results: The association of systemic infections with malaria, brucellosis, cytomegalovirus and human immunodeficiency virus, dengue fever, influenza virus and of vaginal infection with bacterial vaginosis, with increased risk of miscarriage has been demonstrated. Q fever, adeno-asso- ciated virus, Bocavirus, Hepatitis C and Mycoplasma genitalium infections do not appear to affect pregnancy outcome. The effects of Chlamydia trachomatis, Toxoplasma gondii, human papillomavirus, herpes simplex virus, parvovirus B19, Hepatitis B and polyomavirus BK infections remain controversial, as some studies indicate increased miscarriage risk and others show no increased risk. The latest data on rubella and syphilis indicate increased antenatal screening worldwide and a decrease in the frequency of their reported associations with pregnancy failure. Though various pathogens have been associated with miscarriage, the mechanism(s) of infection-induced miscarriage are not yet fully elucidated.

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The role of infection in miscarriage

Around the world, infection is one of the most important causes of cancer. Almost one in every five malignancies can be attributed to infectious agents. Among infection-related neoplasms, cancers of the stomach, liver and cervix uteri detain the highest incidence figures, and are known to be largely attributable to Helicobacter pylori, hepatitis B and C viruses, and human papilloma virus, respectively. Other infectious organisms can also cause cancer; these include the Epstein-Barr virus (nasopharyngeal carcinoma, and different types of lymphoma), Human herpes virus-8 (Kaposi's Sarcoma), human T-cell leukemia virus type I (leukaemia, lymphoma), liver flukes (cholangiocarcinoma) and schistosomiasis (bladder cancer). Infection with human immunodeficiency virus, although strongly associated with an excess of cancer incidence at many cancer sites, is probably not carcinogenic per se, but acts mainly via immunodeficiency. The burden of infection-related cancers is still underestimated worldwide, due to the use of conservative population prevalence and risk ratio estimates. Furthermore, associations with new infectious agents remain yet to be explored.

Infections and cancer: established associations and new hypotheses.

Human papillomavirus (HPV) causes greater than 5% of cancers worldwide, including all cervical cancers and an alarmingly increasing proportion of oropharyngeal cancers (OPCs). Despite markedly reduced cervical cancer incidence in industrialized nations with organized screening programs, cervical cancer remains the second most common cause of death from cancer in women worldwide, as developing countries lack resources for universal, high-quality screening. In the United States, HPV-related OPC is only 1 of 5 cancers with a rising incidence since 1975 and now has taken over the cervix as the most common site of HPV-related cancer. Similar trends follow throughout North America and Europe. The need for early detection and prevention is paramount. Despite the common etiologic role of HPV in the development of cervical cancer and HPV-associated OPC, great disparity exists between incidence, screening modalities (or lack thereof), treatment, and prevention in these 2 very distinct cohorts. These differences in cervical cancer and HPV-associated OPC and their impact are discussed here. Cancer 2017;123:2219-2229. © 2017 American Cancer Society.

Human papillomavirus in cervical cancer and oropharyngeal cancer: One cause, two diseases

A pooled analysis of the safety of the human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine Cervarix (GlaxoSmithKline) was performed in a cohort of almost 30,000 girls and women aged > or =10 years, 16,142 who received at least one dose of the HPV-16/18 vaccine and 13,811 who received one of three controls [Al(OH)(3) or hepatitis A vaccine (720 or 360 EU)] Data are available for a total of 45,988 vaccine doses Solicited local and general symptoms were recorded for seven days after each dose Serious adverse events (SAEs), pregnancies, medically significant conditions (MSCs) and new onset of chronic diseases (NOCDs), including new onset of autoimmune diseases (NOADs), were proactively monitored Data were analyzed by vaccine group according to age (10-14, 15-25 and >25 years) and reporting period (months 0-7, months 7-12 and >month 12) Rates of solicited local and general symptoms were higher in the HPV-16/18 vaccine group than in the control groups However, compliance with the three-dose schedule was high and did not differ between groups (934% for HPV-16/18 vaccine group versus 925% for pooled controls) No clinically relevant differences were seen between the HPV-16/18 vaccine and pooled control groups in rates of SAEs (28% versus 31%), MSCs (194% versus 214%), NOCDs (17% in both groups) or NOADs (04% versus 03%) Similarly, no differences in pregnancy outcomes or rates of withdrawals due to AEs or SAEs were observed between groups In conclusion, analysis of this large database shows the HPV-16/18 AS04-adjuvanted cervical cancer vaccine to have a favorable safety profile in women of all ages

Safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine for cervical cancer prevention: a pooled analysis of 11 clinical trials.

This study assesses knowledge, attitudes, and behavioural intention towards human papillomavirus (HPV) infection and vaccination in a random sample of 1348 adolescents and young women aged 14–24 years in Italy. A self-administered anonymous questionnaire covered demographics; knowledge about HPV infection, cervical cancer, and HPV vaccine; the perceived risk for contracting HPV infection and/or for developing cervical cancer, the perceived benefits of a vaccination to prevent cervical cancer, and willingness to receive an HPV vaccine. Only 23.3% have heard that HPV is an infection of the genital mucosa and about cervical cancer. Those older, with at least one parent who is a health care professional, with personal, familiar, or friendly history of cervical cancer, and having underwent a health checkup in the last year with information about HPV vaccination were significantly more knowledgeable. Risk perception scores (range: 1–10) of contracting HPV infection and of developing cervical cancer were 5.8 and 6.5. Older age, not having a parent who is a health care professional, having had a personal, familiar, or friendly history of cervical cancer, and need of additional information were predictors of the perceived susceptibility of developing cervical cancer. The vast majority professed intent to receive an HPV vaccine and the significant predictors were having at least one parent who is a health care professional, a high perceived risk of contracting HPV infection and of developing cervical cancer, and a high belief towards the utility of a vaccination for preventing cervical cancer. Knowledge about HPV infection and cervical cancer should be improved with more attention to the benefit of HPV vaccination.

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Human papillomavirus and vaccination: knowledge, attitudes, and behavioural intention in adolescents and young women in Italy.

Cervical cancer, the most common cancer affecting women in developing countries, is caused by persistent infection with "high-risk" genotypes of human papillomaviruses (HPV). The most common oncogenic HPV genotypes are 16 and 18, causing approximately 70% of all cervical cancers. Types 6 and 11 do not contribute to the incidence of high-grade dysplasias (precancerous lesions) or cervical cancer, but do cause laryngeal papillomas and most genital warts. HPV is highly transmissible, with peak incidence soon after the onset of sexual activity. A quadrivalent (types 6, 11, 16 and 18) HPV vaccine has recently been licensed in several countries following the determination that it has an acceptable benefit/risk profile. In large phase III trials, the vaccine prevented 100% of moderate and severe precancerous cervical lesions associated with types 16 or 18 among women with no previous infection with these types. A bivalent (types 16 and 18) vaccine has also undergone extensive evaluation and been licensed in at least one country. Both vaccines are prepared from non-infectious, DNA-free virus-like particles produced by recombinant technology and combined with an adjuvant. With three doses administered, they induce high levels of serum antibodies in virtually all vaccinated individuals. In women who have no evidence of past or current infection with the HPV genotypes in the vaccine, both vaccines show > 90% protection against persistent HPV infection for up to 5 years after vaccination, which is the longest reported follow-up so far. Vaccinating at an age before females are exposed to HPV would have the greatest impact. Since HPV vaccines do not eliminate the risk of cervical cancer, cervical screening will still be required to minimize cancer incidence. Tiered pricing for HPV vaccines, innovative financing mechanisms and multidisciplinary partnerships will be essential in order for the vaccines to reach populations in greatest need.

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Human papillomavirus and HPV vaccines: a review.

Papilomavirus humanos y vacunas anti-PVH: revisión

Introduction Cervical cancer is estimated to affect approximately 500 000 women each year, of whom 80% live in developing countries. Virtually all cervical cancer cases result from genital infection with human papillomavirus (HPV). Well-organized programmes of regular gynaecological screening and treatment of precancerous lesions have been very effective in preventing squamous cervical cancer (the most common kind) but have had less impact on adenocarcinoma (1) and are difficult to implement in low-resource settings. In 2006, a quadrivalent vaccine was licensed in several countries, and a bivalent vaccine has recently been licensed in Australia. Countries will need to consider whether and how to use these new vaccines. This document provides an overview of key information on HPV and HPV vaccines for policy-makers. It is based on a longer document ("Human Papillomavirus and HPV vaccines: technical information for policy-makers and health professionals') that has been reviewed by an international group of experts, available online at: http://www.who.int/vaccinesdocuments/DocsPDF07/866.pdf. HPV and cancers Human papillomaviruses are DNA viruses that infect basal epithelial (skin or mucosal) cells. There is international consensus that "high-risk" genotypes, including genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 66, can lead to cervical cancer (2) and are associated with other mucosal anogenital and head and neck cancers. Infections with other genotypes, termed "low-risk," can cause benign or low-grade cervical tissue changes and genital warts (condyloma acuminata), which are growths on the cervix, vagina, vulva and anus in women and the penis, scrotum or anus in men. They also cause epithelial growths over the vocal cords of children and adults (juvenile respiratory papillomatosis or recurrent respiratory papillomatosis) that require surgical intervention. Most HPV infections of the cervix are asymptomatic and more than 90% of detected infections are cleared within 2 years. (3) The degree of protection and duration of immunity after natural infection are not known. Only 50-60% of women develop serum antibodies to HPV after natural infection. (4) Early HPV infections may be accompanied by mild changes in the epithelium that are detectable by screening using virological and/or cytological techniques, allowing early treatment. Cytological examination of cervical smears can detect abnormal growth of squamous cells called squamous intraepithelial lesions (SIL) of low or high grade, depending on how much of the cervical epithelium is affected and how abnormal the cells appear. Cervical intraepithelial neoplasia (CIN) is a term for abnormal cells in the cervix that are detected by histological examination of cervical biopsies; grades from 1 to 3 are used to describe the proportion of the thickness of the cervical epithelium composed of abnormal cells seen in the histology section. In CIN 3, abnormal cells span greater than 2/3s of the cervical epithelium. Similar gradings exist for vaginal (VAlN 1-3) and vulvar (VIN 1-3) lesions. As the viral infection persists, it integrates into the human DNA and can lead to cancer precursors: moderate or severe cervical intra-epithelial neoplasia (CIN 2, CIN 3 or adenocarcinoma in situ (MS), often grouped together as CIN 2/3 or MS). If these remain untreated, they have a high chance of leading to cancer. (5) The main burden of HPV-related disease is due to cervical cancer. HPV was estimated to cause 100% of the almost 260 000 deaths from cervical cancer worldwide in 2005 (http://www.who.int/healthinfo/statistics/ bodprojections2030/en/index.html). About 80% of cancer cases attributable to HPV were in developing countries (Table 1). The highest estimated incidence rates are in sub-Saharan Africa, Melanesia, Latin America and the Caribbean, south-central Asia and south-east Asia. In the most developed countries, the primary economic burden of HPV disease is related to the early detection and management of precancerous lesions. …

Human Papillomavirus and HPV Vaccines: A review/Virus Du Papillome Humain et Vaccins Anti-VPH: bilan/Papilomavirus Humanos Y Vacunas Anti-PVH: Revision

KL Goldenthal

Papers

Human papillomavirus and HPV vaccines: a review.

Papilomavirus humanos y vacunas anti-PVH: revisión

Human Papillomavirus and HPV Vaccines: A review/Virus Du Papillome Humain et Vaccins Anti-VPH: bilan/Papilomavirus Humanos Y Vacunas Anti-PVH: Revision