Strong evidence now supports the adoption of cervical cancer prevention strategies that explicitly focus on persistent infection with the causal agent, human papillomavirus (HPV). To inform an evidence-based transition to a new public health approach for cervical cancer screening, we summarize the natural history and cervical carcinogenicity of HPV and discuss the promise and uncertainties of currently available screening methods. New HPV infections acquired at any age are virtually always benign, but persistent infections with one of approximately 12 carcinogenic HPV types explain virtually all cases of cervical cancer. In the absence of an overtly persistent HPV infection, the risk of cervical cancer is extremely low. Thus, HPV test results predict the risk of cervical cancer and its precursors (cervical intraepithelial neoplasia grade 3) better and longer than cytological or colposcopic abnormalities, which are signs of HPV infection. The logical and inevitable move to HPV-based cervical cancer prevention strategies will require longer screening intervals that will disrupt current gynecologic and cytology laboratory practices built on frequent screening. A major challenge will be implementing programs that do not overtreat HPV-positive women who do not have obvious long-term persistence of HPV or treatable lesions at the time of initial evaluation. The greatest potential for reduction in cervical cancer rates from HPV screening is in low-resource regions that can implement infrequent rounds of low-cost HPV testing and treatment.
Cervical infections by approximately 15 cancer-associated (carcinogenic) human papillomavirus (HPV) genotypes cause virtually all cervical cancer and its immediate precursor lesions worldwide. Prophylactic vaccines against human papillomavirus (HPV) types HPV16 and HP18, which cause 70% of cervical cancer worldwide, hold great promise for reducing the burden of cervical cancer worldwide. However, current HPV vaccines prevent future infections and related cervical abnormalities and do not treat pre-existing HPV infections. In the U.S., HPV vaccine introduction should be considered in the context of a very successful cervical cancer screening program that has reduced the rates of cervical cancer by 75% or more. Thus, HPV vaccines will only prevent an incremental number of additional cervical cancers in the U.S. The introduction of HPV vaccines can also prevent other HPV-related sequelae, most importantly cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3), which precede the development of cervical cancer and require clinical follow-up and treatment. Examining data from 7 clinical centers in the U.S., the median age of CIN2/3 is typically between 25-30 years of age in 2007; if screen-detected CIN2/3 develops on average 5-10 years after the causal infection is acquired, HPV vaccination will only prevent a significant proportion of CIN2/3 if it is given to women before the age of 26 and more so if given to women 18 and younger. It is increasingly evident that prophylactic HPV vaccines will provide the greatest public health or population benefit only when delivered to adolescent women.
Human papillomavirus (HPV) is necessary for the development of cervical cancer. Cervical cancer is the second most common cancer in women worldwide but 80% occurs in developing countries, not countries with Pap screening programs. Pap screening programs in industrialized countries have reduced the incidence of cervical cancer to 4–8/100,000 women. HPV vaccines may be a promising strategy for cervical cancer in women without access to screening programs. In industrialized countries, the benefit of HPV vaccines focuses on individual abnormal Pap test reduction not cancer prevention.
The focus of this review is to cover the side effects of Gardasil in perspective with the limited population benefit cervical cancer reduction in countries with organized Pap screening programs. In addition, information about Gardasil benefits, risks and unknowns for individual patient decision making for vaccination is presented.
Gardasil offers protection against CIN 2+ lesions caused by HPV 16/18 and against genital warts caused by HPV 6/11 for at least 5 years. Combining Gardasil with repeated cytology screenings may reduce the proportion of abnormal cytology screens and hence reduce the associated morbidity with the subsequent colposcopies and excisional procedures.
Adverse effects; Cervical cancer; Duration of efficacy; HPV vaccine immunology; Gardasil
Pap screening, an effective method for cervical cancer prevention, is now supported by molecular human papillomavirus (HPV) testing. Recently commercialised preventive vaccines also provide new tools for the primary prevention of cervical cancer. To determine appropriate prevention strategies, the Health General Direction, Lombardy Region, funded a project that aims to characterize and monitor HPV infections and related cervical diseases in high-risk women.
VALHIDATE is a 5-year multicentre open prospective cohort study. It will recruit 7000 consenting women aged 13–65 years to provide information about the local biomolecular epidemiology of HPV infection and cervical diseases in high-risk women recruited from nine clinical centres and one faith-based organisation. The study will estimate the overall and type-specific prevalence of HPV infection and cervical abnormalities. It also aims to compare standard Pap screening with biomolecular screening, and to assist in the design of targeted regional prevention programs directed specifically at high-risk groups. Three groups of high-risk women: 1000 HIV-infected women (aged 26–65 years), 1000 recent migrant women (aged 26–65 years) and 3000 young women (aged 13–26 years) and 1 control group: 2000 women (aged 26–45 years) attending a spontaneous screening program, will be recruited. Sample sizes will be revised after the first year. Adult participants will undergo conventional cervical cytology, HPV DNA screening and genotyping. Paediatric participants will undergo HPV DNA testing and genotyping of urine samples. HPV DNA, cytological abnormalities and HPV types will be analysed according to demographic, epidemiological, behavioural, and clinical data collected in an electronic case report form. Overall and stratified prevalences will be estimated to analyse the associations between HPV infection and selected characteristics. Logistic regression models will be used to estimate crude and adjusted odds ratios. Cox proportional hazard models will be used to estimate hazard ratios over time and between groups.
Discussion/main expected results
This study will provide substantial insight into HPV infections and related cervical diseases in high-risk groups and will help determine appropriate regional cervical cancer prevention strategies.
Cervical cancer; Prevention; HPV; Epidemiology; Cytology screening; Molecular screening
Phase III trials have demonstrated the efficacy of human papillomavirus (HPV) vaccines in preventing transient and persistent high-risk (hr) HPV infection and precancerous lesions. A mathematical model of HPV type 16 infection and progression to cervical cancer, parameterised to represent the infection in Finland, was used to explore the optimal age at vaccination and pattern of vaccine introduction. In the long term, the annual proportion of cervical cancer cases prevented is much higher when early adolescents are targeted. Vaccinating against hr HPV generates greater long-term benefits if vaccine is delivered before the age at first sexual intercourse. However, vaccinating 12 year olds delays the predicted decrease in cervical cancer, compared to vaccinating older adolescents or young adults. Vaccinating males as well as females has more impact on the proportion of cases prevented when vaccinating at younger ages. Implementing catch-up vaccination at the start of a vaccination programme would increase the speed with which a decrease in HPV and cervical cancer incidence is observed.
HPV; vaccination; modelling
Over the past several decades, invasive cervical cancer (ICC) incidence in the United States has declined dramatically. Much of this decline has been attributed to widespread use of cytology screening followed by treatment of precancerous lesions. Despite available technologies to prevent ICC and screening programs targeting high-risk women, certain populations in the United States experience disproportionately high rates of ICC (e.g., racial/ethnic minorities and rural women). Limited access to and use of screening/follow-up services underlie this disparity. The licensure of the human papillomavirus (HPV) vaccine in 2006 introduced an additional method of ICC prevention. Unfortunately, dissemination of the vaccine to age-eligible females has been lower than expected (32% have received all 3 recommended doses). Decreasing the burden of HPV infection and HPV-related diseases in the United States will require greater dissemination of the HPV vaccine to adolescents and young adults, along with successful implementation of revised ICC screening guidelines that incorporate HPV and cytology cotesting. While a future without ICC is possible, we will need a comprehensive national health care program and innovative approaches to reduce ICC burden and disparities.
Human papillomavirus (HPV) infection is a major cause of cervical cancer and its precancerous diseases. Cervical cancer is the second deadliest cancer killer among women worldwide. Moreover, HPV is also known to be a causative agent of oral, pharyngeal, anal and genital cancer. Recent application of HPV structural protein (L1)-targeted prophylactic vaccines (Gardasil® and Cervarix®) is expected to reduce the incidence of HPV infection and cervical cancer, and possibly other HPV-associated cancers. However, the benefit of the prophylactic vaccines for treating HPV-infected patients is unlikely, underscoring the importance of developing therapeutic vaccines against HPV infection. In this regard, numerous types of therapeutic vaccine approaches targeting the HPV regulatory proteins, E6 and E7, have been tested for their efficacy in animals and clinically. In this communication, we review HPV vaccine types, in particular DNA vaccines, their designs and delivery by electroporation and their immunologic and antitumor efficacy in animals and humans, along with the basics of HPV and its pathogenesis.
Cervical cancer; Cervical intraepithelial neoplasia; DNA vaccines; Electroporation; Human papillomavirus
Disparities in cervical cancer incidence and mortality rates exist among women of African ancestry (African-American, African-Caribbean and African). Persistent cervical infection with Human papillomavirus (HPV) is associated with cervical dysplasia and if untreated, could potentially progress to invasive cervical cancer. Very few studies have been conducted to examine the true prevalence of HPV infection in this population. Comparisons of cervical HPV infection and the type-specific distribution of HPV were performed between cancer-free Caribbean and US women.
The Caribbean population consisted of 212 women from Tobago and 99 women from Jamaica. The US population tested, consisted of 82 women from Pittsburgh. The majority of the US subjects was Caucasian, 74% (61/82) while 12% (10/82) and 13% (11/82) were African-American or other ethnic groups, respectively. The age-adjusted prevalence of any HPV infection among women from Tobago was 35%, while for Jamaica, it was 81% (p < 0.0001). The age-adjusted prevalence of HPV infection for Caribbean subjects was not statistically significantly different from the US (any HPV: 47% vs. 39%, p > 0.1; high-risk HPVs: 27% vs. 25%, p > 0.1); no difference was observed between US-Blacks and Jamaicans (any HPV: 92% vs. 81%, p > 0.1; high-risk HPV: 50% vs. 53%, p > 0.1). However, US-Whites had a lower age-adjusted prevalence of HPV infections compared to Jamaican subjects (any HPV: 29% vs. 81%, p < 0.0001; high-risk HPV: 20% vs. 53%, p < 0.001). Subjects from Jamaica, Tobago, and US-Blacks had a higher proportion of high-risk HPV infections (Tobago: 20%, Jamaica: 58%, US-Blacks: 40%) compared to US-Whites (15%). Similar observations were made for the presence of infections with multiple high-risk HPV types (Tobago: 12%, Jamaica: 43%, US-Blacks: 30%, US-Whites: 8%). Although we observed similar prevalence of HPV16 infections among Caribbean and US-White women, there was a distinct distribution of high-risk HPV types when comparisons were made between the ethnic groups.
The higher prevalence of cervical HPV infections and multiple high-risk infections in Caribbean and US-Black women may contribute to the high incidence and prevalence of cervical cancer in these populations. Evaluation of a larger sample size is currently ongoing to confirm the distinct distribution of HPV types between ethnic groups.
There is a high incidence of cervical cancer in South African women. No large studies to assess human papillomavirus virus (HPV) infection or HPV type 16 (HPV-16) exposure have occurred in the region, a requirement for policy making with regards to HPV screening and the introduction of vaccines. Control women (n = 1,003) enrolled in a case control study of hormonal contraceptives and cervical cancer were tested for 27 cervical HPV types by reverse line blot analysis. The seroprevalence of HPV-16 immunoglobulin G (IgG) and IgA antibodies was assessed by a virus-like particle-based enzyme-linked immunoassay of 908 and 904 control women, respectively, and of 474 women with cervical cancer. The cervical HPV prevalence was 26.1%. The HPV-16 IgG seroprevalence was 44.4% and the HPV-16 IgA seroprevalence was 28.7% in control women, and these levels were significantly higher (61.8% and 52.7%, respectively) for women with cervical cancer (odds ratio [OR], 2.1 and 2.8, respectively). The cervical HPV prevalence showed an association with cervical disease, and the HPV-16 IgG prevalence decreased while the HPV-16 IgA prevalence increased with increasing age (P < 0.05). The prevalence of oncogenic HPV types (including HPV-16) decreased with age, whereas nononcogenic HPV types showed limited association with age. Multivariate analysis revealed cervical HPV infection to be associated with herpes simplex virus type 2 infection (OR, 1.7) and increasing years of education (OR, 1.9). HPV-16 IgG antibodies were inversely associated with current smoking status (OR, 0.6), and the presence of HPV-16 IgA antibodies was inversely associated with the use of alcohol (OR, 2.1) and inversely associated with the use of oral contraceptives (OR, 0.6). High levels of exposure to HPV, and particularly HPV-16, were evident in this population. The apparent increase of serum HPV-16 IgA with increasing age requires further investigation.
Cervical cancer is the second largest cause of cancer deaths in women worldwide. It is now evident that persistent infection with high-risk human papillomavirus (HPV) is necessary for the development and maintenance of cervical cancer. Thus, effective vaccination against HPV represents an opportunity to restrain cervical cancer and other important cancers. The FDA recently approved the HPV vaccine Gardasil for the preventive control of HPV, using HPV virus-like particles (VLP) to generate neutralizing antibodies against major capsid protein, L1. However, prophylactic HPV vaccines do not have therapeutic effects against pre-existing HPV infections and HPV-associated lesions. Furthermore, due to the considerable burden of HPV infections worldwide, it would take decades for preventive vaccines to affect the prevalence of cervical cancer. Thus, in order to speed up the control of cervical cancer and treat current infections, the continued development of therapeutic vaccines against HPV is critical. Therapeutic HPV vaccines can potentially eliminate pre-existing lesions and malignant tumors by generating cellular immunity against HPV-infected cells that express early viral proteins such as E6 and E7.
This review discusses the future directions of therapeutic HPV vaccine approaches for the treatment of established HPV-associated malignancies, with emphasis on current progress of HPV vaccine clinical trials.
Relevant literature is discussed.
Though their development has been challenging, many therapeutic HPV vaccines have been shown to induce HPV-specific antitumor immune responses in preclinical animal models and several promising strategies have been applied in clinical trials. With continued progress in the field of vaccine development, HPV therapeutic vaccines may provide a potentially promising approach for the control of lethal HPV-associated malignancies.
clinical trials; HPV; human papillomavirus; therapeutic; vaccines
Human papillomavirus (HPV)-related cancers are a major worldwide public health concern. Virtually all cervical cancer is HPV-related, with 70% caused by HPV16 and -18. Variable proportions of certain non-cervical cancers (e.g., anal, vulvar, oropharyngeal) are HPV-related; over 90% of the HPV-related ones are related to HPV16, -18. The HPV-related cancers are dominated by cervical cancer in the developing world, where cervical cancer screening is limited. In this setting, widespread uptake of current HPV vaccines by adolescent girls could reduce this cancer's incidence and mortality by approximately two-thirds, with cost-effective screening programs of adult women having the potential to reduce mortality more rapidly. In the industrialized world, non-cervical HPV-related cancers, especially oropharyngeal, are rapidly increasing, and now rival the incidence of cervical cancer, whose rates continue to decline thanks to established cervical screening programs. Therefore, reducing HPV-associated non-cervical cancers with HPV vaccination has greater importance in the industrialized world, especially since there are no approved screening programs for these cancers. Preventing the substantial number of non-cervical HPV cancers in men will require either “herd” immunity through high vaccination rates in females or male vaccination. Current HPV vaccination can complement cervical screening in protecting against cervical cancer and may permit the safe reduction of screening intensity in industrialized countries. Second-generation HPV vaccines (active against a broader array of cervical cancer–related HPV types) could prevent an even higher proportion of cervical precancer and cancer and might permit further reductions in screening intensity.
Cervical cancer is one of the most common cancers in women worldwide. Persistent infection with human papillomavirus (HPV) is considered to be the etiological factor for cervical cancer. Therefore, an effective vaccine against HPV infections may lead to the control of cervical cancer. An ideal HPV vaccine should aim to generate both humoral immune response to prevent new infections as well as cell-mediated immunity to eliminate established infection or HPV-related disease. In the current study, we have generated a potential preventive and therapeutic HPV DNA vaccine using human calreticulin (CRT) linked to HPV16 early proteins, E6 and E7 and the late protein L2 (hCRTE6E7L2). We found that vaccination with hCRTE6E7L2 DNA vaccine induced a potent E6/E7-specific CD8+ T cell immune response, resulting in a significant therapeutic effect against E6/E7 expressing tumor cells. In addition, vaccination with hCRTE6E7L2 DNA generated significant L2-specific neutralizing antibody responses, protecting against pseudovirion infection. Thus, the hCRTE6E7L2 DNA vaccines are capable of generating potent preventive and therapeutic effects in vaccinated mice. Our data has significant clinical implications.
HPV; DNA vaccine; E6; E7; L2
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.
attitudes; behavioural intention; cervical cancer; human papillomavirus; Italy
Cervical cancer is the second largest cause of cancer-related death in women worldwide, and it occurs following persistent infection, sometimes for decades, with a specific subset of human papillomavirus (HPV) types; the approximately 13 oncogenic subtypes. Prophylactic vaccines against HPV infections hold promise for cost-effective reductions in the incidence of cervical cancer, but this may not be enough. Two prophylactic HPV vaccines are presently available and both contain L1 virus-like particles (VLPs) derived from the HPV subtypes most frequently associated with cervical cancer, HPV-16 and -18. Since the L1-VLP vaccines can only effectively prevent infection by the specific HPV subtype against which the vaccine was developed, cervical cancers caused by high-risk HPV subtypes other than HPV-16 and -18 may still occur in recipients of the current HPV vaccines. Furthermore, HPV vaccination coverage for adolescents is insufficient in most countries and therefore even HPV-16 and -18 infections are unlikely to be fully eradicated using the existing strategies. The development of HPV therapeutic vaccines remains essential. Many therapeutic vaccines aimed at clearing HPV-related cervical lesions have been developed and tested in patients with HPV16-positive cervical intraepithelial lesions (CIN) or cervical cancers. To date, definitive clinical efficacy and appropriate immunological responses have never been demonstrated for cervical neoplasia although promising results have been reported in patients with vulvar intraepithelial neoplasia. Here we discuss shortcomings of previous HPV therapeutic vaccine candidates and propose a novel vaccination strategy that leverages newly gained knowledge about mucosal immunity and the induction of mucosal immune responses.
HPV therapeutic vaccine; mucosal vaccination; cervical mucosal immune system; E7-expressing lactobacillusbases vaccine.
Persistent cervical infections by approximately 15 carcinogenic genotypes of human papillomavirus (HPV) cause virtually all cases of cervical cancer and its immediate precancerous precursor, cervical intraepithelial neoplasia grade 3 or carcinoma in situ. As is shown in a meta-analysis by Koshiol et al. (Am J Epidemiol 2008;168:123–137), detection of carcinogenic HPV viral persistence could be used to identify women at the greatest risk of cervical precancer. Specifically, women who have carcinogenic HPV infection that persists for at least 1 year versus those whose infections clear are at significantly elevated risk of having or developing cervical precancer. However, before detection of HPV persistence can be used in cervical cancer screening, several considerations need to be addressed: 1) validation and Food and Drug Administration approval of a reliable HPV genotyping test, 2) rational clinical algorithms based on risk of precancer and cancer for the clinical management of HPV persistence, 3) clinician and patient acceptability of monitoring of HPV infections (including not responding excessively to the first positive HPV test and waiting 1–2 years for infections to either persist or resolve), and 4) patient compliance with recommended follow-up. Investigators will need to address these and other key issues in order to realize the potential utility of HPV viral monitoring for improving the accuracy of cervical cancer screening.
human papillomavirus 16; human papillomavirus 18; longitudinal studies; papillomavirus infections; uterine cervical neoplasms
Cervical cancer is the second most common cancer of women worldwide and is the first cancer shown to be entirely induced by a virus, the human papillomavirus (HPV, major oncogenic genotypes HPV-16 and -18). Two recently developed prophylactic cervical cancer vaccines, using virus-like particles (VLP) technology, have the potential to prevent a large proportion of cervical cancer associated with HPV infection and to ensure long-term protection. However, prophylactic HPV vaccines do not have therapeutic effects against pre-existing HPV infections and do not prevent their progression to HPV-associated malignancy. In animal models, therapeutic vaccines for persisting HPV infection can eliminate transplantable tumors expressing HPV antigens, but are of limited efficacy in inducing rejection of skin grafts expressing the same antigens. In humans, clinical trials have reported successful immunotherapy of HPV lesions, providing hope and further interest. This review discusses possible new approaches to immunotherapy for HPV associated cancer, based on recent advances in our knowledge of the immunobiology of HPV infection, of epithelial immunology and of immunoregulation, with a brief overview on previous and current HPV vaccine clinical trials.
HPV; vaccine; virus-like particles; immunotherapy
Human Papillomavirus (HPV) is responsible for 99.7% of cervical cancer cases and an estimated 5% of all cancers worldwide. The largest burden from HPV-associated cervical cancers is in developing nations where effective cervical cancer screening programs are non-existent. Even in developed nations, diagnosis and treatment of cervical precancers continue to be large economic burdens. Prophylactic vaccination against HPV is an ideal method for the prevention of cervical cancer and other HPV associated diseases. Safe and effective virus-like-particle-derived prophylactic vaccines are available to most nations. The high cost of the current vaccines makes it out of reach for most developing nations. Since millions of women are already infected with HPV and have serious disease, therapeutic HPV vaccines are being developed to treat these women. The article presents the natural history, oncogenesis, and host immune interactions of HPV and associated diseases. The article also discusses the safety and efficacy of commercially available prophylactic vaccines against HPV, as well as novel prophylactic and therapeutic vaccine delivery strategies in early clinical development.
Cervical cancer remains to be one of the leading malignancies among Filipino women. High-risk human papillomavirus (HPV) types, such as 16 and 18, are consistently identified in Filipino women with cervical cancer. Factors identified to increase the likelihood of HPV infection and subsequent development of cervical cancer include young age at first intercourse, low socioeconomic status, high parity, smoking, use of oral contraception and risky sexual behaviors. Cancer screening programs presently available in the Philippines include Pap smears, single visit approach utilizing visual inspection with acetic acid followed by cryotherapy, as well as colposcopy. However, the uptake of screening remains low and is further compounded by the lack of basic knowledge women have regarding screening as an opportunity for prevention of cervical cancer. Prophylactic HPV vaccination of both quadrivalent and bivalent vaccines has already been approved in the Philippines and is gaining popularity among the Filipinos. However, there has been no national or government vaccination policy implemented as of yet. The standard of treatment of cervical cancer is radiotherapy concurrent with chemotherapy. Current researches are directed towards improving availability of both preventive and curative measures of cervical cancer management.
Cervical cancer; Epidemiology; Screening; Human papillomavirus vaccines
Certain high-risk (HR) human papillomavirus (HPV) types are a necessary cause for the development of cervical disorders. Women with persistent HR HPV infections have an increased risk of developing high-grade cervical lesions, compared with those who have no or low-risk HPV infections. Therefore, implementation of HPV detection into cervical screening programs might identify women at risk of cervical cancer. Several HPV detection methods with different sensitivities and specificities are available. Recently, a new PCR-based technique, the Roche AMPLICOR HPV Test, was developed. This test recognizes a group of 13 HR HPV types simultaneously. This study was undertaken to validate and compare HPV detection in 573 cervical scrape specimens by the AMPLICOR HPV Test and the INNO-LiPA HPV detection/genotyping assay (SPF10-LiPA system version 1). Human β-globin was not detected in nine specimens, which were therefore excluded from the comparison. Eleven scrape specimens containing HPV type 53 or 66 were also excluded from the comparison because these (probably) HR HPV types cannot be detected by the AMPLICOR HPV Test. The results of HPV detection by the Roche AMPLICOR HPV Test were confirmed by INNO-LiPA HPV detection/genotyping assay in 539/553 cases, showing an absolute agreement of 97.5% with a Cohen's kappa of 0.9327, indicating almost complete similarity of the two tests. Like the INNO-LiPA HPV detection/genotyping assay, the AMPLICOR HPV Test was sensitive, specific, feasible, and easy to handle. The value of the Roche AMPLICOR HPV Test with a broad-spectrum HR HPV detection has to be determined in prospective clinical studies.
Background. HPV vaccination may prevent thousands of cases of cervical cancer. We aimed to evaluate the understanding and acceptance of the HPV vaccine among adolescents. Methods. A questionnaire was distributed to adolescents at health clinics affiliated with a large urban hospital system to determine knowledge pertaining to sexually transmitted diseases and acceptance of the HPV vaccine. Results. 223 adolescents completed the survey. 28% were male, and 70% were female. The mean age for respondents was 16 years old. Adolescents who had received the HPV vaccine were more likely to be female and to have heard of cervical cancer and Pap testing. Of the 143 adolescents who had not yet been vaccinated, only 4% believed that they were at risk of HPV infection and 52% were willing to be vaccinated. Conclusions. Surveyed adolescents demonstrated a marginal willingness to receive the HPV vaccine and a lack of awareness of personal risk for acquiring HPV.
Human papillomavirus (HPV), a sexually transmitted infection and
the etiologic cause of genital warts and cervical cancer, is
highly prevalent in sexually active men and women. Although
cervical screening procedures have significantly reduced the
disease burden associated with HPV infection, they are expensive
and abnormal results cause significant emotional distress.
Therefore, prevention may be an effective strategy for reducing
the economic, psychosocial, and disease burden of HPV infection.
Multivalent vaccines are now in clinical development. A bivalent
vaccine that protects against HPV 16 and 18, and a quadrivalent
vaccine which protects against HPV types 6, 11, 16, and 18, have
been shown to significantly reduce the occurrence of incident and
persistent HPV infections in phase 2 clinical trials; phase 3
trials are currently underway. HPV vaccines will be most effective
when administered prior to initiation of sexual activity, and
vaccination campaigns should aggressively target preadolescent and
Genital human papillomavirus (HPV) infection is one of the most commonly diagnosed sexually transmitted infections world-wide. Over the last two decades, research has established a strong causal link between specific types of HPV infection and cancer, particularly cervical, anal, vulvar/vaginal, penile, and oropharyngeal cancer. Limited epidemiological studies of anogenital HPV infection have been conducted in Hispanic populations (including Puerto Rico), and population-based incidence and prevalence estimates of HPV infection among Hispanics are limited. Studies that evaluate knowledge and awareness of HPV among men are also scarce. With the world-wide introduction of two new prophylactic vaccines against high-risk HPVs causing cervical cancer, and the recent FDA approval of the quadrivalent vaccine in preventing genital warts in men, there is an urgency to determine the burden of HPV in Hispanic populations before vaccine programs are implemented on a widespread basis. Knowledge and acceptability of the vaccine prior to implementation of these programs are also necessary to allow a targeted assessment. This review article summarizes existing research on HPV infection and HPV-related morbidities in men, with a particular emphasis on Hispanic men in the United States and Puerto Rico. Three major areas are discussed: (1) genital warts, (2) HPV and related cancers and (3) biobehavioral and psychosocial factors related to HPV infection and vaccination. Specific recommendations for advancing HPV research and knowledge among Hispanic populations also are suggested.
HPV infection; Men; Hispanics; Puerto Rico; Anal cancer; Penile cancer
There have been no published studies of carcinogenic human papillomavirus (HPV)--the necessary cause of cervical cancer--in Haiti, a nation that has one of the greatest burdens of cervical cancer globally.
Characterize prevalence of carcinogenic HPV and the prevalence of individual carcinogenic HPV genotypes in women with cervical precancer or cancer, cervical intraepithelial neoplasia grade 2 (CIN2) or more severe (CIN2+).
Women (n=9,769; aged 25-60 years) were screened for carcinogenic HPV by Hybrid Capture 2 (HC2; Qiagen, Gaithersburg, MD). Carcinogenic HPV positives underwent colposcopy and visible lesions were biopsied. A subset of carcinogenic HPV positives was tested for individual HPV genotypes using a GP5+/6+ assay.
The prevalence of carcinogenic HPV was 19.0% (95% confidence interval: 18.4%-19.9%) and decreased with increasing age (ptrend < 0.001). Women with 3 or more sexual partners and who started sex before the age of 18 years had twice the age-adjusted prevalence of carcinogenic HPV of women with one partner and who started sex after the age of 21 (24.3% vs. 12.9%, respectively). HPV16 and HPV35 were the most common HPV genotypes detected in CIN2+ and more common in women with CIN2+ than those without CIN2+. HPV16 and/or HPV18 were detected in 21.0% of CIN2 (n = 42), 46.2% of CIN3 (n = 52), and 80% of cancers (n = 5).
The prevalence of carcinogenic HPV in Haiti was much greater than the prevalence in other Latin American countries. High carcinogenic HPV prevalence and a lack of cervical cancer screening may explain the high burden of cervical cancer in Haiti.
Cervical carcinomas are almost universally associated with high-risk human papillomavirus (HPV) infections, and are a leading cause of cancer death in women worldwide. HPV oncoproteins contribute to cancer initiation and progression and their expression is necessary for the maintenance of the transformed state. The fact that the initiating oncogenic insult, infection with a high-risk HPV and viral oncoprotein expression, is common to almost all cervical cancers offers unique opportunities for prevention, early detection, and therapy. The potential for prevention has been realized by introduction of prophylactic vaccines that are to prevent transmission of specific high-risk HPVs. Given, however, that these vaccines have no therapeutic efficacy and HPV-associated cervical cancers arise years if not decades after the initial infection, it has been estimated that there will be no measurable decline of HPV-associated tumors before 2040. Cervical cancer alone will be diagnosed in more than 375,000 US women between now and 2040. Other HPV-associated anogenital and head and neck cancers are predicted to afflict another 700,000 men and women over this time period. Hence, therapeutic efforts to combat high-risk HPV-associated disease remain of critical importance.
Persistent infection with carcinogenic human papillomavirus (HPV) is linked to high-grade lesions and cervical cancer. To better understand the natural history of HPV, we sought to determine the rates of incident and cleared carcinogenic HPV infection, by age, among women aged 15–49 years and to explore risk factors for incident infection.
Women enrolled in an earlier HPV prevalence survey (500 of 800 who were HPV-negative and all 121 who were HPV-positive) were invited to participate in follow-up HPV testing at their periodic health examination one year later. A cervical soft-brush specimen for HPV testing and a smear for cytologic examination were obtained, and participants completed a questionnaire on their demographic characteristics and sexual history.
Two hundred and fifty-three (50.6%) previously HPV-negative women and 54 (44.6%) previously HPV-positive women were retested. The mean interval between visits was 14.0 (standard deviation 2.0, median 13.5, range 9.0–21.3) months. Incident HPV infection occurred in 11.1% (28/253) of the women overall, with the highest rate, 25.0% (6/24), in the 15–19-year age group. In the univariate analyses, risk factors for incident HPV were the median number of sexual partners in the past year (≤ 1 v. ≥ 2: odds ratio [OR] 8.2, 95% confidence interval [CI] 3.0–22.2; p < 0.001) and the median number of sexual partners over a lifetime (> 3 v. ≤ 3: OR 3.0, 95% CI 1.2–7.2; p = 0.014). In multivariate logistic regression modelling adjusted for age, median number of sexual partners in the past year, median number of sexual partners over a lifetime, marital status, current smoking and current use of oral contraceptives, only the median number of sexual partners in the past year remained significantly associated with incidence (OR 6.2, 95% CI 1.6–24.5; p = 0.009). Of the previously HPV-positive women, 51.9% (28/54) had cleared the infection.
Incident infection with carcinogenic HPV was highest in women aged 15–19 years, and risk factors were consistent with a sexually transmitted infection. A large proportion of the women who were HPV-positive appeared to have cleared the infection after one year.