HPV-related Cervical Disease Research Articles

Distribution of high-risk human papillomavirus genotypes among HIV-negative women with and without cervical intraepithelial neoplasia in South Africa.

ObjectiveLarge studies describing the profile of high-risk Human papillomavirus (hrHPV) genotypes among women in sub-Saharan Africa are lacking. Here we describe the prevalence and distribution of hrHPV genotypes among HIV-negative women in South Africa, with and without cervical intraepithelial neoplasia (CIN).MethodsWe report data on 8,050 HIV-negative women, aged 17–65 years, recruited into three sequential studies undertaken in Cape Town, South Africa. Women had no history of previous cervical cancer screening. Cervical samples were tested for hrHPV DNA using the Hybrid Capture 2 (HC2) assay and all positive samples were genotyped using a PCR-based assay (Line Blot). Women underwent colposcopy and biopsy/endocervical curettage to determine CIN status. The prevalence and distribution of specific hrHPV genotypes were examined by age and CIN status.ResultsOverall, 20.7% (95% CI, 19.9–21.6%) of women were hrHPV-positive by HC2, with women with CIN having the highest rates of positivity. Prevalence decreased with increasing age among women without CIN; but, a bimodal age curve was observed among women with CIN. HPV 16 and 35 were the most common hrHPV genotypes in all age and CIN groups. HPV 45 became more frequent among older women with CIN grade 2 or 3 (CIN2,3). Younger women (17–29 years) had more multiple hrHPV genotypes overall and in each cervical disease group than older women (40–65 years).ConclusionHPV 16, 35, and 45 were the leading contributors to CIN 2,3. The current HPV vaccines could significantly reduce HPV-related cervical disease; however, next generation vaccines that include HPV 35 and 45 would further reduce cervical disease in this population.

Biomarkers of Cervical Dysplasia and Carcinoma

Although cervical cytology screening has decreased the incidence of cervical cancer in industrialized countries, HPV-related cervical disease, including premalignant and malignant lesions, continues to represent a major burden on the health care system. Some of the problems include the potential for either under- or overtreatment of women due to decreased specificity of screening tests as well as significant interobserver variability in the diagnosis of cervical dysplastic lesions. Although not completely elucidated, the HPV-driven molecular mechanisms underlying the development of cervical lesions have provided a number of potential biomarkers for both diagnostic and prognostic use in the clinical management of these women.

Abstract B77: High-risk human papillomavirus genotypes among HIV-negative black women with or without cervical disease in South Africa

Abstract Objective: Persistent high-risk human papillomavirus (HPV) infections are associated with cervical pre-malignant lesions and cervical cancer. Women in sub-Saharan Africa are at high risk of advanced cervical disease as well as cervical cancer. We examined the prevalence and distribution of high-risk HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 66) among HIV-negative Black women enrolled in three cervical cancer screening studies in Cape Town, South Africa. Knowledge of the epidemiology of high-risk HPV types in this population will help target prevention interventions. Methods: Black women, aged 17-65 years, were tested for high risk HPV DNA using the Hybrid Capture 2 (HC2) assay and positive samples were typed by PCR to determine the specific genotype. Cervical disease status was determined by colposcopy and cervical biopsy. The prevalence and distribution of high-risk HPV types as well as the frequency of multiple high-risk HPV types were examined by age and cervical disease. Results: Among 8,073 HIV-negative women included in the study, 20.9% (n=1689) were HC2 HPV DNA positive; and, in 73.62% (n=1223/1661) of these positives, a specific high-risk HPV type was detected. Overall, the prevalence of high-risk types was 19.94%. The most common high-risk types across cervical disease status were HPV 16 and 35. Among women without cervical disease, younger women, aged 17-29 years, had the highest prevalence of high-risk types in comparison to older women. Among women with CIN 2 or CIN 3, a higher prevalence of HPV 16 and 45 was observed among older women, aged 40-65 years, than among younger women, aged 17-29 years; as for HPV 35, the prevalence was stable across age groups. The distribution of HPV 16, 35, and 33 were statistically significantly higher among HC2 DNA positive, high-risk HPV positive women with advanced cervical disease than women with no cervical disease or CIN 1 (p-values < 0.02). Younger women, aged 17-29 years, had more multiple types overall and across all cervical disease status than older women, aged 40-65 years. Conclusion: HPV 16 and 35 are the leading contributors of cervical disease among HIV-negative Black South African women. Therefore, the HPV vaccine has the capacity to result in significant reduction in HPV-related cervical disease in this population. Citation Information: Cancer Prev Res 2010;3(12 Suppl):B77.

The Impact of HAART on HPV-Related Cervical Disease

highly active antiretroviral therapy (HAART) has had an unequivocally positive impact on morbidity and mortality in HIV-infected individuals. These benefits have clearly extended to some HIV-related malignancies, including Kaposi's sarcoma and non-Hodgkin's lymphoma. The impact of HAART on cervical cancer, however, remains uncertain. The objective of this review is to summarize the last ten years of registry-based and clinical research into the impact of HAART on human papillomavirus (HPV) related cervical disease. compared to their HIV-uninfected counterparts, HIV-infected women have an increased prevalence of HPV infection, increased risk of progression of HPV-related cervical disease, and an increased risk of invasive cervical cancer. While the partial immune reconstitution afforded by HAART might be expected to decrease susceptibility to HPV infection and cervical disease, the local effects of improved immunosurveillance on the cervix are uncertain and the increased longevity of patients on HAART may increase risk of exposure to HPV and provide the time required for progression of cervical disease. Registry-based evidence has been consistent in identifying the lack of decrease in cervical cancer incidence in the HAART era. Clinical research on the subject, however, has produced conflicting evidence with regards to both the effect of HAART on HPV infection and its impact on cervical disease progression/regression. the incidence of cervical cancer has not decreased in the HAART-era. Furthermore, clinical research has not shown a clear benefit of HAART in decreasing HPV-related cervical disease in HIV-infected women. A better understanding of this subject will have an impact on cervical disease surveillance practices.

Total burden and incidence of in situ and invasive cervical carcinoma in Michigan, 1985-2003.

With the recent licensure of a vaccine that protects against human papillomavirus (HPV) types 16 and 18, US women are expected to experience lower rates of cervical cancer. However, surveillance systems must be in place in the US to measure the real-world effectiveness of vaccination programs. Although population-based registries will provide invasive cervical cancer (ICC) incidence and burden data, the impact of HPV vaccine on cervical cancer will not be measurable for several decades. Cervical carcinoma in situ (CIS), a cervical precancer and the immediate precursor to ICC, is an earlier presentation of HPV-related cervical disease that affects a much larger number of women, and monitoring trends in CIS could provide an earlier measure of HPV vaccine effectiveness. Currently, registries do not collect data on CIS except for the state cancer registry in Michigan, which has been continually collecting CIS data since 1985. All cases of CIS and ICC diagnosed from 1985 through 2003 in the Michigan registry were identified. Available data include age at diagnosis, race, morphologic tumor type, and tumor behavior. There were 58,144 cases of CIS and ICC, of which 48,272 (83.0%) were CIS and 9872 (17.0%) were ICC. There were 2928 CIS cases and 413 ICC cases diagnosed in Michigan during 2003, compared with 1577 CIS and 516 ICC cases reported in 1985. Age-adjusted CIS rates increased from 1985 (31.7 per 100,000) to 2003 (59.2 per 100,000); rates of CIS were highest among women age <40 years. Age-adjusted rates of ICC have declined since 1990, when the rate was 14 per 100,000 females; the rate is currently down to 7.8 per 100,000 females in 2003. The rising rates of CIS in women age <40 years, coupled with declining rates of ICC, suggests the important role of early CIS detection in the prevention of ICC. The CIS trend data, used in conjunction with ICC trend data, help to provide a more thorough picture of cervical disease in the state and also provide baseline data regarding CIS burden in a prevaccine era. The experiences of the Michigan registry can inform the development of CIS surveillance in other registries, an important potential registry role relative to monitoring cervical cancer prevention efforts.

Genital HPV enfeksiyonu ve koruyucu HPV aşıları Çağrılı Editör

Human Papillomavirus HPV infection is accepted as the cause of cervical cancer Besides HPV infection is a growing health problem Prophylactic HPV vaccines immunologically block the virus by increasing the neutralizing antibodies in cervical secretions These vaccines aim to stop the development of cervical preinvasive lesions and cervical cancer The prospective studies proved that these vaccines were well tolerated; highly immunogenic resulting in high antibody titers decreasing persistent HPV infections and HPV related cervical disease It can be postulated that vaccination against HPV will be superior to current protection strategies Turk Arch Ped 2008; 43: 1 8 Key words: Cervical cancer HPV infection

Öksürük solunum zorluğu üç aylıktan beri süregelen döküntü ve otit yakınması ile getirilen bir yaşında erkek hasta Ayın Olgusu

Human Papillomavirus HPV infection is accepted as the cause of cervical cancer Besides HPV infection is a growing health problem Prophylactic HPV vaccines immunologically block the virus by increasing the neutralizing antibodies in cervical secretions These vaccines aim to stop the development of cervical preinvasive lesions and cervical cancer The prospective studies proved that these vaccines were well tolerated; highly immunogenic resulting in high antibody titers decreasing persistent HPV infections and HPV related cervical disease It can be postulated that vaccination against HPV will be superior to current protection strategies Turk Arch Ped 2008; 43: 1 8 Key words: Cervical cancer HPV infection

Prevalence of Oncogenic HPV Types in Sardinia (Italy): Implications for the Impact of Prophylactic Anti-HPV Vaccines

Infection with high-risk HPV genotypes is considered an essential step in cervical carcinogenesis. Recently, prophylactic anti-HPV vaccines have shown to provide effective protection in clinical trials. However, protection appears to be type-restricted, thus, its real extent will depend on HPV types prevalence in the target population. Here we report HPV prevalence in 555 Italian women with various stages of HPV-related cervical disease (343 CIN1/L-SIL, 156 CIN2-3/HIGH-SIL, 43 invasive squamous cervical carcinoma and 13 adenocarcinoma), as well as in 315 women with smears negative for intraepithelial lesions or malignancy (NIL). HPV was found in 50.7% of CIN1/L-SIL, 87.2% of CIN2-3/HIGH-SIL, 97.7% of squamous carcinomas, 69.2% of adenocarcinomas and in 29.5% of NIL. HPV 16 was present in 69.0% of squamous carcinomas, 58.8% of CIN2-3/HIGH-SIL, in 22.9 and 16.1% of CIN1/L-SIL and NIL, respectively. HPV 18 was found in 7.3% and 4.8%, respectively, while in 35.3% and 26.2% of CIN2-3/HIGH-SIL and invasive carcinomas, respectively, were present high-risk HPV types other than type 16 and 18. Based on these data, it is expected that current HPV prophylactic vaccines could effectively prevent up to 70% of invasive cervical cancers and a slightly smaller proportion of high-grade lesions, in our population.

HAART Use in Women With HIV and Influence on Cervical Intraepithelial Neoplasia: A Clinical Opinion

Study the role of highly active antiretroviral therapy (HAART) in cervical disease in women with human immunodeficiency virus (HIV) and human papillomavirus (HPV) infections. A systematic review of current literature and the results summarized in the following headings: HIV and cytological evidence of disease, HIV and HPV, and HAART and HIV in women with HPV-associated cervical disease. Limited data is available to study the influence of HAART on HPV-related cervical disease in women with HIV. There is evidence that the use of HAART may lead to immune restoration and thereby prevent severe recurrent HPV disease, thus influencing associated cervical disease. Little data is available on HAART and its role in HPV-associated cervical disease in women with HIV. Immune restoration may decrease the severity and recurrence of HPV infection and potentially impact cervical disease. Population-based studies are needed to further evaluate the role of HAART in HPV associated cervical disease.

Ki-67, cyclin E, and p16INK4 are complimentary surrogate biomarkers for human papilloma virus-related cervical neoplasia.

Prior studies of Ki-67, cyclin E, and p16 expression have suggested that these biomarkers may be preferentially expressed in cervical neoplasia. This study examined and compared the distribution of staining for these three antigens in 1) normal and reactive epithelial changes, 2) diagnostically challenging cases (atypical metaplasia and atypical atrophy), 3) squamous intraepithelial lesions (SIL), and 4) high-and low-risk human papilloma virus (HPV) type-specific SIL. One hundred four epithelial foci from 99 biopsies were studied, including low-grade squamous intraepithelial lesions (LSIL; 24), high-grade squamous intraepithelial lesions (HSIL; 36), mature or immature (metaplastic) squamous epithelium (29), and atrophic or metaplastic epithelium with atypia (15). Cases were scored positive for Ki-67 expression if expression extended above the basal one third of the epithelium, for cyclin E if moderate to strong staining was present, and for p16 if moderate to strong diffuse or focal staining was present. HPV status was scored by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of extracted DNA. Immunohistochemical findings were correlated with histologic and viral data. Overall, a histologic diagnosis of SIL correlated strongly with all of the biomarkers used (p <0.001). Positive scores for Ki-67, cyclin E, and p16 were seen in 68.4%, 96.7%, and 100% of LSILs and 94.7%, 91.6%, and 100% of HSILs, respectively. Positive predictive values of these three biomarkers for HPV were 82.4%, 89.5%, and 91.4%, respectively. The positive predictive value for HPV of either cyclin E or p16 was 88.7%. Strong diffuse staining for p16 was significantly associated with high-risk HPV-associated lesions. Normal or reactive epithelial changes scored positive for the three biomarkers in 7.7%, 8.0%, and 12%, respectively. Limitations in specificity included minimal or no suprabasal staining for Ki-67 in immature condylomas and occasional suprabasal staining of reactive epithelial changes (10%), diffuse weak nuclear cyclin E staining in some normal or metaplastic epithelia, and diffuse weak basal p16 staining and occasional stronger focal positivity in normal epithelia. Ki-67, cyclin E, and p16 are complementary surrogate biomarkers for HPV-related preinvasive squamous cervical disease. (Because cyclin E and p16 are most sensitive for LSIL and HSIL [including high-risk HPV], respectively, use of these biomarkers in combination for resolving diagnostic problems, with an appreciation of potential background staining, is recommended.)

Definition of human papillomavirus type 16 DNA levels in low and high grade cervical lesions by a simple polymerase chain reaction technique.

Human papillomavirus type 16 (HPV 16) is associated with a high proportion of cervical cancers and pre-cancers but has also been reported by some workers to be widely distributed in the normal population. Using a semi-quantitative polymerase chain reaction technique (PCR) operated with carefully regulated sensitivity we have established two distinct levels of HPV 16 DNA which distinguish between high and low grade cervical lesions. The potential use of such an approach in the understanding and management of HPV related cervical disease is discussed.

Prediction of ‘High-Risk’ Cervical Papillomavirus Infection by Biopsy Morphology

Certain human papillomavirus (HPV) types (such as type 16) have been linked to high-grade precancers and invasive carcinomas of the cervix. However, the accuracy with which morphologic characteristics will predict the presence and type of HPV infection is controversial. Three pathologists independently classified 102 consecutive cervical biopsies with the use of specific criteria and correlated their findings with the presence of HPV 11, 16, and 18 RNA sequences by in situ hybridization. Based on the presence and distribution of nuclear atypia, abnormal mitotic figures, and koilocytosis, biopsies were classified into borderline condyloma, condyloma, borderline cervical intraepithelial neoplasia (CIN) with koilocytotic atypia (CINK), and CIN. Two or more observers agreed on the diagnosis in 96% of cases. HPV 16-related sequences alone were detected in 0% of borderline condylomata, 17% of flat condylomata, 43% of borderline CINK, 67% of CINK, and 77% of CIN lesions. Other HPVs, including those producing signals with more than one probe, were present in 0, 50, 14, 9, and 0% of these lesions, respectively. The authors data suggest that consistent identification of HPV-related cervical disease requires the presence of specific cytologic changes. In the authors' series, when HPV-related disease is present, CIN is the most common lesion and most (71%) contain HPV 16-related nucleic acids. Thus, a high proportion (88%) of histologic abnormalities associated with HPV-16 could be distinguished as CIN by morphologic characteristics alone, and this distinction could be made by most observers.