Prevalence of human papillomavirus in saliva of women with HPV genital lesions

Background

The human papilloma viruses (HPVs) are DNA viruses associated with benign and malignant lesions of skin and mucous membranes. The HPVs has been implicated as the cause of virtually all cervical cancers worldwide but studies showed that these viruses can cause numerous cancers in several tissues including Oral Squamous Cell Carcinoma (OSCC). At least 90 % of HPV-positive OSCCs are associated with high-risk (or oncogenic) HPV-16 and oral infection confers an approximate 50-fold increase in risk for HPV-positive OSCC. HPV-positive OSCCs are associated with sexual behaviors in contrast to HPV-negative OSCCs that are associated with chronic tobacco and alcohol use. The aim of this study was to estimate the prevalence of HPV-DNA in saliva samples collected from women in which it has been previously established the HPV infection of the cervix with relative genotyping and, then, to study the possible correlation.

Methods

Saliva samples were collected from 100 women with HPV cervical lesions, aged between 22 and 52 years old, and 25 healthy women with normal cytology (control group), aged between 20 and 49 years old. PCR assay was used to detect HPV DNA.

Results

The prevalence of oral HPV infection in saliva samples was 24 % in women with HPV cervical lesions while in the control group was 8 %. It has been demonstrated a strong association between high grade squamous intraepithelial lesion and oral infection due to HPV16 and 18, that are the most frequently detected HPV genotypes.

Conclusion

This study shows that patients with genital HPV infection are at risk for oral infection and, consequently, for the development of OSCC.

     

Variants of human papillomaviruses 16 (HPV16) in Uigur women in Xinjiang,China

Background

Persistent infection of high-risk human papillomaviruses 16 (HPV16) has been considered as the leading cause of cervical cancer. In this study we assessed HPV16 sequence variation and genetic diversity of HPV16 variants in cervical cancer in Uigur women in Xinjiang, China. We analyzed the nucleotide sequences of the open reading frames of E6 and E7, and part of the open reading frames of L1 of HPV16 in Uigur women.

Methods

Biopsies of histologically confirmed HPV16 infections with cervical cancer were obtained from 43 Uigur women in Xinjiang, China. E6, E7 and L1 genes of HPV16 of all samples were amplified and sequenced; the sequences were used in phylogenetic analysis of HPV16 variants.

Results

Our analysis revealed nine nucleotide changes in E6 (five changes), E7 (one change) and L1 (three changes) gene. The most frequently observed variations were T350G (79.1 %). One variation T295G (D64E) at E6 were detected in 6 cases (KT959536, KT959542, KT959546, KT959550, KT959553, KT959558). Deletion (464Asp) along with insertion (448Ser) were observed in L1 (100 %). Most variants were European lineage (97.7 %); only one belongs to Asia variants with common T178G (D25E) in E6 and A647G (N29S) in E7.

Conclusion

The most prevalent HPV16 variants in the Uigur women we studied were of the European lineage. Our results indicate that HPV16 European lineage may serve as a harmful factor associated with the development and progression of cervical cancer.

     

Human papillomavirus genotypes and HPV-16 variants distribution among Tunisian women with normal cytology and squamous intraepithelial lesions

Background

Little is known about the epidemiological characteristics of papillomavirus (HPV) infection among North African countries. Herein, we conducted a molecular epidemiological study to investigate prevalence of HPV type and HPV-16 variants among cervical-screened unvaccinated Tunisian women.

Methods

Cross-sectional study was performed on 494 Tunisian women visiting Women’s Healthcare Centers. HPV-DNA detection was carried out on cervical samples using real-time polymerase chain reaction. HPV genotyping and HPV-16 variants were characterized by direct sequencing of L1 viral capsid gene.

Results

The overall HPV prevalence was 34% (95% CI: 30–38%) with significantly higher prevalence among women with squamous intraepithelial lesions (SIL) than those with no intraepithelial lesions (NIL) 84% (95% CI: 76–92%) and 24.5% (95% CI: 20–29%) respectively. The distribution of HPV prevalence according to women’s age shows a U-shaped curve and the highest HPV prevalence rates were observed among the youngest (≤25 years; 51.2%, 95% CI: 37–67%) and the oldest women (>55 years; 41.7%, 95% The HPV-16 prevalence was 32.8% (95% CI: 22–45%) among women with SIL and 9.2% (95% CI: 6–12%) among women with NIL. Whereas, the HPV-18 prevalence was 1.3% (95% CI: 0–5%) among women with SIL and 0.3% (95% CI: 0–1%) among women with NIL. Among HPV-16 positive women, European lineage (E) was identified as the predominant HPV-16 variant (85.7%, 95% CI: 76–95%). The frequency of E variant was lower among SIL than among NIL women (81%, 95% CI: 64–99%, and 88%, 95% CI: 77–100%, respectively). Conversely, the African-2 variant frequency was higher among SIL than among NIL women (18%, 95% CI: 1–36% and 6%, 95% CI: 2–14%, respectively). In multivariate analysis, young age was the only risk factor that is independently associated with HPV infection. Moreover, HPV infection and menopause were both found to be independently associated with SIL and HSIL.

Conclusion

HPV DNA testing should be proposed to young and menopausal Tunisian women. Considering HPV prevalence, only 13% of the Tunisian women could be protected by the bivalent HPV vaccine. These results may be helpful for designing an adapted HPV testing and vaccination program in Tunisia.

     

Molecular analysis of human Papillomavirus detected among women positive for cervical lesions by visual inspection with acetic acid/Lugol’s iodine (VIA/VILI) in Libreville,Gabon

Background

The human papillomavirus (HPV) is the causative agent of cervical cancer, which is the leading cancer-related cause of death for women in Sub-Saharan Africa. In 2013, the Gabonese Ministry of Health and the Sylvia Bongo Ondimba Foundation implemented cervical cancer screening programs based on the detection of cancerous lesions by visual inspection with acetic acid and/or Lugol’s iodine (VIA/VILI). This pilot study was set up to determine the HPV profile and analyze the nucleotide sequence variation of HPV16 circulating in patients with cervical abnormalities detected by VIA/VILI testing.

Methods

The cervical abnormalities observed upon VIA/VILI were confirmed by liquid-based cytology for all tested women. Nested PCR using the MY09/11 and GP5+/6+ primer sets was used to detect HPVs present in the extracted DNA. HPV genotypes were determined after sequencing of amplicons based on a high-throughput sequencing approach. For isolates of the HPV16 genotype, the E6 gene and the long control region (LCR) were directly sequenced using Sanger method.

Results

The study included 87 women who showed a positive VIA/VILI result. Cervical abnormalities were found in 40.23 % of women and 40 % were classified as high-grade lesions. The HPV detection rate was 82.9 % among women with abnormal cytology. Among all the identified high-risk HPV genotypes, HPV16, 18 and 33 were the most frequent. Multiple HPV infections were observed in 42.31 % of HPV-infected women. Analysis of the HPV16 sequence variation in the E6 gene and in the LCR showed that 85.3 and 14.7 % belonged to the African and European lineages, respectively. Among the African branch variants, Af2 was the most frequently identified in this study.

Conclusion

This study offers the first report of the HPV detection rate and molecular epidemiology among Gabonese women with a positive result in a VIA/VILI screening test. Moreover, data on the HPV16 sequence variation confirm the predominance of African variants in high-grade lesions.

     

Cervical human papillomavirus prevalence and genotype distribution among hybrid capture 2 positive women 15 to 64 years of age in the Gurage zone,rural Ethiopia

Background

Human papillomavirus (HPV) infection is a prerequisite of cervical cancer, the leading cause of cancer mortality in Ethiopian women today. Data on Ethiopian cervical HPV prevalence and genotype distribution are rare, but essential as pre-vaccine baseline data to monitor changes after initiating HPV vaccination. The objectives of this study were to assess the cervical HPV prevalence, genotype distribution and associated correlates among female hospital outpatients in rural Ethiopia.

Methods

We examined a consecutive sample of 537 women 15–64 years of age in rural Ethiopia between November and December 2006. Screening for low risk (LR) and high-risk (HR) cervical HPV infection was performed and HR positive samples were genotyped with a GP5+/6?+?? and SPF10-primer based system.

Results

The age-standardized prevalence of HPV, HPV HR and HPV LR infection was 17.3% (95% CI 14.1-20.5), 15.8% (95% CI 12.7-18.9) and 3.9% (95% CI 2.3-5.6), respectively. Among HC2 HPV HR positive infections (n?=?86), the most common genotype was HPV 16 (24.4%), followed by 52 (11.6%), 56 (10.5%) and 31 (10.5%). Non-married relationship and widowhood, increasing number of lifetime sexual partners, human immunodeficiency virus infection and non-traditional housing type, but not age, were significantly associated with HR HPV infection.

Conclusions

These results on cervical HPV prevalence and genotype distribution may serve as baseline data in evaluating the impact of future HPV vaccination programmes in rural Ethiopia.

     

Detection of human papillomavirus DNA in tumors from Rwandese breast cancer patients

Background

During the last decades, a great interest was given to viral etiology of breast cancer. Indeed, due to recent technical improvements and some encouraging new results, it has been a resurgence of interest in the possibility that a substantial proportion of human breast cancers may be caused by viral infections. High-risk genotypes of human papillomavirus (HPV) have been found in breast cancer cases. In the present study, we aimed to assess the presence of HPV DNA in breast cancer cases from Rwanda and to evaluate the association between HPV infection and clinico-pathological features.

Methods

Therefore, a total of 47 archived formalin-fixed paraffin-embedded biopsies were collected and complete information was recorded. HPV detection and genotyping were done by PCR amplification and DNA sequencing.

Results

Overall, HPV DNA was found in 46.81% of cases, HPV16 being the most prevalent subtype (77.27%) followed by HPV33 (13.64%) and HPV31 (9.09%). Comparison of HPV with clinico-pathological features showed no significant difference between HPV infection and breast localization, histological subtype, clinical stage, tumor grade, and intrinsic molecular subtypes.

Conclusions

These findings provide evidence of high prevalence of high-risk HPV in Rwandese patients with breast cancer and suggest that high-risk HPV infections could be a risk factor associated with human breast cancer development.

     

HPV16 variant lineage,clinical stage,and survival in women with invasive cervical cancer

Background

HPV16 variants are associated with different risks for development of CIN3 and invasive cancer, although all are carcinogenic. The relationship of HPV 16 variants to cancer survival has not been studied.

Methods

155 HPV16-positive cervical cancers were categorized according to European and non-European variant patterns by DNA sequencing of the E6 open reading frame. Clinico-pathologic parameters and clinical outcome were collected by chart review and death registry data.

Results

Of the 155 women (mean age 44.7 years; median follow-up 26.7 months), 85.2% harbored European variants while 14.8% had non-European sequences. HPV16 variants differed by histologic cell type (p = 0.03) and stage (1 vs. 2+; p = 0.03). Overall, 107 women (68.0%) were alive with no evidence of cancer, 42 (27.1%) died from cervical cancer, 2 (1.3%) were alive with cervical cancer, and 4 (2.6%) died of other causes. Death due to cervical cancer was associated with European variant status (p < 0.01). While 31% of women harboring tumors with European variants died from cervical cancer during follow-up, only 1 of 23 (4.4%) non-European cases died of cancer. The better survival for non-European cases was partly mediated by lower stage at diagnosis.

Conclusions

Overall, invasive cervical cancers with non-European variants showed a less aggressive behavior than those with European variants. These findings should be replicated in a population with more non-European cases.

     

Human papillomavirus genotypes among women with or without HIV infection: an epidemiological study of Moroccan women from the Souss area

Background

Data on Human PapillomaVirus (HPV) infection are scarce in Morocco. The objective of the study was to determine the prevalence of HPV and cervical cytology abnormalities in women from the Souss area, Morocco.

Methods

Two hundred and thirty two women who attended the Hassan II hospital (Agadir, Morocco) were recruited in this study. Socio-economic data, sexual activity, reproductive life, history of Pap smear, smoking and HIV status were recorded. Cervical samples were taken using an Ayre spatula. Cytology was reported using the Bethesda system. HPVs were first detected by MY09/11 consensus PCR and then genotyped with INNO-LiPA^® assay. Data were analyzed using the logistic regression model.

Results

The median age of women was 42 years (18–76 years). HIV prevalence was 36.2 %. Any HPV type prevalence was 23.7 % in the study population, lower in HIV-negative women (13.3 %) than in HIV-positive women (39.3 %). HPV16 was the most prevalent type (6.5 %), followed by HPV53 and HPV74 (3.4 % each). Most women had normal cervical smears (82 %), the remaining were diagnosed with LGSIL (13 %) and HGSIL (5 %). HPV was detected in 17.4 % of normal smears, 43.4 % of LGSIL and 75 % of HGSIL. HIV status was the most powerful predictor of high risk (hr) and probable hr (phr) HPV infection (odds ratio 4.16, 95 % confidence interval 1.87–9.24, p?=?0.0005) followed by abnormal cytology (OR 3.98, 95 % CI 1.39–11.40, p?=?0.01), independently of socio-demographic and behavioral risk factors.

Conclusions

In a Moroccan hospital based-population of the Souss area, HPV infections are frequently detected. In addition, high prevalence of hr and phrHPVs and precancerous lesions among HIV-positive women is likely associated with an increased risk of cervical cancer. This highlights the need for HPV and cervical cancer prevention campaigns in Morocco.

     

HPV-16 infection modifies overall survival of Puerto Rican HNSCC patients

Background

HPV-16 modifies the overall survival (OS) of patients with oropharyngeal cancer (OPSCC). HPV-16 has been established as risk factor for OPSCC, but HPV-16 infection may also reside in the larynx and oral cavity. We evaluated HPV-16 status on OS of Head and Neck Squamous Cell Carcinoma (HNSCC) patients.

Methods

HPV-16 infection was confirmed by amplification of E6 and E7 viral oncogenes through PCR assay and E6 IHC in 185 HNSCC samples. Associations between HPV-16 status and clinicopathological parameters were performed using Fisher’s exact test and x². Survival analysis was completed using Kaplan-Meier estimator and multivariate Cox regression analysis.

Results

OS of HPV-16 positive patients was longer compared to HPV-16 negative patients (P?=?0.002). HPV-16 positive tumors of the larynx (LSCC) and pharynx (PSCC) showed improved OS compared to HPV-16 negative tumors. Also, HPV-16 positive patients exposed to radiotherapy presented a better survival.

Conclusions

HPV-16 status has a positive prognostic value in HNSCC. Addition of HPV-16 status to the TNM staging can provide better assessment in prognosis and guide treatment for HNSCC patients.

     

Prevalence of HPV infection in hypopharyngeal and laryngeal squamous cell carcinoma at Thailand's largest tertiary referral center

Background

Following the well-established relationship between human papillomavirus (HPV) and cervical carcinoma, the carcinogenicity of this virus has also been confirmed in subsets of head and neck carcinoma (HNCA), but mainly in the oropharynx. Other subsites of HNCA with less known association to HPV have never been studied in Thailand. Accordingly, the aim of this study was to investigate the prevalence of HPV DNA in hypopharyngeal and laryngeal squamous cell carcinoma in Thai population.

Methods

This cross-sectional study included hypopharyngeal and laryngeal squamous cell carcinoma patients diagnosed and treated at the Department of Otorhinolaryngology, Siriraj Hospital during the September 2011–December 2013 study period. Presence of HPV genome was confirmed by polymerase chain reaction from pathologically-confirmed fresh specimens. Demographic data and risk factors of HPV infection were evaluated.

Results

Eighty patients were included, and 95% of those were male. Only one patient was noted with positive HPV-62 serotype. Most patients consumed tobacco and/or alcohol. Five patients had no risk factors for cancer development. Risk of HPV infection was evaluated by self-reporting questionnaire. The mean age of sexual debut was 20.17 years. Forty-eight patients had multiple sexual partners. Sixteen and seven patients had history of sexually transmitted disease infection and habitual oral sex contact, respectively.

Conclusion

There was no oncogenic HPV DNA detected within pathologic specimens of laryngeal and hypopharyngeal cancers in this study. Compared to rates reported from developed countries, the prevalence of HPV-related HNCA in Thailand is very low.

     

Prevalence of “unclassified” HPV genotypes among women with abnormal cytology

Background

High risk human papillomaviruses (HPVs) have been unequivocally recognised as the necessary cause of squamous intraepithelial lesions (SIL) and invasive carcinoma of the cervix. The distribution and the role of unclassified risk HPV genotypes in cervical neoplasia has not been fully elucidated.

Methods

Liquid-based cytological samples were collected from 337 women referred for colposcopy following an abnormal cytological diagnosis. HPV DNA was detected by broad-spectrum PCR and genotypes identified by nucleotide sequencing analysis and reverse line blot (RLB).

Results

The overall frequency of HPV infection was 36.5% (35 out of 96) in samples negative for intraepithelial lesions or malignancy (NILM), 80% (181 out of 226) in low grade SIL and 93.3% (14 out of 15) in high grade SIL (P?<?0.001). Thirty-five different genotypes were identified among the 230 HPV-positive cases. The Group 1 oncogenic viruses (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59) were found in 21.9, 46.5, and 86.7% of NILM, low grade SIL and high grade SIL, respectively. The Group 2A, including the probably oncogenic virus HPV68, was found in 1 and 0.8% of NILM and low grade SIL, respectively. The Group 2b possibly oncogenic HPVs (HPV34, 53, 66, 67, 70, 73, 82 and 85) were found in 4.2, 21.7 and 26.7% of NILM, low grade SIL and high grade SIL, respectively. The unclassified viruses (HPV12, 42, 54, 55, 61, 62, 81, 83, 84, 89, 90, 91) were detected in 8.3 and 14.6% of NILM and low grade SIL, respectively, and never in high grade SIL.

Conclusions

Group 1 HPVs were mainly prevalent in high grade SIL and low grade SIL while Group 2B were equally distributed among the two groups. The dominant frequency of unclassified HPVs in low grade SIL and NILM and their rarity in high grade SIL suggests their marginal role in cervical neoplasia of the studied population.

     

Prevalence of human papillomavirus among Wenzhou women diagnosed with cervical intraepithelial neoplasia and cervical cancer

Background

Human papillomavirus (HPV) is associated with an increased risk of cervical cancer. Using a vaccine to prevent HPV infections could be a cost-effective strategy to decrease the incidence of cervical cancer. Learning about the characteristics of CIN patients with HPV infection in Wenzhou is a key step in guiding the use of HPV vaccines and screening for cervical cancer.

Methods

We undertook a retrospective analysis including 2612 women who were treated in the Department of Gynecology and Obstetrics from Jan 2016 to Nov 2017. All of the patients were examined by HPV testing and histology.

Results

The prevalence of HR-HPV among women with cervical intraepithelial lesions aged 65–69?years (38.8%) was significantly higher than that of the other age groups. The percentage of patients diagnosed with HPV-positive HSIL progressively increased with age to a maximum of 18.0% in the group of 40 to 44?years of age. HPV 16, 52, and 58 were the three most dominant genotypes among these women, and single infections (950, 73.3%) were more common than multiple infections (346, 26.7%). Compared to cervicitis, the odds ratios (ORs) for LSIL associated with HPV 33, 52, 16 and HPV 58 infection were 5.98, 3.91, 3.65, 3.65, and 3.188, respectively; for HSIL associated with HPV 16, 33, 58 and HPV 31 were 9.30, 7.68, 5.97, and 4.21, respectively. In LSIL, the frequencies of HR-HPV 52,16,58,18 were 19.3,18.2,10.9, and 7.8%, respectively.

Conclusion

Our study provides important data about the HPV genotype distribution and its correlation with cervical intraepithelial lesions in the Wenzhou population.

     

Variability of high risk HPV genotypes among HIV infected women in Mwanza,Tanzania- the need for evaluation of current vaccine effectiveness in developing countries

Background

High risk (HR) human papilloma Virus (HPV) genotypes have been associated with cervical cancer. In Tanzania there is a limited data on the epidemiology of HPV and genotypes distribution among HIV infected women. Here we document varieties of HPV genotypes associated with cervical squamous intraepithelial lesions (SIL) among HIV- infected women at Bugando Medical Centre, Mwanza-Tanzania.

Methods

A cross sectional hospital based study involving HIV infected women was conducted between August and October, 2014. Exfoliated cells from ectocervix and endocervix were collected using cytobrush. HPV genotypes were detected using polymerase chain reaction (PCR) followed by sequencing using specific primers targeting broad range of HPV types. Cytology was done to establish squamous intraepithelial lesions. Log binomial regression analysis was done to establish risk ratios (RR) associated with HPV infection using STATA version 11.

Results

A total of 255 HIV infected women with mean age 39.2?±?9.1 years were enrolled in the study. HPV DNA was detected in 138/255 (54.1 %, 95 % CI: 47-60) of HIV infected women. Twenty six genotypes were detected in various combinations; of these 17(65.3 %) were of HR genotypes. HR genotypes were detected in 124(48.6 %) of HIV infected women. Common HR genotypes detected were HPV-52(26), HPV-58(21), HPV-35(20) and HPV-16(14). The risk of being HPV positive was significantly higher among women with CD4 counts <100 (RR: 1.20, 95 % CI: 1.05-1.35, P?=?0.006) and women with SIL (RR: 1.37, 95 % CI: 1.11-1.68, P?=?0.005)

Conclusion

Significant proportion of HIV infected women with low CD4 counts have various grades of cervical SIL associated with varieties of uncommon HR genotypes. There is a need to evaluate the effectiveness of the current vaccine in preventing cervical cancer in developing countries where HIV is endemic.

     

Single and multiple high-risk and low-risk Human Papillomavirus association with cervical lesions of 11,224 women in Jakarta

Purpose

We sought to evaluate prevalence, age-adjusted distribution, and impact of single and multiple high- and low-risk human papillomavirus (HPV) subtypes and their associations with cervical lesions.

Methods

Data were extracted from 11,224 women who underwent routine screening of HPV genotyping and liquid-based cytology co-testing. Fifteen high-risk (HR) and six low-risk (LR) HPV types were genotyped.

Results

Overall HPV prevalence was 10.7 %, and young women (under 21 years old) harbored highest HPV infection rate (40.38 %). The rate declined in old women 9.49 % (age 30–49) and 6.89 % (age 50 and above). Normal cytology had lowest HPV (5.66 %) compared to low-grade (60.49 %), high-grade (71.96 %) squamous intraepithelial lesions (LSIL and HSIL) and squamous cell carcinoma SCC (86.9 %). LR HPV subtypes were absent in SCC and were consistently lower than HR HPV in LSIL (6.74 vs. 33.54 %) and HSIL (2.12 vs. 51.32 %). Multiple HPV infection was more frequent in young women under 30 years old (10 %) than older women (2 %) and in LSIL (20.2 %), HSIL (18.5 %) than SCC (4.4 %). HR HPV 52, 16, 18, and 58 were the most frequent subtypes in normal, LSIL, and HSIL. Greater or equal proportion of HPV 16, 18, 45, and 52 was found in SCC compared to normal cytology (SCC/normal ratios 4.8, 1.2, 1.6, and 1.7). While important in LSIL and HSIL, HPV58 was not detected in SCC.

Conclusion

Taken together, identification of these HPV types, especially HPV 16, 18, 45, and 52, and their associated cervical lesions may improve cervical cancer preventive strategies in Indonesia.

     

Humane Papillomaviren und Zervixkarzinom

Background

Cervical cancer is the fourth most commonly occurring malignancy in women worldwide. Extrapolations by the Robert Koch Institute on the basis of cancer registry data in Germany showed that approximately 4600 women were diagnosed with cervical cancer in 2012.

Results

The cause of cervical cancer is a long-lasting infection with certain types of human papillomavirus (HPV) and without these viruses almost no cases of cervical cancer occur. A differentiation is made between types of virus that cause mainly warts (so-called low-risk types) and those that can trigger cancer (high-risk types). The first group includes HPV 6 and 11 and the second group includes types HPV 16 and 18, which are responsible for approximately 70?% of all cervical cancer cases. Since 2006 two vaccines have been available against the two types with the highest risk (HPV 16 and 18) and since 2015 there is a vaccine on the market that protects against five additional high-risk types (HPV 31, 33, 45, 52 and 58). This new nonavalent vaccine can prevent roughly 90?% of cervical cancers.

Conclusion

Regular participation in cervical cancer screening programs is still recommended.

     

Inconclusive role of human papillomavirus infection in breast cancer

Background

Epidemiological studies have examined the association between human papillomavirus (HPV) and breast cancer, but the findings are inconclusive. This study aimed to detect the prevalence of HPV in breast cancer tissue in patients from northeastern China and define the association between HPV and breast cancer using meta-analysis.

Methods

Polymerase chain reaction (PCR) was used to test cutaneous or mucosal HPV DNA sequence in 77 breast cancer samples and 77 corresponding adjacent normal tissues. The prevalence of HPV in breast cancer was estimated by pooling data from 38 studies. A meta-analysis of 16 case–control studies was conducted to investigate the association between HPV and breast cancer.

Results

We did not find HPV DNA sequence in any of the 154 tissue specimens we tested. However, our meta-analysis revealed a HPV prevalence of 30.30 % (95 % confidence interval [CI]?=?22.30–38.40 %) among breast cancer cases; most of these involved high-risk HPV types (35.50 %, 95 % CI?=?25.00–46.10 %). HPV prevalence in breast cancer varied by geographic region, publication period, and PCR detection method. An increased risk of breast cancer was observed in association with exposure to HPV (odds ratio [OR]?=?3.24, 95 % CI?=?1.59–6.57), which was influenced by geographic region, HPV DNA source, PCR primer used, and publication period.

Conclusions

HPV, especially high-risk HPV types, may be associated with an increased risk of breast cancer, and this association varies dramatically among geographic regions.

     

HPV16 integration probably contributes to cervical oncogenesis through interrupting tumor suppressor genes and inducing chromosome instability

Background

The integration of human papilloma virus (HPV) into host genome is one of the critical steps that lead to the progression of precancerous lesion into cancer. However, the mechanisms and consequences of such integration events are poorly understood. This study aims to explore those questions by studying high risk HPV16 integration in women with cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (SCC).

Methods

Specifically, HPV integration status of 13 HPV16-infected patients were investigated by ligation-mediated PCR (DIPS-PCR) followed by DNA sequencing.

Results

In total, 8 HPV16 integration sites were identified inside or around genes associated with cancer development. In particular, the well-studied tumor suppressor genes SCAI was found to be integrated by HPV16, which would likely disrupt its expression and therefore facilitate the migration of tumor. On top of that, we observed several cases of chromosome translocation events coincide with HPV integration, which suggests the existence of chromosome instability. Additionally, short overlapping sequences were observed between viral derived and host derived fragments in viral-cellular junctions, indicating that integration was mediated by micro homology-mediated DNA repair pathway.

Conclusions

Overall, our study suggests a model in which HPV16 might contribute to oncogenesis not only by disrupting tumor suppressor genes, but also by inducing chromosome instability.

     

Human papillomavirus,high-grade intraepithelial neoplasia and killer immunoglogulin-like receptors: a Western Australian cohort study

Background

Human papillomavirus (HPV) is the causative agent in cervical cancer and HPV genotypes 16 and 18 cause the majority of these cancers. Natural killer (NK) cells destroy virally infected and tumour cells via killer immunoglobulin-like receptors (KIR) that recognize decreased MHC class I expression. These NK cells may contribute to clearance of HPV infected and/or dysplastic cells, however since KIR controls NK cell activity, KIR gene variation may determine outcome of infection.

Methods

KIR gene frequencies were compared between 147 patients with a history of high-grade cervical intraepithelial neoplasia (CIN) and a control population of 187, to determine if any KIR genes are associated with high-grade CIN. In addition a comparison was also made between cases of high grade CIN derived from 30 patients infected with HPV 16/18 and 29 patients infected with non-16/18 HPV to determine if KIR variation contributes to the disproportional carcinogenesis derived from HPV 16/18 infection.

Results

High-grade CIN was weakly associated with the absence of KIR2DL2 and KIR2DS2 (p?=?0.046 and 0.049 respectively, OR 0.6; 95% CI 0.4 – 0.9) but this association was lost after correction for multi-gene statistical analysis. No difference in KIR gene frequencies was found between high-grade CIN caused by HPV 16/18 and non-16/18.

Conclusion

No strong association between KIR genes, high-grade CIN and HPV genotype was found in the Western Australian population.

     

Human papillomavirus (HPV) and Epstein-Barr virus (EBV) in keratinizing versus non- keratinizing squamous cell carcinoma of the oropharynx

Background

Oral and oropharyngeal squamous cell carcinomas (OSCC and OPSCC) represent the majority of head and neck squamous cell carcinomas (HNSCC). Human papillomavirus (HPV) is an important etiologic factor together with Epstein-Barr virus (EBV). Little is known on the prevalence of major herpesviruses [EBV, cytomegalovirus (CMV) and HHV-6, ??7 and???8] in HNSCCs.

Methods

Fifty-one formalin-fixed paraffin-embedded (FFPE) tissue samples taken at surgery (40 oropharyngeal, 11 oral) were analyzed for 40 HPV genotypes (20 high-risk types), EBV, CMV, HHV-6, ??7 and???8 by quantitative PCR. Expression of the HPV-induced p16^INK4A protein was also investigated by immunohistochemistry (IHC).

Results

In SCC, the prevalence of EBV was significantly higher compared to that of HPV (EBV 51% vs. HPV 19.5%; P =?0.005). HPV infection was found in 25% of OPSCC and in none of the OSCC; conversely, higher prevalence of EBV was found in OSCC (72.7%). HPV and EBV co-infection was detected only in 4 (10%) OPSCC. CMV was detected in only two cases, whereas HHV-6, ??7 and???8 resulted negative. The prevalence of HPV but no EBV was associated with the non-keratinizing SCC type (NKSCC) compared to the keratinizing SCC type (KSCC)(HPV-DNA P <?0.005; EBV?=?0.054).

Conclusions

Single HPV or EBV positivity was higher in OSCC than in OPSCC. Other potentially oncogenic herpesvirus types were minimally or not represented.

     

Six years genotype distribution of Human Papillomavirus in Calabria Region,Southern Italy: a retrospective study

Background

Although analysis of the Human papillomavirus (HPV) genotype spread in a particular area has a crucial impact on public health and prevention programmes, there is a lack of epidemiological data regarding HPV in the Calabria region of Italy. We therefore update information on HPV age/genotype distribution by retrospectively analysing a cohort of women, with and without cervical lesions, living in Calabria, who underwent HPV DNA testing; moreover, we also evaluated HPV age/genotype distribution in a subset of patients with cervical lesions.

Methods

Cervical scrape specimens obtained from 9590 women (age range 20–75 years) from January 2010 to December 2015 were tested for HPV DNA. Viral types were genotyped by Linear Array HPV Genotyping® test (Roche, USA) at the Clinical Microbiology Operative Unit of six hospitals located in four provinces of the Calabria region.Cervical scrape specimens were also used to perform Pap smears for cytological analysis in a subset of 405 women; cytological classification of the samples was performed according to the Bethesda classification system.

Results

A total of 2974 women (31%) (C.I. 95% 30.09–31.94) were found to be HPV DNA positive for at least one (57.3%) or several (42.7%) HPV genotypes. Of single genotype HPV infections, 46.5% and 36.4 % were classed as high-risk (HR, Group 1) and low-risk (LR, Group 3) respectively, while 16.9% were classed as probably/possibly carcinogenic and 0.2% undetermined risk. Stratified by age, total HPV distribution, showed the highest prevalence within the range 30–39 years (37.2%), while single genotype infection distribution displayed a peak in women from the age range 20–29 years (37.5%). The most common high-risk HPV type was HPV 16 (19.1%), followed by HPV 31 (9.1%).

Conclusions

We provide epidemiological data on HPV age/genotype distribution in women living in the Calabria region with or without cytological abnormalities, further to the enhancement of HPV screening/prevention programmes for the local population.