 2 million cancer cases each year are caused by infectious agents. Application of existing public health methods for infection prevention, such as vaccination, safer injection practice, or antimicrobial treatments, could have a substantial effect on the future burden of cancer worldwide. Fondation Innovations en Infectiologie (FINOVI) and the Bill & Melinda Gates Foundation (BMGF).

Background. Data on the relative carcinogenic potential of human papillomavirus (HPV) types among women infected with human immunodeficiency virus (HIV) (WHIV) are needed to inform prevention programs for this population. Methods. A systematic literature review and meta-analysis of high-risk HPV-type distribution in 19 883 HIV-positive women was performed. The women, from 86 studies worldwide, included 11 739 with normal cytological findings; 1784 with atypical squamous cells of undetermined significance (ASCUS); 2173 with low-grade and 1282 with high-grade squamous intraepithelial lesions (HSILs) diagnosed cytologically; 1198 with cervical intraepithelial neoplasia grade 1 (CIN1), 456 with CIN2, and 455 with CIN3 diagnosed histologically; and 796 with invasive cervical cancers (ICCs). A large proportion of WHIV, and almost all with ICCs, were from Africa. Results. In Africa, HPV 16 accounted for 13% of HPV-positive WHIV with normal cytological findings, but this proportion increased through ASCUS, low-grade squamous intraepithelial lesions, CIN1, and CIN2 (18%–25%), up to 41%–47% for CIN3 and ICCs. Only HPV 16, HPV 18, and HPV 45 accounted for a greater proportion of HPV infections in ICCs compared with normal cytological findings (ICC:normal ratios, 3.68, 2.47, and 2.55, respectively). Other high-risk types accounted for important proportions of low- and/or high-grade lesions, but their contribution dropped in ICCs, with ICC:normal ratios in Africa ranging from 0.79 for HPV 33 down to 0.38 for HPV 56. Findings for HPV 16 and HPV 18 in Europe/North America, Asia, and Latin America were compatible with those from Africa. Conclusions. HPV 16 and HPV 18 in particular, but also HPV 45, at least in Africa, warrant special attention in WHIV. Broad consistency of findings with those in HIV-uninfected population would suggest that the risk stratification offered by partial HPV genotyping tests also have relevance for HIV-positive women.

Dramatic increases have been seen over recent decades in the reported incidence of thyroid cancer, but owing to new modes of screening, hundreds of thousands of cases may be overdiagnoses — diagnosis of tumors that would not, if left alone, result in symptoms or death. Several reports have described dramatic increases over recent decades in the incidence of thyroid cancer, 1 predominantly small papillary carcinomas, 2 even as thyroid-cancer–related mortality rates have not changed substantially. 3 The largest increase has been observed in South Korea: the incidence among people 15 to 79 years of age (standardized to the world population) increased from 12.2 cases per 100,000 persons in 1993–1997 to 59.9 cases per 100,000 persons in 2003–2007, 1 making thyroid cancer the most commonly diagnosed cancer among women in that country. The introduction of new diagnostic techniques (ultrasonography, computed tomography, and magnetic resonance imaging), combined with increased medical surveillance . . .

High coverage of human papillomavirus (HPV) vaccination is key to the eventual elimination of infection and cervical cancer. Monitoring coverage, in a digital vaccine registry, is therefore essential to detect problems. For example, misinformation about dangers from HPV vaccine generated in Denmark a decline in coverage among girls age 12–17, from 80% in 2013 down to 37% in 2015, when remedial actions made it rise again. The availability of human papillomavirus (HPV) vaccines and screening tests has raised the possibility of globally eliminating cervical cancer, which is caused by HPV. Cervical cancer is a very common malignancy worldwide, especially among deprived women. High vaccination coverage is key to the containment and eventual elimination of the infection. Public HPV vaccination programmes in Italy and Denmark were swiftly established and are among the most successful worldwide. Still, in both countries, it has been challenging to achieve and maintain the recommended coverage of > 80% in girls. In a well‐studied Italian region, vaccination coverage in girls at age 15 years (World Health Organization's gold standard) reached 76% in 2015 but decreased to 69% in 2018, likely due to work overload in public immunization centres. In Denmark, doubts about safety and efficacy of the HPV vaccine generated a decline in coverage among girls age 12–17, from 80% in 2013 down to 37% in 2015, when remedial actions made it rise again. Insights from these two countries are shared to illustrate the importance of monitoring coverage in a digital vaccine registry and promptly reacting to misinformation about vaccination.

Cervical cancer is caused by human papillomavirus infection. Most human papillomavirus infection is harmless and clears spontaneously but persistent infection with high-risk human papillomavirus (especially type 16) can cause cancer of the cervix, vulva, vagina, anus, penis, and oropharynx. The virus exclusively infects epithelium and produces new viral particles only in fully mature epithelial cells. Human papillomavirus disrupts normal cell-cycle control, promoting uncontrolled cell division and the accumulation of genetic damage. Two effective prophylactic vaccines composed of human papillomavirus type 16 and 18, and human papillomavirus type 16, 18, 6, and 11 virus-like particles have been introduced in many developed countries as a primary prevention strategy. Human papillomavirus testing is clinically valuable for secondary prevention in triaging low-grade cytology and as a test of cure after treatment. More sensitive than cytology, primary screening by human papillomavirus testing could enable screening intervals to be extended. If these prevention strategies can be implemented in developing countries, many thousands of lives could be saved.

Infections with human papillomavirus (HPV) are common and transmitted by direct contact. Although the great majority of infections resolve within 2 years, 13 phylogenetically related, sexually transmitted HPV genotypes, notably HPV16, cause — if not controlled immunologically or by screening — virtually all cervical cancers worldwide, a large fraction of other anogenital cancers and an increasing proportion of oropharyngeal cancers. The carcinogenicity of these HPV types results primarily from the activity of the oncoproteins E6 and E7, which impair growth regulatory pathways. Persistent high-risk HPVs can transition from a productive (virion-producing) to an abortive or transforming infection, after which cancer can result after typically slow accumulation of host genetic mutations. However, which precancerous lesions progress and which do not is unclear; the majority of screening-detected precancers are treated, leading to overtreatment. The discovery of HPV as a carcinogen led to the development of effective preventive vaccines and sensitive HPV DNA and RNA tests. Together, vaccination programmes (the ultimate long-term preventive strategy) and screening using HPV tests could dramatically alter the landscape of HPV-related cancers. HPV testing will probably replace cytology-based cervical screening owing to greater reassurance when the test is negative. However, the effective implementation of HPV vaccination and screening globally remains a challenge. Virtually all cervical cancers, a large fraction of other anogenital cancers and an increasing proportion of oropharyngeal cancers are caused by human papillomavirus (HPV) infection. Here, the authors describe HPV-driven carcinogenesis and discuss how developments in vaccines and screening tests could dramatically alter the landscape of HPV-related cancers worldwide.

► 1 in 10 women worldwide carries an HPV infection at any point in time. ► 610,000 incident cancers per annum are attributable to HPV infection globally. ► 80.6% of HPV associated cancers occur in less developed regions of the world. ► Cervix is the predominant HPV-associated cancer with 530,000 incident cases p.a. ► Genital warts are caused by HPV with an annual incidence of 0.1 to 0.2%. The worldwide prevalence of infection with human papillomavirus (HPV) in women without cervical abnormalities is 11–12% with higher rates in sub-Saharan Africa (24%), Eastern Europe (21%) and Latin America (16%). The two most prevalent types are HPV16 (3.2%) and HPV18 (1.4%). Prevalence increases in women with cervical pathology in proportion to the severity of the lesion reaching around 90% in women with grade 3 cervical intraepithelial neoplasia and invasive cancer. HPV infection has been identified as a definite human carcinogen for six types of cancer: cervix, penis, vulva, vagina, anus and oropharynx (including the base of the tongue and tonsils). Estimates of the incidence of these cancers for 2008 due to HPV infection have been calculated globally. Of the estimated 12.7 million cancers occurring in 2008, 610,000 (Population Attributable Fraction [PAF]=4.8%) could be attributed to HPV infection. The PAF varies substantially by geographic region and level of development, increasing to 6.9% in less developed regions of the world, 14.2% in sub-Saharan Africa and 15.5% in India, compared with 2.1% in more developed regions, 1.6% in Northern America and 1.2% in Australia/New Zealand. Cervical cancer, for which the PAF is estimated to be 100%, accounted for 530,000 (86.9%) of the HPV attributable cases with the other five cancer types accounting for the residual 80,000 cancers. Cervical cancer is the third most common female malignancy and shows a strong association with level of development, rates being at least four-fold higher in countries defined within the low ranking of the Human Development Index (HDI) compared with those in the very high category. Similar disparities are evident for 5-year survival—less than 20% in low HDI countries and more than 65% in very high countries. There are five-fold or greater differences in incidence between world regions. In those countries for which reliable temporal data are available, incidence rates appear to be consistently declining by approximately 2% per annum. There is, however, a lack of information from low HDI countries where screening is less likely to have been successfully implemented. Estimates of the projected incidence of cervical cancer in 2030, based solely on demographic factors, indicate a 2% increase in the global burden of cervical cancer, i.e., in balance with the current rate of decline. Due to the relative small numbers involved, it is difficult to discern temporal trends for the other cancers associated with HPV infection. Genital warts represent a sexually transmitted benign condition caused by HPV infection, especially HPV6 and HPV11. Reliable surveillance figures are difficult to obtain but data from developed countries indicate an annual incidence of 0.1 to 0.2% with a peak occurring at teenage and young adult ages. This article forms part of a special supplement entitled “Comprehensive Control of HPV Infections and Related Diseases” Vaccine Volume 30, Supplement 5, 2012.

Cervical cancer incidence remains high in several Baltic, central, and eastern European (BCEE) countries, mainly as a result of a historical absence of effective screening programmes. As a catalyst for action, we aimed to estimate the number of women who could be spared from cervical cancer across six countries in the region during the next 25 years, if effective screening interventions were introduced. In this population-based study, we applied age–period–cohort models with spline functions within a Bayesian framework to incidence data from six BCEE countries (Estonia, Latvia, Lithuania, Belarus, Bulgaria, and Russia) to develop projections of the future number of new cases of cervical cancer from 2017 to 2040 based on two future scenarios: continued absence of screening (scenario A) versus the introduction of effective screening from 2017 onwards (scenario B). The timespan of available data varied from 16 years in Bulgaria to 40 years in Estonia. Projected rates up to 2040 were obtained in scenario A by extrapolating cohort-specific trends, a marker of changing risk of human papillomavirus (HPV) infection, assuming a continued absence of effective screening in future years. Scenario B added the effect of gradual introduction of screening in each country, under the assumption period effects would be equivalent to the decreasing trend by calendar year seen in Denmark (our comparator country) since the progressive regional introduction of screening from the late 1960s. According to scenario A, projected incidence rates will continue to increase substantially in many BCEE countries. Very high age-standardised rates of cervical cancer are predicted in Lithuania, Latvia, Belarus, and Estonia (up to 88 cases per 100 000). According to scenario B, the beneficial effects of effective screening will increase progressively over time, leading to a 50–60% reduction of the projected incidence rates by around 2040, resulting in the prevention of cervical cancer in 1500 women in Estonia and more than 150 000 women in Russia. The immediate launch of effective screening programmes could prevent almost 180 000 new cervical cancer diagnoses in a 25-year period in the six BCEE countries studied. Based on our findings, there is a clear need to begin cervical screening in these six countries as soon as possible to reduce the high and increasing incidence of cervical cancer over the next decades. None.

Rwanda and Bhutan, 2 low- and middle-income countries, implemented primarily school-based national human papillomavirus (HPV) vaccination in 2011 (Rwanda) and 2010 (Bhutan). We estimated vaccination effectiveness through urine-based HPV prevalence surveys in schools in 2013-2014 and 2017. In Rwanda, 912 participants from baseline surveys and 1,087 from repeat surveys were included, and in Bhutan, 973 participants from baseline surveys and 909 from repeat surveys were included. The overall effectiveness against vaccine-targeted HPV types (i.e., HPV-6/11/16/18) was 78% (95% CI 51%-90%) in Rwanda, and 88% (6%-99%) in Bhutan and against other α-9 types was 58% (21-78) in Rwanda and 63% (27-82) in Bhutan. No effect against other HPV types was detectable. Prevalence of vaccine-targeted HPV types decreased significantly, as well as that of other α-9 types, suggesting cross-protection. These findings provide direct evidence from low- and middle-income countries of the marked effectiveness of high-coverage school-based, national HPV vaccination programs.