HUMAN PAPILLOMAVIRUS

Endemic malaria and helminth infections in sub-Saharan Africa can act as immunological modulators and impact responses to standard immunizations. We conducted a cohort study to measure the influence of malaria and helminth infections on the immunogenicity of the bivalent HPV-16/18 vaccine. We evaluated the association between malaria and helminth infections, and HPV-16/18 antibody responses among 298 Tanzanian females aged 10-25 years enrolled in a randomized controlled trial of the HPV-16/18 vaccine. Malaria parasitaemia was diagnosed by examination of blood smears, and helminth infections were diagnosed by examination of urine and stool samples, respectively. Geometric mean antibody titres (GMT) against HPV-16/18 antibodies were measured by enzyme-linked immunosorbent assay. Parasitic infections were common; one-third (30.4%) of participants had a helminth infection and 10.2% had malaria parasitaemia. Overall, the vaccine induced high HPV-16/18 GMTs, and there was no evidence of a...

BACKGROUNDThe addition of human papillomavirus (HPV) DNA testing to cytologic screening for cervical carcinoma is now being considered. The majority of women in screening cohorts who test positive for oncogenic types of HPV DNA have concurrent negative Pap tests. The absolute risk of a subsequent abnormal Pap test for these women is uncertain. Therefore, the proper counseling and clinical management of these women is also uncertain.The addition of human papillomavirus (HPV) DNA testing to cytologic screening for cervical carcinoma is now being considered. The majority of women in screening cohorts who test positive for oncogenic types of HPV DNA have concurrent negative Pap tests. The absolute risk of a subsequent abnormal Pap test for these women is uncertain. Therefore, the proper counseling and clinical management of these women is also uncertain.METHODSA subcohort of 2020 women with a negative Pap test who tested positive at enrollment for oncogenic HPV DNA types using the Hybrid Capture 2 Test were followed for 57 months at Kaiser Permanente (Portland, OR). Absolute risks of new abnormal cytologic interpretations were computed using Kaplan–Meier methods. Logistic regression models were used to evaluate determinants of a new abnormal Pap test.A subcohort of 2020 women with a negative Pap test who tested positive at enrollment for oncogenic HPV DNA types using the Hybrid Capture 2 Test were followed for 57 months at Kaiser Permanente (Portland, OR). Absolute risks of new abnormal cytologic interpretations were computed using Kaplan–Meier methods. Logistic regression models were used to evaluate determinants of a new abnormal Pap test.RESULTSThe cumulative incidence for a Pap test interpreted as atypical squamous cells or more severe (≥ ASC) was 16.8% (95% confidence interval [CI] = 15.0–18.6%), 6.4% (95% CI = 5.2–7.6%) for low-grade squamous intraepithelial lesions or more severe, and 2.2% (95% CI = 1.5–2.9%) for high-grade squamous intraepithelial lesions or more severe. By comparison, the cumulative incidence of greater than or equal to ASC among HPV-negative women was 4.2% (95% CI = 3.9–4.6%). The highest viral load (100 relative light units per the positive control or greater) was associated with a greater risk of an abnormal Pap test (odds ratio= 2.7, 95% CI = 1.7–4.1) than lower viral loads.The cumulative incidence for a Pap test interpreted as atypical squamous cells or more severe (≥ ASC) was 16.8% (95% confidence interval [CI] = 15.0–18.6%), 6.4% (95% CI = 5.2–7.6%) for low-grade squamous intraepithelial lesions or more severe, and 2.2% (95% CI = 1.5–2.9%) for high-grade squamous intraepithelial lesions or more severe. By comparison, the cumulative incidence of greater than or equal to ASC among HPV-negative women was 4.2% (95% CI = 3.9–4.6%). The highest viral load (100 relative light units per the positive control or greater) was associated with a greater risk of an abnormal Pap test (odds ratio= 2.7, 95% CI = 1.7–4.1) than lower viral loads.CONCLUSIONSThese results suggest that about 15% of women in annual screening programs who concurrently have a negative Pap test and a positive oncogenic HPV test will have a subsequent abnormal Pap test within 5 years. This risk estimate will be useful to the many clinicians and patients likely to be diagnosed with an HPV infection and negative cytology if HPV DNA is added to general screening. Cancer 2002;95:2145–51. Published 2002 by the American Cancer Society.DOI 10.1002/cncr.10927These results suggest that about 15% of women in annual screening programs who concurrently have a negative Pap test and a positive oncogenic HPV test will have a subsequent abnormal Pap test within 5 years. This risk estimate will be useful to the many clinicians and patients likely to be diagnosed with an HPV infection and negative cytology if HPV DNA is added to general screening. Cancer 2002;95:2145–51. Published 2002 by the American Cancer Society.DOI 10.1002/cncr.10927

To evaluate the association between human papillomavirus (HPV) and cervical cancer, we performed a population-based case-control study in Colombia and Spain, the former country having an incidence rate of cervical cancer about 8 times higher than the latter. It included 436 cases of histologically confirmed invasive cervical cancer and 387 randomly selected population controls. Information on demographic variables, sexual behaviour and other risk factors was obtained by interview. HPV-DNA was measured in cervical-swab specimens with 3 hybridization assays: ViraPap™, Southern hybridization (SH) and polymerase chain reaction (PCR). The presence of HPV-DNA and detection of types 16, 18, 31, 33 and 35 were strongly associated with cervical cancer in each country regardless of the assay used. For both countries combined the adjusted odds ratios and 95% confidence intervals were: ViraPap OR = 25.9 (10.0–66.7); SH OR = 6.8 (3.4–13.4); and PCR OR = 28.8 (15.7–52.6). HPV-16 was the most common type detected in both cases and controls. Our results indicate that there is a very strong association between HPV 16, 18, 31, 33 and 35 and invasive cervical cancer and that this association is probably causal. © 1992 Wiley-Liss, Inc.

The association between HIV infection and invasive cervical cancer that has been reported may reflect differential prevalence of human papillomavirus (HPV) infection or uncontrolled confounding. We conducted a case-control study in a West African population to assess the relationship between HIV infection and invasive cervical cancer, taking into account HPV infection and other potential risk factors for cervical cancer. Women with invasive cervical cancer (cases) or normal cervical cytology (controls) were recruited in a hospital-based case-control study in Abidjan, Côte d'Ivoire. Odds ratios and 95% confidence intervals (CI) were estimated in logistic regression analyses controlling for important cofactors. HIV infection was noted in 22/132 (16.7%) cases and 10/120 (8.3%) controls (p = 0.048). High-risk HPV infection was detected in cervical tumor samples from 89.4% of case-participants and in cervical cytology samples in 31.1% of control-participants. In logistic regression a...

This background paper analyses the events surrounding suspension of the human papillomavirus (HPV) vaccination recommendation by Japan’s Ministry of Health, Labour, and Welfare in response to public anxieties about a suspected adverse event following immunization. The paper explores how the issues in Japan have been perceived across the globe and the similarities and differences with HPV vaccine concerns in Australia, France, India, the United Kingdom, and the United Sates. The paper also presents possible options that Japanese stakeholders could take in the hope of resolving current concerns and uncertainty surrounding the HPV vaccine. Given the recognized importance of the human papillomavirus in causing multiple cancers, it is critical not to lose public trust in a vaccine that will only become more important in the future.

The expression of proliferating cell nuclear antigen (PCNA) was studied in human papillomavirus (HPV)-infected, benign and malignant lesions of the genital tract and larynx using immunocytochemical staining of formalin-fixed clinical specimens. We observed the induction of PCNA in squamous carcinomas and adenocarcinomas, as has been demonstrated with other malignancies. In addition, the differentiated keratinocytes of the upper spinous cells and granulocytes in condylomata acuminata and low-grade intraepithelial neoplasias showed a consistent induction of PCNA compared with the normal squamous epithelium, in which only some of the parabasal and basal cells were positive. This reactivation of PCNA synthesis correlated with the presence of high copy numbers of HPV DNA and was independent of the oncogenic risk potential of the infecting HPV genotype. We postulate that HPV gene products induce the expression of PCNA and other components of the host DNA replication machinery in different...

Cervical cancer is the second most common women cancer worldwide caused by human papillomavirus (HPV) infection. It is the main cause of women cancer deaths in developing countries including Thailand. Oncogenic proteins such as early (E) protein E6 and E7 of high risk (HR) HPV are associated with multistep process in cervical cancer carcinogenesis. Currently two commercially available prophylactic vaccines against HPV offer an opportunity to diminish the morbidity and mortality. However, they are not designated to control established HPV infection and related pre-invasive lesions and invasive cervical cancer patients. Powerful strategies in eradication and treatment are required for improving therapeutic HPV vaccines. This article provides basic knowledge and recent information related to HPV vaccines. The oncogenic types of HR-HPV focusing on prospective therapeutic vaccinations include (i) live vector-based vaccines (bacterial vector and viral vector vaccines), (ii) peptide/ prote...

HPV-induced diseases are extremely common and carry substantial morbidity and mortality. Existing methods of prevention and treatment are still inadequate. In this article, the use of Brassica oleracea (broccoli, cabbage, etc.), indole-3-carbinol (I3C), and diindolylmethane (DIM) to prevent and treat HPV-related conditions is discussed. Camellia sinensis (green tea) leaf catechins including epigallocatechin (EGC) and epigal-locatechin gallate (EGCG) and the approved botanical drug derived from them, sinecatechins, are used to illustrate an example of a very effective herbal treatment for genital warts. Other studies on herbal treatments for HPV-mediated diseases , including an immunostimulating formula including Echi-nacea purpurea; and a Chinese immune formula including As-tragalus membranaceus (astragalus), Platycodon grandiflorus (balloon flower), Angelica sinensis (dong quai), Wolfiporia cocos (hoelen), Ligustrum lucidum (privet), Glycyrrhiza ura-lensis (Asian licorice), and other herbs, and topical Periploca sepium (silk vine) are discussed.

Penile cancers are rare primary malignancies located on the glans, foreskin, or shaft of the penis, excluding the urethra. The vast majority of penile cancers are epithelial tumors representing histological subtypes of squamous cell carcinoma (SCC). Most penile SCCs are believed to develop through preinvasive lesions known as penile intraepithelial neoplasia and penile carcinoma in situ.

Penile cancers account for 0.1%–0.3% of all incident cancers (excluding non-melanoma skin cancers) in the United States and other developed countries and up to 1% of all cancers in some countries in sub-Saharan Africa. Annual incidence rates per 100,000 men (world standardized) are typically between 0.3 and 1.0 in developed countries, being 0.5 in the United States. During 2002–2011, SEER data showed rather stable penile cancer rates with no statistically significant changes in incidence or mortality.

Being rare in men younger than 40 years, penile cancers are typically diagnosed among men above age 60. The 5-year relative survival rate after penile cancer was 67% for all stages combined in US patients recorded in SEER registries during 2004–2010, with foreskin cancers having a more favorable prognosis than cancers at other penile sites.

The two most important risk factors for penile cancer are pathological phimosis and infection with high-risk types of human papillomaviruses (HPV), which are both preventable conditions. Non-surgical strategies to reduce the frequency of pathological phimosis need consideration, particularly because rates of newborn circumcision are declining in the United States and elsewhere. Increased awareness among doctors and parents about the importance of non-interference with the physiological foreskin separation process in young boys, and the promotion of safe-sex practices, possibly combined with preadolescent gender-neutral HPV vaccination programs, will likely reduce the frequencies of pathological phimosis and sexually acquired HPV infections and, eventually, reduce the burden of penile cancer at the population level.

Mathematics is a tool, but like any tool it can be used correctly or used incorrectly. I will explore how numbers are used and manipulated in the conversations about the health impact of circumcision. The difference between relative risk reduction and absolute risk reduction will be delineated. The derivation of number needed to treat and number needed to harm will be discussed, as well as how the number needed to treat for a urinary tract infection miraculously dropped from 195 to 4. The outcomes of three randomized clinical trials of circumcision’s impact on HIV incidence showed remarkably similar results: were the similarities too remarkable? Examples of the abuse of mathematics in the circumcision debate will be presented.

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