Association Of Human Papillomavirus Infection Research Articles

Expression of toll-like receptor 4 is down-regulated during progression of cervical neoplasia.

Chronic infection and inflammation are among the most important factors contributing to cancer development and growth. Toll-like receptors (TLRs) are important families of pattern recognition receptors, which recognize conserved components of microbes and trigger the immune response against invading microorganisms. TLR4 is the signaling receptor for lipopolysaccharide (LPS), the endotoxic component of Gram-negative bacteria. Recent studies demonstrate that TLRs are expressed in some tumor cells, and that the expression of TLRs in these cells is associated with tumorigenesis. Cervical intraepithelial neoplasia (CIN) is a key stage in the development of cervical cancer and human papillomavirus (HPV) infection is an essential factor in cervical carcinogenesis. As the cervix is in constant contact with bacteria, especially Gram-negative bacteria, we hypothesize that TLR4-mediated bacterial stimulation may be involved in the tumorigenesis of cervical cancer. In the present study, the expression and distribution of TLR4 in CIN and cervical squamous carcinoma were investigated by immunohistochemistry. To our surprise, we observed a decrease in the expression of TLR4 during the progression of cervical neoplasia and this down-regulation of TLR4 appeared to be associated with the expression of P(16INK4A) which is a crucial marker of HPV integration into host cells. These data offer further insight regarding the association of HPV infection and TLR signaling during the carcinogenesis of cervical cancer.

Detection of mucosal and cutaneous human papillomaviruses in oesophagitis, squamous cell carcinoma and adenocarcinoma of the oesophagus

Background Epidemiologic evidence points to a connection between viral infections by the human papillomavirus (HPV) and a subgroup of squamous cell carcinomas of the oropharynx. Still controversial is the association of HPV infection with oesophageal neoplasia. Objectives To investigate the presence of mucosal as well as cutaneous HPVs in squamous cell carcinoma and adenocarcinoma of the oesophagus. Study design HPV DNA has been searched by PCR and characterized by nucleotide sequence analysis in paraffin-embedded biopsies from Italian patients with oesophageal squamous cell carcinoma ( n = 36), sarcomatoid cell carcinoma ( n = 1), adenocarcinoma ( n = 20) and oesophagitis lesions ( n = 27). Results A broad spectrum of HPVs, primarily cutaneous types was demonstrated in 27.8% (10/36) of squamous cell carcinomas with a significantly higher frequency in well (G1) and moderately (G2) differentiated grades (47.3%, 9/19) compared to poorly (G3) differentiated (5.9%, 1/17) squamous cell carcinoma ( p = 0.008), and in 10% (2/20) of adenocarcinomas and in 29.6% (8/27) of oesophagitis. HPV types detected included mucosal types HPV 6 and 16, cutaneous types HPV 8, 15, 20 and 25; and the putative new HPV types X14, X15, DL473, PPHL1FR and CJ198. Conclusions There is no evidence of any association between mucosal HPVs and oesophageal neoplasia. The cutaneous HPVs are detected at low frequency in adenocarcinoma and poorly differentiated squamous cell carcinoma, while they are frequently detected in oesophagitis and in well and moderately differentiated squamous cell carcinoma suggesting their tropism for keratinized tissue, although a significant association with such neoplasias cannot be drawn.

HPV genotype prevalence in cytologically abnormal cervical samples from women living in south Italy

Human papillomavirus (HPV) infection is the commonest sexually transmitted infection, and high-risk HPV types are associated with cervical carcinogenesis. This study investigated: the HPV type-specific prevalence in 970 women with an abnormal cytological diagnosis; and the association of HPV infection and cervical disease in a subset of 626 women with a histological diagnosis. HPV-DNA was researched by nested PCR/sequencing and the INNOLiPA HPV Genotyping assay. The data were analysed by the chi-square test ( p ≤ 0.05 significant). Overall, the HPV prevalence was 37.7%; high-risk genotypes were found in 88.5% of women and multiple-type infections in 30.9% of the HPV-positive women. The commonest types were HPV-16 (8.2%), HPV-6 (5.0%), HPV-51 (4.2%) and HPV-53 (3.6%). Among the women with histological diagnosis, HPV was evident in 19.9% of those without lesions, 65.8% of those with low-grade lesions and 100% ( p = 0.002) of those with high-grade lesions. The commonest types were HPV-16 (in 14.7% low-grade and 42.8% high-grade lesions), HPV-31 (4.7% and 14.3%, respectively) and HPV-33 (2.0% and 14.3%, respectively). Two high-grade lesions contained exclusively one uncommon type, namely, HPV-83 and -85. This study confirmed the high prevalence of HPV infection and high-risk genotypes among women with cervical abnormalities living in Italy. These data may contribute to increasing the knowledge of HPV epidemiology and designing adequate vaccine strategies.

Prevention of cervical cancer

This article reviews the burden of cervical cancer in South Africa and shows that it remains the most common cancer among South African women, particularly women with least access to cervical cancer screening. It explains the rationale behind the South African cervical cancer screening policy, which is to offer all asymptomatic women three free cervical smears in a lifetime, beginning at age 30, 10 years apart. Further, it illustrates that cervical cancer screening offers unique opportunities for prevention at both the primary and secondary levels. The causal association of human papillomavirus infection of the cervix and the possibility for vaccination against the virus is discussed. The history of screening in South Africa and why it has failed to make a major impact to date on the morbidity and mortality of cervical cancer is also discussed. Finally, possible alternative approaches to cervical cytology for the prevention of cervical cancer are briefly reviewed.

High Association of Human Papillomavirus Infection with Oral Cancer: A Case-Control Study

The aim of the present study was to determine the association of high-risk human papillomavirus (HR-HPV) in Mexican individuals with oral squamous cell carcinoma (OSCC) and their association with various risk factors. We designed a matched case-control study. Cases were individuals with newly diagnosed OSCC, age- and sex-matched with controls (1:4). Demographic and clinical data were obtained; also a self-administered questionnaire about sexual behavior was included. DNA from oral brushing was purified to amplify HPV-DNA through MY09/MY11 and GP5+/GP6+ primers and subsequently subjected to sequencing. Conditional regression models were built to calculate odds ratios (ORs) and 95% confidence intervals (CI). Sixty two cases and 248 controls (53.2% males), median age 62 years (Q1-Q3=54-72 years) were included. HPV prevalence was 43.5% in cases and 17.3% in controls (HR-HPV: 37.1% cases, 9.7% controls). The most frequent types in cases were HPV-16 and HPV-18 (55.6 and 18.5%). The presence of HR-HPV was associated with OSCC (OR=6.2; 95% CI: 2.98-12.97) controlling for the most common risk factors. An interaction between smoking and drinking was detected, and family history of cancer was also significant (OR: 3.61; 95% CI=1.44-8.99). Early age at first sexual intercourse and large number of lifetime sexual partners showed an association with HR-HPV (p=0.019 and p=0.033, respectively). Oral HR-HPV was strongly associated with OSCC, suggesting that HPV-16 and -18 are risk factors for oral cancer in Mexican patients. A significant association of tobacco and alcohol was confirmed. In addition, family history of cancer was associated with OSCC. The results underline the role of HPV in OSCC and its multifactorial etiology.

Evidence for an association of human papillomavirus infection and colorectal cancer

Aim To investigate the presence of human papillomavirus (HPV) in colorectal carcinomas and the correlation of the viral infection with prognostic factors for the disease outcome. Methods Seventy-two patients with primary colorectal adenocarcinoma were studied. From each patient two tissue samples were collected: one sample of the tumor and one sample of normal colorectal tissue from an area located 15 cm away from the tumor. Samples of colorectal mucosa obtained from 30 individuals without malignant disease were also studied as control group. Tissues were initially analyzed through MY/GP nested polymerase chain reaction (PCR) and through GP5+/GP6+ auto-nested PCR. Specific primer sets targeting the E6/E7 region of the HPVs 6, 11, 16, 18, 31, 33, 45 were used for typing. Direct DNA sequencing was conducted to confirm positive PCR results. Results HPV DNA was detected in colorectal specimens of 60 patients with cancer (83.3%), but in none of the tissues from the non-malignant control group ( p < 0.001). Twenty-three cancer patients had HPV DNA detected in both the tumor and the matched normal tissue, 23 had HPV only in the tumor, and 14 had HPV only in the normal colorectal tissue. HPV16 was the viral type most frequently detected, being present in 41 out of 60 positive cases (68.3%). No correlation between the presence of the virus and specific prognostic predictors for the disease outcome was observed. Conclusion HPV is present in the colon and rectum of most patients with colorectal adenocarcinoma, suggesting that this virus may be related to the pathogenesis of colorectal cancer.

Frequency of human papillomavirus infection in oesophageal squamous cell carcinoma in Iranian patients

Human papillomavirus (HPV) is 1 of the possible aetiological factors in the development of oesophageal squamous cell carcinoma (ESCC). We aimed to study the role of HPV in ESCC. 140 cases of ESCC were analysed for the HPV DNA by polymerase chain reaction (PCR) using GP5+/GP6+ primers for L1 open reading frame (ORF) to amplify a 150 bp segment of HPV L1 ORF. This region was subsequently sequenced to identify the type of HPV. Of the 140 patients enrolled to our study 50.7% were female and 49.3% were male, aged between 20 and 81 y. 33 tumour specimens (23.6%) and 12 (8.6%) non-involved tumour margins were HPV positive. From HPV positive tumour cases 36% were positive in tumour margins. The HPV positive cases were 21.7% male and 25.3% female. There is no correlation between presence and types of HPV with patients' gender and age. The frequency of HPV subtypes in tumoural regions was as follows: HPV-16, 60.6%; HPV-18, 30.3%; HPV-33, 6.1%; and HPV-31, 3%. We found only HPV-16 in tumour margins. Our results are consistent with HPV studies conducted in other high-risk areas for ESCC and provided further evidence to support a causal association of HPV infection with ESCC.

Correlation between human papillomavirus infection and bladder transitional cell carcinoma

BackgroundTo determine the association of human papillomavirus infection (HPV) and transitional cell carcinoma (TCC).MethodsUsing polymerase chain reaction, fifty-nine bladder tissue specimens of patients with transitional cell carcinoma of bladder compared with 20 bladder samples of cases with non-neoplastic disorders.ResultsMale to female ratio was similar in the two groups (50/9 vs. 16/4, P = 0.62). Mean age was 67 ± 10.8 years and 52 ± 20.3 years in the case and control groups, respectively (P = 0.6). Of the 59 tissue specimens with diagnosis of transitional cell carcinoma, HPV DNA was detected in 21 (35.6%) samples, while it was present in only one sample (5%) in the control group (P = 0.008). HPV18 was the most common type of virus with the incidence rate of 17/21(81%).ConclusionHPV might play a causative role in transitional cell carcinoma of bladder in our geographic area.

Association of Human Papillomavirus Infection with Palmoplantar Epidermal Cysts in Korean Patients

Human papillomavirus (HPV) infection can develop into many different kinds of diseases ranging from simple warts to carcinoma in situ. Some investigators have recently suggested that HPV infection could be closely related to palmoplantar epidermal cysts. The aim of this study was to determine the existence of HPV and its subtype in palmoplantar epidermal cysts of Korean patients. We investigated 13 cases of palmoplantar epidermal cysts by employing clinical, histopathological and immunohistochemical examinations. In addition, PCR was performed using HPV 57 and 60 type primers. Four of the 13 cases (30.8%) showed the distinct histopathological features of palmoplantar epidermal cysts such as parakeratosis, vacuolar structures and eosinophilic inclusion bodies and these 4 cases showed positive immunohistochemical staining reactions for HPV. PCR for HPV detected type 60-positive bands in 5 of the 13 cases (38.5%), which included the 4 cases that were positive for immunohistochemical staining. These results show that HPV is associated with some cases of palmoplantar epidermal cysts in Korean patients, suggesting that HPV may play a role in the pathogenesis of these cysts.

Human Papillomavirus Gene Expression in Cutaneous Squamous Cell Carcinomas from Immunosuppressed and Immunocompetent Individuals

Epidermodysplasia verruciformis (EV)-type human papillomavirus (HPV) DNA have been detected by PCR in squamous cell carcinomas (SCC) from both organ transplant recipients (OTR) and immunocompetent individuals. Their role in skin cancer remains unclear, and previous studies have not addressed whether the viruses are transcriptionally active. We have used in situ hybridization to investigate the transcriptional activity and DNA localization of HPV. EV-HPV gene transcripts were demonstrated in four of 11 (36%) OTR SCC, one of two (50%) IC SCC, and one of five (20%) OTR warts positive by PCR. Viral DNA co-localized with E2/E4 early region gene transcripts in the middle or upper epidermal layers. Non-EV cutaneous HPV gene transcripts were demonstrated in one of five (20%) OTR SCC and four of 10 (40%) OTR warts. In mixed infections transcripts for both types were detected in two of six (33%) cases. Our results provide evidence of EV-HPV gene expression in SCC; although only a proportion of tumors were positive, the similarly low transcriptional activity in warts suggests this is an underestimate. These observations, together with emerging epidemiological and functional data, provide further reason to focus on the contribution of EV-HPV types to the pathogenesis of cutaneous SCC.

HPV DNA in clinically different variants of oral leukoplakia and lichen planus

Objectives Our objectives were to determine the prevalence of human papillomavirus (HPV) infection in oral leukoplakia (OL) and oral lichen planus (OLP) in comparison with that in healthy oral mucosa, also conditionally to age, gender, smoking, and drinking habits of patients, so as to investigate any possible association of HPV infection with a specific clinical variant of OL or OLP. Study design We did research on HPV DNA in 68 cases of OL (homogeneous form [H] in 45 cases and nonhomogeneous form [non-H] in 23 cases), and in 71 cases of OLP (nonatrophic/erosive form [non-AE] in 27 cases, atrophic/erosive form [AE] in 44 cases). HPV DNA was investigated in exfoliated oral mucosa cells by nested PCR ( nPCR: MY09-MY11/GP5-GP6) and the HPV genotype determined by direct DNA sequencing. Results HPV DNA was found in 17.6% of OL, in 19.7% of OLP, and in 5.6% of controls, with a statistically significant higher risk of HPV infection in both lesion groups (for OL: P = .01; Odds Ratio [OR] = 3.64; 95% CI: 1.21-10.80; for OLP: P = .005; OR = 4.17; 95% CI: 1.41-12.18). Demographic variables analysis showed that the only significant association was between HPV status and current smoking in OL patients (OR' = 3.40; 95% CI: 1.0-11.59). HPV DNA was found in 20% of H OL and 13% of non-H OL, without any association with the clinical variant ( P = .73; OR = 0.60; 95% CI: 0.14-2.48). HPV DNA was found in 18.5% of non-AE OLP and 20.4% of AE OLP, without any significant association with the clinical variant ( P = .84; OR = 1.13; 95% CI: 0.335-3.816). HPV-18 was the most frequently detected genotype (9/12 and 10/14 of HPV-positive OL and OLP, respectively), followed by HPV-16 (2/12 OL and 2/14 OLP), HPV-33 (1/12 OL), HPV-31 (1/14 OLP), and HPV-6 (1/14 OLP). Conclusions An increased risk of HPV infection was found in OL and OLP; however, no specific clinical variant of OL or OLP was noted to be associated with HPV infection. It is not possible to predict the likelihood of HPV infection from the clinical features of OL and OLP.

Association of HPV infection with prognosis after neoadjuvant chemotherapy in advanced uterine cervical cancer

Whether the human papillomavirus (HPV) status of the tumor affects the sensitivity to neoadjuvant chemotherapy, and the prognosis in advanced uterine cervical cancer (FIGO stage III or higher) remains unknown. We examined the HPV status of 43 patients who had received CDDP therapy by balloon-occluded arterial infusion (BOAI), as neoadjuvant chemotherapy for advanced uterine cervical cancer (squamous cell carcinoma) stage III or higher. DNA was extracted from formalin-fixed, paraffin-embedded tumor samples obtained by punch biopsy before the neoadjuvant chemotherapy. The detection of HPV and its typing were analyzed by a polymerase chain reaction (PCR)-based assay using consensus primers for the L1 consensus regions. HPV DNA was detected in all 43 patients (100%): 29 cases with HPV 16 (67.4%), 5 cases with HPV 33 (11.6%), 4 cases with HPV 31 (9.3%), 3 cases with HPV 35 (7.0%), 1 case with HPV 18 (2.3%) and 1 case with HPV 58 (2.3%). The HPV types were divided into 3 groups, HPV 16, HPV 33 and other HPV types (HPV 18, 31, 35, 58), and comparisons and examinations were performed among the 3 groups. Although the rates of tumor reduction and operation accomplishment after 3 courses of BOAI showed no significant differences among the 3 groups, there were significant differences in the survival rates. The survival rate of advanced uterine cervical cancer patients with HPV 33 infection was the highest, followed by that of patients with HPV 16 infection. The survival rates of patients with the other types of HPV infection were the worst among the 3 groups and significantly lower than those of patients with HPV 16 or HPV 33 infection. The differences in the curative effect after BOAI may depend on the different characters of the HPV types.

Evidence for the association of human papillomavirus infection and cutaneous squamous cell carcinoma in immunocompetent individuals.

The aim of our study was to evaluate human papillomavirus (HPV) infection as a risk factor for cutaneous squamous cell carcinoma (SCC) in immunocompetent individuals. Hospital-based case-control study. Referral center for dermatologic diseases for central and southern Italy. Consecutive patients with histologically confirmed cutaneous SCC (n = 46) and control subjects (n = 84) chosen by frequency matching (age and sex) among patients admitted with unrelated diseases. Infection with epidermodysplasia verruciformis-related HPV types, blindly assessed by serologic testing (viruslike particle enzyme-linked immunosorbent assay). Information was obtained on known potentially confounding risk factors (family history, history and signs of sun exposure, and pigmentary traits) and on history of HPV-related lesions and diseases, assessed by interview and examination by a dermatologist. Positive serologic findings for HPV type 8 were associated with SCC (odds ratio, 3.2; 95% confidence interval, 1.3-7.9) independently of other risk factors, whereas positive serologic findings for HPV type 15 were negatively associated with SCC (odds ratio, 0.4; 95% confidence interval, 0.2-0.9). Other variables significantly associated with the tumor were family history of skin cancer, professional or recreational sun exposure, light eye color, high number of solar keratoses and seborrheic keratoses on the body surface, and residency in radon-emitting buildings. Positive serologic findings for HPV type 8 are associated with SCC occurrence in immunocompetent individuals. Viral infection could act as a cofactor in the tumor development, along with genetic predisposition, solar radiation, and other environmental exposures. If confirmed, these findings could open new perspectives for treatment and prevention of SCC.

Association of human papillomavirus infections with cutaneous tumors in immunosuppressed patients

Abstract Besides immunosuppression and UV radiation, human papillomavirus (HPV) infection was also suggested to be involved in the development of non-melanoma skin cancer, the most common malignancy after transplantation. In this study we used a comprehensive PCR assay to analyze the prevalence of individual HPV types in different skin lesions from transplant and non-transplant patients. HPV DNA was detected more frequently in squamous cell carcinomas (SCCs) of transplant recipients (75%) than the same lesion was in non-immunosuppressed patients (47%). Similar HPV prevalences were found in cutaneous warts (91% vs 94%), pre-malignant skin tumors (38% vs 36%), and normal skin specimens (17% vs 16%) of both patient populations. Overall, more than 40 different HPV types were identified. HPV types 5 and 8 were found more frequently in SCCs (26%) than in pre-cancerous (5%) or benign lesions (1%). All HPV 5- and HPV 8-positive SCCs were from immunosuppressed patients, indicating that infection with HPV 5 and HPV 8 may present an increased risk of SCC development in these patients.

Association of human papillomavirus infections with cutaneous tumors in immunosuppressed patients.

Besides immunosuppression and UV radiation, human papillomavirus (HPV) infection was also suggested to be involved in the development of non-melanoma skin cancer, the most common malignancy after transplantation. In this study we used a comprehensive PCR assay to analyze the prevalence of individual HPV types in different skin lesions from transplant and non-transplant patients. HPV DNA was detected more frequently in squamous cell carcinomas (SCCs) of transplant recipients (75%) than the same lesion was in non-immunosuppressed patients (47%). Similar HPV prevalences were found in cutaneous warts (91% vs 94%), pre-malignant skin tumors (38% vs 36%), and normal skin specimens (17% vs 16%) of both patient populations. Overall, more than 40 different HPV types were identified. HPV types 5 and 8 were found more frequently in SCCs (26%) than in pre-cancerous (5%) or benign lesions (1%). All HPV 5- and HPV 8-positive SCCs were from immunosuppressed patients, indicating that infection with HPV 5 and HPV 8 may present an increased risk of SCC development in these patients.

Association of human papillomavirus infection with carcinoma of the cervix uteri and its precursor lesions: theoretical and practical implications.

Human papillomaviruses (HPVs) are the major aetiological agents of cervical carcinoma. In this review, epidemiological and molecular data are combined to present a model for HPV-induced cervical carcinogenesis. The impact of current knowledge regarding diagnostic and therapeutic approaches is shown, i.e. the use of HPV tests in cervical cancer screening, in the management of atypical smears of uncertain diagnosis and in smears indicative of mild dysplasias, as well as in follow-up examinations during and after therapy. In addition, the value of the two most frequently used HPV detection systems, polymerase-chain reaction (PCR) and hybrid capture (HC) analysis, is discussed.

Association of human papillomavirus infection and disease with magnitude of human immunodeficiency virus type 1 (HIV-1) RNA plasma level among women with HIV-1 infection.

Ninety-three women with human immunodeficiency virus type 1 (HIV-1) infection were enrolled in a cross-sectional study to evaluate the relationship between plasma HIV-1 RNA levels and coincident cervical infection and disease caused by human papillomaviruses (HPVs). HIV-1 RNA plasma levels of >10,000 copies/mL were highly associated with the presence in cervical specimens of HPV DNA of oncogenic (high risk) virus genotypes (P=.006; relative risk, 2.57). In addition, similar HIV-1 RNA plasma levels were associated with abnormal Pap smears (P=.01; relative risk, 2.11). In this study, 81% of women with high-risk HPV cervical infection had abnormal Pap smears. Measurement of HIV-1 RNA plasma levels may help to identify a subgroup of HIV-1-infected women at increased risk for cervical HPV infection and disease.

Association of Human Papillomavirus Infection with HIV-1 RNA Plasma Levels in HIV-Infected Women

Lee, Bang-Ning1; Tortolero, Guillermo1; Helfgott, Andrew2; Eriksen, Nancy2; Hammill, Hunter1; Rabel, Karen1; Mitchell, Mitchele Follen; Shearer, William3; Reuben, James1 Author Information

Human papillomavirus DNA in cervical intraepithelial neoplasia detected by in situ hybridisation

Human papillomavirus (HPV) infection was investigated by in situ hybridisation in histological sections from 38 women with abnormal Papanicolaou smears. 13 patients had condylomatous lesions without atypia, 15 cervical intraepithelial neoplasia (CIN) I, 4 CIN II, 3 CIN III and 2 carcinoma in situ (CIS). HPV DNA was detected in 29 cases (78%) (1 specimen was technically inadequate). HPV 16 and 18, and 31, 33 and 35 were both present (67%) in CIN III. HPV 6 and 11 were more frequent in CIN I (56%) and in condylomatous lesions (38%). 31% of the condylomatous lesions without atypia contained HPV 31, 33, and 35 and 31% of those with CIN I were infected with HPV 16 and 18. These data confirm the frequent association of HPV infection with cervical cancer and CIN, and indicate that in situ hybridisation can identify patients with specific types of HPV infection at risk for cervical cancer.

Association of human papillomavirus infection and vulvar intraepithelial neoplasia: A morphological and immunohistochemical study of 30 cases

Thirty cases of vulvar intraepithelial neoplasia (VIN) were analyzed in order to determine the frequency of association with human papillomavirus (HPV) infection, and the relationship between this association and patient's age, extent of vulvar lesions, and coexistence with cervicovaginal neoplasia. The presence of condyloma or moderate to marked koilocytosis, now considered as morphological evidence of HPV infection, was observed in 66.6% of our cases. A search for HPV antigens, using the peroxidase-antiperoxidase (PAP) method, was performed in 13 selected cases, and positive staining was detected in 3 of them. The presence of HPV infection correlates with a mean age of 48.8 years, 50% of multicentricity of VIN and coexistence with cervical neoplasia in 30% of the cases, as opposed to a mean age of 55.5 years, 10% of multicentricity of VIN and absence of cervical neoplasia in patients without HPV infection. The demonstration of multiple foci of early stromal invasion in a 43-year-old woman, with multicentric VIN lesions associated with HPV infection, indicates that, even in the presence of such clinicopathological features, the risk of developing stromal invasion should be considered. Considerations are made in relation with the presence of HPV antigen in morphological normal epithelium adjacent to the lesion. Therapeutic implications were also investigated.