Cause Of Invasive Cervical Cancer Research Articles

Associations of clinical and modifiable behavioral risk factors with the histological progression of squamous intraepithelial lesions.

Cervical cancer is the third most common cancer in women worldwide. Human papillomavirus (HPV) has been established as a cause of invasive cervical cancer. However, HPV is predominantly transient and only a minority of cases persist and progress clinically. Certain epidemiological factors have been suggested to increase the risk of HPV persistence and progression. In the present study, 893 women were investigated, with an age range from 25 to 60 years old. PAP smears and colposcopy were used for assessment. Of these women, 108 were diagnosed with squamous intraepithelial lesions (SILs) and were further divided into high-grade SIL (HSIL) and low-grade SIL (LSIL). The dietary habits, sleep patterns and gynecological histories of these participants were studied, and it was found that the probability of having <3 meals a day [odds ratio (OR), 4.35; 95% confidence interval (CI), 1.73-10.95], having an unbalanced diet (OR, 3.90; 95% CI, 1.44-10.55), breakfast skipping (OR, 6.32; 95% CI, 2.40-16.61) and disrupted sleep (OR, 4.42; 95% CI, 1.79-10.93) was significantly higher in the HSIL group compared with the probability in the LSIL group. In addition, participants who had pregnancies prior to the age of 20 were 2.85 times more likely to have more advanced disease (OR, 2.85; 95% CI, 1.22-6.71). Cervical erosion was higher in the HSIL group compared with that in the LSIL group (OR, 3.31; 95% CI, 1.36-6.96). The present study highlights the protective effects of meal numbers, nutritious diet and sleep hygiene against HPV and the progression of SIL.

HPV genotyping by L1 amplicon sequencing of archived invasive cervical cancer samples: a pilot study

BackgroundHuman papillomavirus (HPV) is the primary cause of invasive cervical cancer (ICC). The prevalence of various HPV genotypes, ranging from oncogenically low- to high-risk, may be influenced by geographic and demographic factors, which could have critical implications for the screening and prevention of HPV infection and ICC incidence. However, many technical factors may influence the identification of high-risk genotypes associated with ICC in different populations.MethodsWe used high-throughput sequencing of a single amplicon within the HPV L1 gene to assess the influence of patient age, race/ethnicity, histological subtype, sample type, collection date, experimental factors, and computational parameters on the prevalence of HPV genotypes detected in archived DNA (n = 34), frozen tissue (n = 44), and formalin-fixed paraffin-embedded (FFPE) tissue (n = 57) samples collected in the Los Angeles metropolitan area.ResultsWe found that the percentage of off-target human reads and the concentration of DNA amplified from each sample varied by HPV genotype and by archive type. After accounting for the percentage of human reads and excluding samples with especially low levels of amplified DNA, the HPV prevalence was 95% across all ICC samples: HPV16 was the most common genotype (in 56% of all ICC samples), followed by HPV18 (in 21%). Depending upon the genotyping parameters, the prevalence of HPV58 varied up to twofold in our cohort. In archived DNA and frozen tissue samples, we detected previously established differences in HPV16 and HPV18 frequencies based on histological subtype, but we could not reproduce those findings using our FFPE samples.ConclusionsIn this pilot study, we demonstrate that sample collection, preparation, and analysis methods can influence the detection of certain HPV genotypes and must be carefully considered when drawing any biological conclusions based on HPV genotyping data from ICC samples.

Human Papilloma Virus Vaccine for Cervical Cancer Prevention

HPV infection is estimated to be responsible for about 5% of human cancers worldwide. Among all HPV-associated malignancies, cervical cancer is the most important cause of morbidity and mortality worldwide. Cervical cancer is the fourth most common cancer in women worldwide and leading cause of cancer death among females in less developed countries. Persistent HPV infection is a necessary cause of invasive cervical cancer with a prevalence of 99.7% in cervical cancer worldwide.At least 70% of cervical cancers are caused by HPV 16 and HPV 18. HPV vaccination in combination with regular screening offers the most effective way for women to be protected against cervical cancer.The global burden of cervical cancer falls heaviest on the developing countries which haven’t introduced the HPV vaccine as part of their national public health strategy to prevent and control cervical cancer. Different studies showed a drop in the prevalence of HPV associated diseases in vaccinated populations. Sustained efficacy, immunogenicity, and safety of the bHPV vaccine were observed in the final analysis of a follow-up study up to 9.4 years postvaccination. Cervical cancer is a major public health problem in Bangladesh. There has been little success with screening program against cervical cancer in Bangladesh. Therefore, a National HPV Vaccination Program seems to be the window of opportunity to reduce the mortality and morbidity of cervical cancer in Bangladesh.&#x0D; J Bangladesh Coll Phys Surg 2021; 39(2): 123-131

Universal Human Papillomavirus Vaccination and its Impact on the Southern Italian Region.

HPV is still the most common sexually transmitted infection, leading to the onset of many disorders while causing an increase in direct and indirect health costs. High Risk (HR) HPV is the primary cause of invasive cervical cancer and contributes significantly to the development of anogenital and oropharyngeal cancers. The introduction of universal HPV vaccination has led to a significant reduction in vaccine-targeted HPV infections, cross-protective genotypes, precancerous lesions and anogenital warts. Despite the several limitations of HPV vaccination programs, including vaccine type specificity, different schedules, target age-groups and poor communication, the impact has become increasingly evident, especially in countries with high vaccine uptake. We carried out a review of the most recent literature to evaluate the effects of HPV vaccination on vaccinetargeted HPV genotypes and to assess the level of cross-protection provided against non-vaccine HPV types. Subsequently, to assess the rates of HPV infection in a southeast Italian region, we performed an epidemiological investigation on the impact of vaccination on genotypes and on the prevalence and distribution of HPV infection during the twelve-year period 2006-2017 in the Local Health Unit (LHU) of Lecce. The vaccination coverage of about 70% among girls in the LHU led to an initial reduction in vaccine-targeted HPV types and cross-protective genotypes. However, the results on this population should be interpreted cautiously because the period since the start of vaccination is too short and the coverage rate is not yet optimal to evaluate the efficacy of vaccination in lowering the prevalence of non-vaccine HR HPV types in the vaccinated cohort and in older subjects. Nevertheless, it is expected that direct effects will increase further and that herd immunity will begin to emerge as vaccination coverage increases.

J-107 Interrogating the immunologic and microbial cervical microenvironment in HPV infection

Infection with high-risk human papillomavirus (hrHPV) infection in the oral and anogenital mucosa has been confirmed to be a necessary but insufficient cause of invasive cervical cancer (ICC), which is a leading cause of cancer incidence and mortality worldwide. Over the past 2 decades, our understanding of the natural history of cervical hrHPV infection has evolved, especially with regard to the influence of co-infections and the dynamics of the cervical microenvironment. For example, it is now recognized that at least a proportion of hrHPV infections are immunologically controlled for long periods of time in an undetectable (latent) state, at risk of recurrent detection (reactivation) upon immune suppression.1 This phenomenon is most clearly illustrated when comparing the HPV natural history in HIV-infected and HIV-uninfected individuals, where both incident and persistent detection of HPV is proportionally increased with increasing immune suppression.2 Multiple new type cervical HPV detection increases nearly 4-fold within weeks of acute HIV infection, suggesting a key role for tissue resident T-cell memory in control of latent HPV infection.3 In HIV-uninfected women, we have observed polarization toward T-helper type 2 immune profiles of the lower genital tract immune microenvironment. In an older, well-screened US population, HPV positive women exhibited immune profiles similar to those described in allergic inflammation.4 In the developing world, we have reported an increased prevalence of HPV infection at older ages in Amazonian women with soil-transmitted helminth (STH) infection, who showed evidence of Th2-skewed immunity in lower genital tract secretions compared with STH-uninfected women.5 This epidemiologic evidence, combined with experimental animal models of papillomavirus infection, collectively implicate a key role of host immunity in the control of cervical HPV infection and, by extension, risk of cervical cancer. This presentation will make a case that the time has come to move human HPV natural history studies away from traditional designs with large sample sizes and long interval censored sampling (eg, every 6 months) to designs with smaller sample sizes and more frequent sampling density (eg, every week) to allow interrogation of the dynamic interplay between the shifting microenvironment and HPV detection. Prioritizing a focus on understanding the dynamics and immune mediators involved in healthy control of HPV infection may be an overlooked fundamental system component required to fully understand the causes of dysregulation of HPV infection and persistent detection. This represents a paradigm shift in studying the molecular epidemiology of human viral infections, reflects more fully a systems approach to understanding biological complexity, and may lead to development of less invasive interventions at earlier stages in viral natural history to prevent severe pathological outcomes. REFERENCES 1. Gravitt PE. The known unknowns of HPV natural history. J Clin Invest. 2011;121:4593–4599. 2. Strickler HD, Burk RD, Fazzari M, et al. Natural history and possible reactivation of human papillomavirus in human immunodeficiency virus-positive women. J Natl Cancer Inst. 2005;97:577–586. 3. Nowak RG, Gravitt PE, Morrison CS, et al. Increases in human papillomavirus detection during early HIV infection among women in Zimbabwe. J Infect Dis. 2011;203:1182–1191. 4. Marks MA, Viscidi RP, Chang K, et al. Differences in the concentration and correlation of cervical immune markers among HPV positive and negative perimenopausal women. Cytokine. 2011;56:798–803. 5. Gravitt PE, Marks M, Kosek M, et al. Soil-transmitted helminth infections are associated with an increase in human papillomavirus prevalence and a T-helper type 2 cytokine signature in cervical fluids. J Infect Dis. 2016;213:723–730.

The potential of RNA as a target for national screening of pre-cancer.

Whole national screening of pre-cancer is done only in some few countries, dominated by The Netherlands, Denmark, UK, Norway and Finland. These national screenings are done combining national cancer registry, national public health and national medical bodies or hospitals. Until some few years ago national screening was only done using morphological or visual methods or technology. Today a number of molecular methods have been implemented to serve these national screening programs. Based on all the discussions within this review, it is clear that the main driving engine and the cause of cervical pre-cancer and the main cause of invasive cervical cancer is the expression of E6 and E7 oncoproteins from HPV 16, 18, 31, 33 and 45. However, the main challenge is the role of morphology or imaging-based diagnosis in the original definition of pre-cancer disease. This definition is not based on the cause of cervical precancer but based on a complex, subjective, morphological observations. The difference between these two definitions are discussed in this review. The unique discovery done while validating the first standardized detection technology used against mRNA, confirmed that the presence of both abnormal E6 and/or E7 mRNA and protein is the cause of cervical pre-cancer or severe neoplasia and the main cause of invasive cervical cancer. This confirmation was evident even though all these studies were disturbed by the above defined biases from morphology or imaging-based diagnosis. The use of the screening target that cause stable and high expression of the most carcinogenic compounds ever discovered, must cause a more accurate screening program. A number of studies have proved that the detection of E6/E7 mRNA followed-up by indirect or direct treatment in a well-organized national screening program, would reduce the incidence of cervical cancer. This review discusses the main studies involved in the scientific, clinical evaluation and how this unique technology could be used as a new medical gold standard for national screening of cervical pre-cancer.

INVASIVE CERVICAL CANCER IN IBADAN: SOCIO-SEXUAL CHARACTERISTICS, CLINICAL STAGE AT PRESENTATION, HISTOPATHOLOGY DISTRIBUTIONS AND HIV STATUS.

Background:Human Papillomavirus (HPV) infection persistence is the necessary but not sufficient cause of invasive cervical cancer (ICC). The effects of Human Immunodeficiency Virus (HIV) co-infection have been well documented. The purpose of this study was to describe our experience on the clinico-pathological characteristics of patients with cervical cancer and HIV status at a tertiary Hospital in Nigeria.Materials and Methods:This was a descriptive study among ICC patients presenting for clinical staging and biopsy for histological diagnosis at the Obstetrics and Gynaecology outpatient theatre of our hospital between January 2009 and February 2011.Results:Sixteen (6.8%) of the 248 patients with histologically confirmed ICC in this study were HIV positive. The mean age of all the participants was 55.4 (SD±10.2) years with the HIV positive patients’ younger than the HIV-negative and those that declined HIV testing. Coitarche was at lower age (18 [SD±4.4] vs 22[SD±3.4] years vs 24.5[SD±4.4], respectively). The modal lifetime sexual partners were four, one and two, respectively. Clinically, more HIV positive patients, presented at advanced stage of ≥ 2B. Also, the adenocarcinoma histological variant was slightly more among the HIV positive patients.Conclusion:HIV seemed relatively common among ICC patients and they presented at lower ages, at more advanced stages, earlier coitarche and more lifetime sexual partners. The proportion of adenocarcinoma histological types was slightly higher among the HIV positive patients compared with seronegative patients and those with unknown HIV status. Larger studies to substantiate these findings and ICC-HIV causal relationship are required.

High-risk human papillomavirus status and prognosis in invasive cervical cancer: A nationwide cohort study.

BackgroundHigh-risk human papillomavirus (hrHPV) infection is established as the major cause of invasive cervical cancer (ICC). However, whether hrHPV status in the tumor is associated with subsequent prognosis of ICC is controversial. We aim to evaluate the association between tumor hrHPV status and ICC prognosis using national registers and comprehensive human papillomavirus (HPV) genotyping.Methods and findingsIn this nationwide population-based cohort study, we identified all ICC diagnosed in Sweden during the years 2002–2011 (4,254 confirmed cases), requested all archival formalin-fixed paraffin-embedded blocks, and performed HPV genotyping. Twenty out of 25 pathology biobanks agreed to the study, yielding a total of 2,845 confirmed cases with valid HPV results. Cases were prospectively followed up from date of cancer diagnosis to 31 December 2015, migration from Sweden, or death, whichever occurred first. The main exposure was tumor hrHPV status classified as hrHPV-positive and hrHPV-negative. The primary outcome was all-cause mortality by 31 December 2015. Five-year relative survival ratios (RSRs) were calculated, and excess hazard ratios (EHRs) with 95% confidence intervals (CIs) were estimated using Poisson regression, adjusting for education, time since cancer diagnosis, and clinical factors including age at cancer diagnosis and International Federation of Gynecology and Obstetrics (FIGO) stage. Of the 2,845 included cases, hrHPV was detected in 2,293 (80.6%), and we observed 1,131 (39.8%) deaths during an average of 6.2 years follow-up. The majority of ICC cases were diagnosed at age 30–59 years (57.5%) and classified as stage IB (40.7%). hrHPV positivity was significantly associated with screen-detected tumors, young age, high education level, and early stage at diagnosis (p < 0.001). The 5-year RSR compared to the general female population was 0.74 (95% CI 0.72–0.76) for hrHPV-positive cases and 0.54 (95% CI 0.50–0.59) for hrHPV-negative cases, yielding a crude EHR of 0.45 (95% CI 0.38–0.52) and an adjusted EHR of 0.61 (95% CI 0.52–0.71). Risk of all-cause mortality as measured by EHR was consistently and statistically significantly lower for cases with hrHPV-positive tumors for each age group above 29 years and each FIGO stage above IA. The difference in prognosis by hrHPV status was highly robust, regardless of the clinical, histological, and educational characteristics of the cases. The main limitation was that, except for education, we were not able to adjust for lifestyle factors or other unmeasured confounders.ConclusionsIn this study, women with hrHPV-positive cervical tumors had a substantially better prognosis than women with hrHPV-negative tumors. hrHPV appears to be a biomarker for better prognosis in cervical cancer independent of age, FIGO stage, and histological type, extending information from already established prognostic factors. The underlying biological mechanisms relating lack of detectable tumor hrHPV to considerably worse prognosis are not known and should be further investigated.

High-risk human papilloma virus and cervical abnormalities in HIV-infected women with normal cervical cytology.

BackgroundThe prevalence of High-Risk Human papilloma virus (HR-HPV), a necessary cause of invasive cervical cancer (ICC) is relatively high in HIV infected women. Gaps exist in our knowledge of the optimal approaches for managing women who have HR-HPV with normal cervical cytology (NCC) particularly in settings of HIV infection.MethodsBetween May 2012 and June 2013 we conducted a colposcopic assessment of HIV-infected women with prior (NCC) and known HR-HPV status to compare cervical abnormalities in women with and without HR-HPV. Colposcopic examinations were done at the Operation Stop Cervical Cancer (OSCC) unit of the Jos University Teaching Hospital (JUTH), Jos, Nigeria. Abnormal colposcopic finding (ACF) was defined as areas of aceto-white epithelium involving the squamo-coulumnar junction, areas of punctation, mosaic pattern or atypical vessels. We compared proportions of ACF as well as histologic grades of cervical intra-epithelial neoplasia (CIN) in women with or without HR-HPV. Statistical analysis was done on STATA.ResultsWe conducted colposcopic examinations in 78 out of 89 (86.5%) eligible women. The mean age of the cohort was 32.4 years (SD ±4.6) with a median 32 years (IQR 29–36). After a mean follow up time of 20.1 months from the initial cervical pap cytology and HR-HPV testing, we found 12 of 78 (15.4%) women with ACF. The odds for an ACF was statistically higher [OR = 4.0 (95% CI: 1.1-14.7)] in women with HR-HPV compared to those without. Of the twelve women with ACF, subsequent histologic examination of colposcopically directed cervical biopsies confirmed CIN 1 in 4 cases (33.3%), CIN 2 in 1 case (8.3%), CIN 3 in 2 cases (16.7%), carcinoma-in-situ (CIS) in 2 cases (16.7%), and normal cervix in 3 (25.0%). Overall, the proportion of women detected with any grade of CIN was 11.5% (9/78) and 6.4% (5/78) were CIN 2 or greater lesion (CIN2+).ConclusionHIV-infected women with NCC and HR-HPV had a four-fold higher likelihood for an ACF. The practice of early colposcopic examination of HIV-infected women with prior NCC and HR-HPV may increase early detection of higher grade CIN and CIS cancer stages in our setting.

HPV in genital cancers (at the exception of cervical cancer) and anal cancers

Human papillomavirus (HPV) infection has been firmly established as a central and necessary cause of invasive cervical cancer and it has been etiologically linked to other anogenital (vulva, vagina, anus and penis) and head and neck cancers, particularly oropharyngeal. Although being rare, the incidence of some of these cancers in some countries has increased in the last decades. HPV-related anogenital tumors share many risk factors with cervical cancer. The HPV aetiological contribution differs in each anatomical location reflecting differences in the natural history and viral tissue tropism. The highest prevalence of HPV DNA in cancers other than cervix has been described for anal, followed by vagina, penile and vulvar cancers. HPV16 has been described as the most common type detected in all cancer sites with different contributions being the highest in anal carcinoma (around 80% of HPV DNA positive anal cancers) and the lowest in vaginal cancers with a contribution similar to that found in cervical cancers (around 60%). Current HPV vaccines have already demonstrated their efficacy in preventing anogenital pre-neoplastic lesions caused by vaccine HPV types. HPV-based prevention tools like HPV vaccination and to a lesser extend screening (e.g. for anal cancer) can be useful measures for reducing the burden of these anogenital cancers.

Prevalence and Distribution of High-Risk Human Papillomavirus Genotypes in Invasive Carcinoma of the Uterine Cervix in Uruguay

Persistent infection with specific genotypes of human papillomaviruses (HPVs) is the main cause of invasive cervical cancer (ICC). Only a few of the various HPV types account for most of the cases worldwide, and geographical differences in their distribution are evident. Data from locally prevalent genotypes are essential in view of introduction of HPV type-specific prophylactic vaccines. In this work, we have investigated HPV type distribution in samples of ICC cases that occurred in Uruguayan women. DNA extracted from ICC treated in Centro Hospitalario Pereira Rossell of Montevideo between 1999 and 2007 were analyzed. Search and typing were performed by polymerase chain reaction using generic GP5+/GP6+ primers and specific primers for HPV types 16, 18, 33, and 45. Positive GP5+/GP6+ samples, which were negative for all 4 high-risk HPV-specific types screened were further analyzed by sequencing. Human papillomavirus DNA sequences were found in 163 (92.6%) of 176 cases. The most prevalent genotypes were HPV16 (67.6%) and HPV18 (8.5%) followed by HPV45 (6.8%) and HPV33 (3.4%), as single or mixed infection. Other less frequent genotypes were HPV31, HPV35, HPV39, HPV51, HPV52, HPV58, HPV66, and HPV73. The viral type could not be determined (HPV X) in 1 case (0.6%) of the HPV DNA-positive cervical cancers and double infections were found in 1.7% of the cases. The higher percentage of most aggressive HPV (16/18/45) genotypes was detected in cases diagnosed at younger than 60 years old, whereas these genotypes were less frequent in older patients. We conclude that HPV types 16, 18, and 45 have a very high prevalence in ICC of Uruguayan women. Results provide evidence that 16 of 18 infections are more aggressive, but most cancers could be vaccine preventable.

Type-Specific Detection of 30 Oncogenic Human Papillomaviruses by Genotyping both E6 and L1 Genes

Human papillomavirus (HPV) is the principal cause of invasive cervical cancer and benign genital lesions. There are currently 30 HPV types linked to cervical cancer. HPV infection also leads to other types of cancer. We developed a 61-plex analysis of these 30 HPV types by examining two genes, E6 and L1, using MassARRAY matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) (PCR-MS). Two hundred samples from homosexual males (HM) were screened by PCR-MS and MY09/MY11 primer set-mediated PCR (MY-PCR) followed by sequencing. One hundred thirty-five formalin-fixed, paraffin-embedded (FFPE) cervical cancer samples were also analyzed by PCR-MS, and results were compared to those of the commercially available GenoArray (GA) assay. One or more HPV types were identified in 64.5% (129/200) of the samples from HM. Comprising all 30 HPV types, PCR-MS detected 51.9% (67/129) of samples with multiple HPV types, whereas MY-PCR detected only one single HPV type in these samples. All PCR-MS results were confirmed by MY-PCR. In the cervical cancer samples, PCR-MS and GA detected 97% (131/135) and 90.4% (122/135) of HPV-positive samples, respectively. PCR-MS and GA results were fully concordant for 122 positive and 4 negative samples. The sequencing results for the 9 samples that tested negative by GA were completely concordant with the positive PCR-MS results. Multiple HPV types were identified in 25.2% (34/135) and 55.6% (75/135) of the cervical cancer samples by GA and PCR-MS, respectively, and results were confirmed by sequencing. The new assay allows the genotyping of >1,000 samples per day. It provides a good alternative to current methods, especially for large-scale investigations of multiple HPV infections and degraded FFPE samples.

Male Circumcision and Genital Human Papillomavirus

Human papillomavirus (HPV) infection is the principal cause of invasive cervical cancer. There is some evidence that male circumcision (MC) may protect against HPV infection and related disease in both men and women. The purpose of this study was to conduct a systematic review of the literature to assess the association between MC and genital HPV infection indicators including genital warts. A systematic search of Medline was conducted to identify all relevant studies from February 1971 to August 2010. Effect estimates were included in random effects models. A total of 21 studies with 8046 circumcised and 6336 uncircumcised men were included in the meta-analysis. MC was associated with a statistically significant reduced odds of genital HPV prevalence (odds ratio = 0.57, 95% confidence interval: 0.42-0.77). This association was also observed for genital high-risk HPV prevalence in 2 randomized controlled trials (odds ratio = 0.67, 95% confidence interval: 0.54-0.82). No associations were found between MC and genital HPV acquisition of new infections, genital HPV clearance, or genital warts. This meta-analysis shows a robust inverse association between MC and genital HPV prevalence in men. However, more studies are needed to adequately assess the effect of MC on the acquisition and clearance of HPV infections. MC could be considered as an additional one-time preventative intervention likely to reduce the burden of HPV-related diseases both in men and women, particularly among those countries in which HPV vaccination programs and cervical screening are not available.

A novel multiplex real-time PCR assay for the detection and quantification of HPV16/18 and HSV1/2 in cervical cancer screening

Infection with human papillomavirus (HPV), particularly HPV16 and HPV18, is the main cause of invasive cervical cancer, although other factors such as herpes simplex virus (HSV) may act in conjunction with HPV in this context. To explore the possibility of developing a system for rapid diagnosis and clinical screening of cervical cancer, we developed a multiplex real-time PCR assay that can simultaneously detect and quantify HPV16/18 and HSV1/2. To evaluate its possibilities and practical uses, 177 samples collected from patients with suspected HPV and HSV infection in exfoliated cervical cells, genital herpes or labial herpes were tested by multiplex real-time PCR and compared with results obtained by DNA sequencing. Each virus was detected over a range from 1.0 × 101 to 1.0 × 107 copies/reaction. The clinical sensitivity was 100% for HPV16/18 and HSV1/2. The clinical specificity was 97.1% for HPV16, 98.1% for HPV18, 97.0% for HSV1 and 96.0% for HSV2. The kappa value was 0.96 for HPV16, 0.92 for HPV18, 0.94 for HSV1 and 0.93 for HSV2, when DNA sequencing was used as the reference standard. In summary, this novel multiplex real-time PCR allows the rapid and specific detection of HPV16/18 and HSV1/2, as well as coinfection with HPV and HSV, in clinical samples. In the future, this multiplex real-time PCR assay will assist in cervical cancer screening, viral treatment evaluation and epidemiological studies in which high throughput analysis is required.

P2-164 Human papillomavirus, other sexually transmitted infections and risk of cervical cancer. A Nordic Joint Study

IntroductionHuman papillomavirus (HPV) is considered necessary cause of invasive cervical cancer (ICC), but relations between different HPV types and other sexually transmitted infections in cervical carcinogenesis are unresolved. The CCRPB-EU...

Smoking and Passive Smoking in Cervical Cancer Risk: Pooled Analysis of Couples from the IARC Multicentric Case–Control Studies

The independent role of tobacco smoking in invasive cervical cancer (ICC) has been established. We evaluated the potential impact of passive smoking (PS). A pooled analysis of 1,919 couples enrolled in one of seven case-control studies involving cervical carcinoma in situ (CIS) or ICC was investigated. Information on smoking and sexual behavior was collected from interviews. Specimens were taken from the cervix and penis for human papillomavirus (HPV) DNA testing. Three PS risk models were constructed with all couples, couples with monogamous women, and couples with lifetime nonsmoking monogamous women. For the third model, the analysis considered potential misclassification of smoking status and was restricted to the risk period for which the woman was exposed to both HPV, a necessary cause of ICC, and PS. Multivariable unconditional logistic regression was used to estimate associations between CIS or ICC and PS. An increased risk was found among couples with both ever smoking men and women (OR = 2.26; 95% CI: 1.40-3.64). No statistically increased risk of CIS was found with PS in the models analyzed. Similar significant increased risks of ICC with PS was found among all couples (OR = 1.57; 95% CI: 1.15-2.15) and couples with monogamous women (OR = 1.55; 95% CI: 1.07-2.23) but not among lifetime nonsmoking monogamous women married to ever smoking men. PS could not be detected as an independent risk factor of ICC in the absence of active smoking. The combined effects of exposure to active and PS suggest its potential adverse role in cervical carcinogenesis.

Human Papilloma Virus prevalence and type-specific relative contribution in invasive cervical cancer specimens from Italy

BackgroundCervical cancer represents an important global public health problem. It is the 2nd most common cancer among women worldwide. Human Papillomavirus (HPV) infection is now well-established as a necessary cause of invasive cervical cancer (ICC) development. Only a few studies on HPV prevalence and type-specific distribution in ICC have been conducted in Italy.AimTo describe the prevalence of HPV and the HPV type-specific distribution in ICC cases identified in Rome, Italy.Methods140 paraffin embedded tissue blocks of primary ICC diagnosed between 2001 and 2006 were identified at the Regina Elena Cancer Institute in Rome (Italy). HPV was detected through amplification of HPV DNA using SPF-10 HPV broad-spectrum primers followed by DEIA and then genotyping by LiPA25 (version 1).Results134 cases were considered suitable for HPV DNA detection after histological evaluation; and overall, 90.3% (121/134) HPV prevalence was detected. 111 cases had a single HPV type, 4 cases had an uncharacterized type (HPVX) and 6 cases had multiple HPV infections. The five most common single HPV types among positive cases were: HPV16 (71/121; 58.7%), HPV18 (12/121; 9.9%), HPV31, HPV45 and HPV58 (5/121; 4.1% each). 2 (1.5%) of the single infections and 2 (1.5%) of the multiple infections contained low risk types. Statistically significant differences in the relative contribution of HPV18 were found when comparing squamous cell carcinomas with adenocarcinomas.ConclusionsHPV16 and HPV18 accounted for almost 70% of all the HPV positive ICC cases. The study provides baseline information for further evaluation on the impact of recently introduced HPV vaccines in Italy.

Correlation between the presence of high-risk human papillomaviruses and Id gene expression in Syrian women with cervical cancer

Infection by high-risk human papillomaviruses (HPVs) is considered to be the central cause of invasive cervical cancer. Previously reported studies have shown that Id genes regulate cell invasion and metastasis in several human carcinomas including cervical cancer. In order to investigate the correlation between high-risk HPVs and Id genes in human cervical cancer, the presence of high-risk HPVs and their association with Id gene expression was examined using PCR methods and tissue microarray analyses in a cohort of 44 cervical cancer patients from Syria. This study showed that high-risk HPVs were present in 42 samples (95%) that represent invasive cervical cancers and that the most frequent high-risk HPV types in Syrian women were 33, 16, 18, 45, 52, 58, 35, 51 and 31. Furthermore, the expression of E6 oncoprotein of high-risk HPVs was found to correlate with overexpression of Id-1, but not of Id-2, Id-3 or Id-4 in the majority of invasive cervical cancer tissue samples. These data suggest that high-risk HPVs can enhance the progression of human cervical cancer through Id-1 regulation.

Detection of Human Papillomavirus DNA in Cutaneous Squamous Cell Carcinoma among Immunocompetent Individuals

The presence of certain types of human papillomavirus (HPV) is a known risk factor for the development of anogenital squamous cell carcinomas (SCCs). A similar association has been hypothesized for cutaneous SCCs, although, to our knowledge, no studies to date have combined sensitive HPV DNA detection techniques with epidemiologic data controlling for known risk factors to explore the association. We designed a case-control study examining HPV prevalence using highly sensitive PCR-detection assays in tissue samples from 85 immunocompetent patients with histologically confirmed SCCs and 95 age-matched individuals without a prior history of skin cancer. A standardized interview was administered to all study subjects to collect information pertaining to potential confounding variables. The overall detection rate of HPV DNA was high in case lesions (54%) and perilesions (50%) and in both sun-exposed normal tissue (59%) and non-sun-exposed normal tissue (49%) from controls. In comparing case tissue to control tissue, there was no differential detection of HPV DNA across various HPV species. However, HPV DNA from beta-papillomavirus species 2 was more likely to be identified in tumors than in adjacent healthy tissue among cases (paired analysis, odds ratio=4.0, confidence interval=1.3-12.0). The high prevalence of HPV DNA detected among controls suggests that HPV DNA is widely distributed among the general population. However, the differential detection of HPV beta-papillomavirus species in tumors among cases suggests that certain HPV types may be involved in the progression of cutaneous SCCs.

Human papillomavirus (HPV) genotype distribution in invasive cervical cancers in France: EDITH study

Invasive cervical cancer (ICC) remains a significant cause of morbidity and mortality in France. Since human papillomavirus (HPV) is the necessary cause of ICC, the aim of this study was to assess the type-specific prevalence of HPV in ICC in France in order to locally evaluate the potential benefit of an HPV 16/18 L1 virus-like particles (VLP) vaccination. A total of 516 histological specimens collected in 15 centers were analyzed. Among them, 86% had a diagnosis of squamous cell carcinoma (SCC) whereas 14% were adenocarcinomas (ADC). HPV genotyping was performed using the INNO-LiPA assay allowing the specific detection of 24 HPV genotypes both high risk (HR) and low risk (LR). The overall HPV prevalence in ICC was 97%. The most prevalent genotypes were HPV 16 (73%) and HPV 18 (19%) followed by HPV 31 (7%), 33, 68, 45, 52 and 58 (4.1-2.3%). HPV 16 and/or 18 were associated with 82% of ICC, 10% being HPV 16 and 18 coinfections. While HPV 16 was the most prevalent type in both SCC (74%) and ADC (64%), HPV 18 was by far more prevalent in ADC (37%) compared to SCC (16%; p < 0.001). Multiple infections with at least two different HR HPV genotypes were observed in 22% of ICC. Given the high HPV 16/18 prevalence and taking into account possible production of crossneutralizing antibodies against other HPV types, HPV 16/18 L1 VLP vaccination would be expected to significantly reduce the burden of ICC in France.