Human papillomavirus detected in female breast carcinomas in Japan

To investigate the aetiological role of human papillomavirus (HPV) in breast cancer, we examined the presence, genotype, viral load, and physical status of HPV in 124 Japanese female patients with breast carcinoma. Human papillomavirus presence was examined by PCR using SPF10 primers, and primer sets targeting the E6 region of HPV-16, -18, and -33. The INNO-LiPA HPV genotyping kit was used to determine genotype. Human papillomavirus DNA was detected in 26 (21%) breast carcinomas. The most frequently detected HPV genotype was HPV-16 (92%), followed by HPV-6 (46%), HPV-18 (12%), and HPV-33 (4%). In 11 normal epithelium specimens adjacent to 11 HPV-16-positive carcinomas, 7 were HPV-16-positive. However, none of the normal breast tissue specimens adjacent to HPV-negative breast carcinomas were HPV-positive. The real-time PCR analysis suggested the presence of integrated form of viral DNA in all HPV-16-positive samples, and estimated viral load was low with a geometric mean of 5.4 copies per 10(4) cells. In conclusion, although HPV DNA was detected in 26 (21%) breast carcinomas and, in all HPV-16-positive cases, the HPV genome was considered integrated into the host genome, their low viral loads suggest it is unlikely that integrated HPV is aetiologically involved in the development of Japanese breast carcinomas that we examined.     

Human papillomavirus in lung carcinomas among three Latin American countries

The presence of human papillomavirus (HPV) genome in lung carcinomas has been reported worldwide but its frequency varies from country to country. We examined HPV genome in 36 lung carcinomas, consisting of 14 squamous cell carcinomas, 13 adenocarcinomas, and 9 small cell carcinomas, collected from Colombia, Mexico and Peru. PCR analysis using GP5+/GP6+ primers, combined with Southern blot hybridization, found the presence of HPV genome in 10 (28%) of 36 cases. This percentage is similar to the value of 22% reported by Syrj?nen, who conducted a meta-analysis of nearly 2500 lung carcinomas examined to date. Genotype analysis revealed that the most predominant genotype was HPV-16 (7 cases), followed by HPV-18 (2 cases) and HPV-33 (1 case). HPV-16 was more frequently found among female than male cases (P=0.008) but was not detected in any adenocarcinoma cases. On the other hand, HPV-18 and HPV-33 were detected only among male cases. These HPV genotypes were detected only in adenocarcinomas, and all the HPV genotypes detected in this histological type were HPV-18 or HPV-33. The frequency of HPV-16 positive cases among all the HPV positive cases differed in the sexes (P=0.033) and differed in the three histological types (P=0.017). The presence of HPV tended to be more frequent in well-differentiated tumors when squamous cell carcinomas and adenocarcinomas were combined. However, it was not statistically significant (P=0.093). Neither p16 nor p53 expression in carcinoma cells was related to the proportion of HPV-positive cases. In conclusion, high-risk HPV DNA was detected in 28% of lung carcinomas. The predisposition of HPV-16 to female cases and to non-adenomatous carcinomas warrants further investigation.     

High-risk human papillomavirus E7 oncoprotein detection in cervical squamous cell carcinoma.

PURPOSE: Persistent infections by high-risk human papillomavirus (HPV) types are the main etiologic factor for cervical cancer. The objective of this study was to evaluate whether high-risk E7 oncoprotein is adequate as a marker for the detection of cervical cancer. EXPERIMENTAL DESIGN: HPV typing was done in biopsies from 58 cervical carcinoma and 22 normal cervical squamous epithelia. The HPV-16 E7, HPV-18 E7, and HPV-45 E7 oncoprotein levels were monitored by immunohistochemistry and compared with those of p16(INK4a) and Ki67. RESULTS: Fifty-five (94.8%) tumors were high-risk HPV-DNA-positive (46 HPV-16, 2 HPV-16 and HPV-18, 4 HPV-18, 1 HPV-33, and 2 HPV-45). HPV-DNA could not be detected in three tumors (5.2%). High HPV E7 oncoprotein levels were shown in 57 cervical cancers (98.3%), without correlation between expression levels and tumor stages. CONCLUSION: This is the first study which systematically analyzes the levels of the major HPV oncoproteins in cervical carcinomas demonstrating that the high-risk HPV E7 proteins are regularly expressed in these cancers. This suggests that high-risk E7 oncoproteins are necessary for cervical cancers and apparently essential as tumor marker.     

Detection of High-Risk Human Papillomavirus Genotypes 16 and 18 in Head and Neck Squamous Cell Carcinomas in Jordan

Background: Recently, associations of the human papillomavirus (HPV) with head and neck cancer have become well established. Of particular concern, the severity and pathological outcomes of squamous cell carcinomas are remarkably affected by the genotypes of HPV present in such lesions. This study was conducted to investigate the occurrence of HPV genotypes, particularly high risk 16 and 18, among oral and laryngeal squamous cell carcinomas in Jordan. Methods: During the period of May 2015 to March 2016, we evaluated a total of 108 paraffin-embedded tissue samples, histologically confirmed as SCC, of both oral and laryngeal tumors for the presence of HPV DNA. DNA was extracted using a Zymogen commercial kit. HPV genotypes were detected by nested PCR using consensus primers followed by primer-specific PCR for HPV-16 and HPV-18 genotypes. The genotypes were confirmed by DNA sequencing methods. Results: Sixteen samples were positive for HPV DNA (14.8%) with higher rates in oral tumors compared to their laryngeal counterparts (20% and 6% respectively). The HPV-16 genotype predominated, being detected in 81.3% of the cases as a single infection and in 18.7% in combination with HPV-18. A significant association between the anatomical location and the HPV-16 genotype was observed (p < 0.05). In contrast, no significant associations could be established with tumor grade and gender or age. Conclusions: A relatively high rate of high-risk HPV genotypes, especially HPV 16, is evident in head and neck cancers SCCs in Jordan. Genotyping of HPV might be of considerable value for evaluation of progression.     

Simultaneous presence of herpes simplex and human papilloma virus sequences in human genital tumors

Herpes simplex virus (HSV) and human papillomavirus (HPV) sequences were analyzed in tumors of the female lower genital tract, by probing DNA from 13 intraepithelial and 30 invasive neoplastic lesions with radiolabelled HPV-16 and HPV-18 DNA as well as cloned fragments of HSV-2 DNA. Careful removal of stromal tissue from the pathological specimens allowed authentic tumor DNA to be processed. Normal genital tissue obtained from the patients and genital condylomata were included as internal controls. The presence of HPV-16 or 18 DNA was detected in 12/13 (92.3%) intraepithelial neoplasms and in 16/30 (53.3%) invasive carcinomas. No significant difference was detected in titer or frequency of antibodies to HPV group-specific antigen in sera from patients and controls. Hybridization to BgIII N fragment of HSV-2 DNA was detected in 4/13 (30.8%) intraepithelial neoplasms and 4/30 (13.3%) invasive carcinomas but in none of the control tissues. All the 8 samples harboring HSV-2 homologous sequences were also positive for HPV, supporting the hypothesis of a synergistic association between the 2 viruses. The hybridization analyses performed to study c-myc involvement in genital oncogenesis did not reveal c-myc amplification in either invasive or pre-invasive lesions.     

Detection of human papillomavirus DNA sequences in tongue squamous-cell carcinoma utilizing the polymerase chain reaction method.

Twenty-four cases of tongue squamous-cell carcinoma (SCC) were analyzed for human papillomavirus (HPV) DNAs by the polymerase chain reaction (PCR) method and the dot-blot hybridization technique. HPV DNAs were detected in 8 cases. One specimen histopathologically diagnosed as poorly differentiated grade-III SCC contained both HPV-16 and HPV-18 DNA, and 7 other cases contained HPV-16 DNA.     

Correlation of cervical carcinoma and precancerous lesions with human papillomavirus (HPV) genotypes detected with the HPV DNA chip microarray method

BACKGROUND: Human papillomavirus (HPV) infection is considered to play an important role in the development of cervical carcinoma, and it is known that certain HPV types, such as HPV-16 and HPV-18, are highly associated with cervical carcinoma. However, the pathologic behavior of other HPV types remains unclear. Recently, a new HPV detection technique, the HPV DNA chip, was introduced. The HPV DNA chip harbors 22 HPV probes and has the advantage of being able to detect 22 HPV types simultaneously. To evaluate the quality of the HPV DNA chip method and to identify HPV types related to cervical carcinoma and precancerous lesions, the authors performed HPV typing in cervical specimens from 1983 patients and compared their cytologic and histologic diagnoses. METHODS: The HPV DNA chip was used for HPV typing. Among 1983 patients who were tested for HPV types, cervical smear cytology was performed in 1650 patients, and 677 of those patients underwent cervical biopsy. RESULTS: Among the 1650 smears that were examined cytologically, 92.7% (114 of 123 smears) of low-grade squamous intraepithelial lesions (LSILs), 98.1% (106 of 108 smears) of high-grade squamous intraepithelial lesions (HSILs), and 96.3% (51 of 53 smears) of carcinomas were HPV positive, compared with only 35.1% of smears with normal cytology that were HPV positive. HPV-16 was the most prevalent type (chi-square test; P < 0.01) in LSILs (28.5%), in HSILs (51.9%), and in carcinomas (62.5%) followed by HPV-58 and a group of low-risk types (HPV-6, HPV-11, HPV-34, HPV-40, HPV-42, HPV-43,and HPV-44) in LSILs. HPV-58 (15.7%), HPV-18 (6.7%), and HPV-52 (4.6%) were the next most prevalent types after HPV-16 in HSILs. HPV-18 (11.4%) and HPV-58 (11.4%) were the second most common types in carcinomas. HPV-58 had the highest positive predictive value (54.9%) for the detection of histologically confirmed HSIL or carcinoma, whereas HPV 16 had the highest negative predictive value (80.6%). The sensitivity (96.0%) of the HPV test using the DNA chip method for detecting HSIL or carcinoma was superior compared with the sensitivity of cytologic diagnosis (83.6%). CONCLUSIONS: The HPV DNA chip provides a very sensitive method for detecting 22 HPV genotypes with reasonable sensitivity (96.0%) and reasonable negative predictive value (96.9%), and it overcomes the low sensitivity of cytologic screening for the detection of HSIL or carcinoma. HPV-58, HPV-52, and HPV-56, as well as HPV-16 and HPV-18, were associated highly with HSIL and carcinoma in the current large series. In addition, multiple HPV infection was associated less frequently with cervical carcinoma and with precancerous lesions compared with normal cytology.     

Human papillomavirus-31-related types predict better survival in cervical carcinoma

BACKGROUND: The aim of the current study was to explore the clinical implications and prognostic value of human papillomavirus (HPV) genotype in cervical carcinomas. METHODS: A total of 152 patients diagnosed with International Federation of Gynecology and Obstetrics Stage I-IV cervical carcinoma were studied between 1992-1999. HPV DNA status was assessed from paraffin-embedded, formaldehyde-fixed cervical carcinoma specimens by polymerase chain reaction-based methods using E7 type-specific and L1 modified general primers (MY11/GP6+ and GP5+/GP6+). The authors divided the patients into four groups: HPV-16-related, HPV-18-related, HPV-31-related, and HPV-58-related types. The relations with clinicopathologic data and overall survival were evaluated. RESULTS: HPV DNA was detected in 98% of the tumor specimens and 28.9% of the tumor specimens contained multiple HPV types. The HPV-16-related types were detected more often in squamous cell carcinomas, whereas the HPV-18-related types were more prevalent in adenocarcinomas and adenosquamous carcinomas. In addition, Stage I-II diseases were found more frequently in the HPV-16-related group than in the other groups (P = 0.001). Otherwise, no significant correlation between the HPV genotype and other clinicopathologic parameters was found. After a median follow-up of 64.5 months, the 5-year survival rate was 92% in the HPV-31-related group compared with 70% in the HPV-16-related group, 69% in the HPV-18-related group, and 36% in the HPV-58-related group. The survival rates statistically differed among the four groups by log-rank test (P = 0.02). However, the presence of multiple HPV types was not associated with prognosis. After stratifying for clinical stage, multivariate analysis demonstrated that HPV genotype was an independent prognostic factor. Compared with the HPV-16-related group, the long-term mortality rate was 73 % lower in the HPV-31-related group (relative risk, 0.27; 95% confidence interval, 0.09-0.76; P = 0.013). CONCLUSIONS: The presence of HPV-31-related types was an independent predictor of better survival in patients with cervical carcinoma. Therefore, HPV genotyping of cervical carcinomas may have profound implications for future patient management.     

Squamous cell carcinoma of the oral cavity rarely harbours oncogenic human papillomavirus

Although it is now well established that a significant proportion of oropharyngeal squamous cell carcinomas (SCC) harbour oncogenic human papillomavirus (HPV) sequences, the frequency with which these sequences are detected in oral SCC (excluding oropharyngeal subsites) is highly variable. In an attempt to establish the true prevalence of HPV-16 and HPV-18 subtypes in oral SCC, we screened 142 consecutive cases from a UK cohort using both conventional PCR with consensus primers and type-specific quantitative PCR (Q-PCR), while at the same time employing a rigorous protocol to avoid sample contamination. Q-PCR revealed HPV sequences in five cases; two contained HPV-16 alone, two HPV-18 alone, and one sample carried both genotypes. However, only two of these cases (both HPV-16-positive) had moderate viral loads (51 and 91 viral copies per 100 cells respectively) and were positive for HPV DNA by conventional PCR. Both cases contained HPV DNA in tumour cells as shown by Q-PCR analysis of micro-dissected tissue and by in situ hybridisation. The remaining three cases had only very low viral loads (between 3 and 7 viral copies per 100 cells), were negative by conventional PCR and lacked HPV DNA in tumour cells. Our data provide strong evidence that oncogenic HPV is uncommon in oral SCC and that routine HPV testing of these tumours cannot be advocated.     

Human papillomavirus-16 is integrated in lung carcinomas: a study in Chile

The human papillomavirus (HPV) was detected in 20 (29%) out of 69 lung carcinomas (LCs) in Chile, by PCR and Southern blot, and was more frequently detected in squamous cell carcinoma (SQC) than in adenocarcinomas (46 vs 9%, P=0.001). HPV-16, positive in 11 cases, was the most frequently detected HPV genotype determined by DNA sequencing. HPV-16 E2/E6 ratio, estimated from real-time PCR analysis, was much lower than the unity, suggesting that at least a partial HPV-16 genome was integrated in all but one HPV-16-positive SQCs. The remaining one case was suspected to have only episomal HPV-16. Although the viral load was low in most of the LCs, a case showed the HPV-16 copy number as high as 8479 per nanogram DNA, which was even a few times higher than the minimum viral load of seven cervical carcinomas (observed viral load: 3356-609 392 per nanogram DNA). The expression of the HPV-16/18 E6 protein was found in only two HPV-16-positive SQCs (13%) but not in the case with the highest viral load. Although the viral load was in general very low and HPV E6 expression is none or weak, further studies seem warranted to examine aetiological involvement of high-risk HPV in lung carcinogenesis.     

Decreased p21 Expression in HPV-18 Positive Cervical Carcinomas

The aim of this study was to investigate the relationship between different human papillomaviruse (HPV) genotypes and the expression of p53, p21 and p27 in cervical carcinomas. A total of 103 cases of cervical carcinomas were assayed for expression of p53, p21 and p27 by immunohistochemistry. HPV typing was carried out by two polymerase chain reaction-based methods. Overall, HPV prevalence was 97.1% among the cervical carcinomas in this study. HPV-16 was detected in 66% of the tumors, HPV-18 in 7.8%, HPV-16/18 in 7.8% and other HPV types in 15.5%. The expression of p53 and p27 was not related to HPV genotype. However, in the HPV-18 positive cervical carcinomas, expression of p21 was significantly decreased or completely absent (P = 0.019). Our results indicated that down-regulation of p21 was strongly associated with HPV-18 positive cervical carcinomas. The significantly lower expression of p21 protein in HPV-18 positive samples compared to HPV-18 negative cervical carcinomas supports the hypothesis that inactivation and degradation of p21 proteins by HPV-18 E7 may play an important role in the carcinogenesis of HPV-18 positive cervical neoplasia.     

Real-time quantitative PCR demonstrates low prevalence of human papillomavirus type 16 in premalignant and malignant lesions of the oral cavity.

PURPOSE: Human papillomavirus (HPV) type-16 has been associated with invasive squamous cell carcinoma of the head and neck. This study examines the role of HPV-16 in the progression of oral head and neck cancer by determining the quantity of HPV-16 DNA in premalignant and malignant lesions, using real-time quantitative PCR, to more accurately determine the role of HPV-16 in oral head and neck squamous cell carcinogenesis. EXPERIMENTAL DESIGN: We examined 102 microdissected premalignant head and neck lesions (85 from the oral cavity), 34 invasive oral cavity squamous cell carcinomas, as well as 18 invasive tumors known to be HPV positive by traditional molecular technology for the presence of HPV-16 DNA using real-time quantitative PCR. RESULTS: HPV DNA was detected in 1 of 102 premalignant lesions (0.98%), 1 of 34 (2.9%) invasive oral cavity carcinomas, and 14 of 18 (78%) known HPV-positive tumors. CONCLUSIONS: HPV-16 infection and integration is seldom found in oral premalignant lesions and invasive carcinoma, and therefore rarely contributes to malignant progression in the oral cavity. Furthermore, quantitative PCR is a useful technique that reliably excludes contaminated samples and those with minimal HPV DNA content that is unlikely to be significant in carcinogenesis.     

Human papillomavirus-16 and -18 in penile carcinomas: DNA methylation, chromosomal recombination and genomic variation

Penile carcinomas are frequently associated with high risk human papillomavirus (HPV) types. Because little is known about the molecular biology of this association, we investigated three properties of HPV genomes in penile carcinomas from Brazilian patients: (i) HPV DNA methylation, (ii) junctions between HPV and cellular DNA and (iii) genomic variation. In cervical carcinogenesis, recombination between HPV and chromosomal DNA is frequent and likely necessary for progression, and DNA hypermethylation-specifically of the L1 gene-is a biomarker for cancerous progression. The same mechanisms apparently occur during penile carcinogenesis, because 95 HPV-16 molecules derived from 19 penile lesions had 58% of the CpGs in L1 and 22% in the 5' part of the long control region methylated, more than the percentages found in cervical carcinomas. In addition, 2 out of 3 HPV-18 infections, all present in double infections with HPV-16, showed L1 specific methylation typical of malignant cervical lesions. In 11 out of 15 HPV-16 lesions, we confirmed chromosomal integration by reverse ligation inverted PCR, while 4 samples had concatemeric integrations or episomes. Nine of 17 penile carcinomas contained HPV-16 AA variants, and 8 E variants. As AA variants are relatively rare in Brazilian cohorts of asymptomatic women, the high prevalence in penile carcinomas may indicate a higher risk of progression of AA lesions, as suspected for cervical infections. Our observations of frequent viral DNA methylation, chromosomal integration and the prevalence of high risk variants suggest that HPV-dependent carcinogenesis of the penis and cervix follows similar etiological and epidemiological parameters.     

Prevalence of human papillomavirus in cervical cancer: a multicenter study in China

A large-scale epidemiologic survey on the prevalence of different types of human papillomavirus (HPV) in cervical cancer in China is indicated because of the implications for the development of diagnostic probes and vaccines against cervical cancer. A total of 809 cervical cancer specimens were collected from 5 regions in China including Shanghai, Guangzhou, Sichuan, Beijing and Hong Kong. HPV DNA was detected in 83.7% of the specimens. HPV-16 was present in 79.6%, HPV-18 in 7.5%, HPV-52 in 2.6% and HPV-58 in 3.8% of all HPV-positive specimens. The prevalences of HPV-16 and HPV-18 in Hong Kong were 61.7 and 14.8%, respectively, representing a lower HPV-16 and a higher HPV-18 proportion compared with the other regions. HPV-16 remained the most common HPV infection in both squamous cell carcinoma (SCC) and adenocarcinoma (AC). The proportion of HPV-18 infection was significantly higher in AC than in SCC.     

Prevalence and Distribution of High- and Low- Risk HPV Genotypes in Women Living in the Metropolitan Area of Naples: A Recent Update

Introduction: Human papillomavirus (HPV) can infect both male and female genitals, skin, and mucous membranes, causing benign or malignant lesions. HPV is a common sexually transmitted infection and it is the main cause of cervical cancer. The present retrospective study updated the previously published data on HPV genotypes distribution among women living in Naples. Materials and methods: In this study, 502 cervical scrape specimens were collected from women with abnormal cytological indication and analyzed for HPV DNA identification by Linear Array HPV genotyping test. Results: The HPV infection rate was 24.1%. HPV-16 (14.6%) was the most representative HR-HPV genotypes, followed by HPV-31 (13.8%), -18 (9.2%), and HPV-51 (8.5%). In addition, HPV-42 (16.4%) was the most prevalent genotype among LR-HPV  genotypes (low-risk human papillomavirus). It was also found that women at the age group of 23-29 years (42.5%) were at the highest risk of HPV infection. It was found that the HPV-16 frequency decreased, but HPV-31 and -18 frequency increased a little. The LR HPV-53 frequency decreased, leaving the first place for abundance to the LR HPV-42. HPV-6 frequency did not change. LR HPV -11 was no more present. Merging <23 and 23-29 age classes into one class followed the same result. Conclusion: HPV prevalence declined in comparison to the previous data. A frequency variation was recorded for several genotypes in this study.  Data can be useful to implement the preventative strategies and to promote HPV vaccination.     

Investigation of colon cancers for human papillomavirus genomic sequences by polymerase chain reaction.

Two previous studies have reported the presence of human papillomavirus (HPV) genomic sequences in colorectal cancers. We examined DNAs from 50 colorectal tumors for HPV sequences by polymerase chain reaction (PCR), using HPV consensus L1 primers for amplification. The PCR products were screened with a generic HPV probe consisting of amplimers of HPV-16 and HPV-18. All tumor DNAs were negative for HPV sequences. These results call into the question the reported association of colorectal cancers with HPVs.     

Human papillomavirus genotype distribution and cervical squamous intraepithelial lesions among high-risk women with and without HIV-1 infection in Burkina Faso

Human papillomavirus (HPV) infection and cervical squamous intraepithelial lesions (SILs) were studied in 379 high-risk women. Human papillomavirus DNA was detected in 238 of 360 (66.1%) of the beta-globin-positive cervical samples, and 467 HPV isolates belonging to 35 types were identified. Multiple (2-7 types) HPV infections were observed in 52.9% of HPV-infected women. The most prevalent HPV types were HPV-52 (14.7%), HPV-35 (9.4%), HPV-58 (9.4%), HPV-51 (8.6%), HPV-16 (7.8%), HPV-31 (7.5%), HPV-53 (6.7%), and HPV-18 (6.4%). Human immunodeficiency virus type 1 (HIV-1) seroprevalence was 36.0%. Human papillomavirus prevalence was significantly higher in HIV-1-infected women (87 vs 54%, prevalence ratio (PR) = 1.61, 95% confidence interval (CI): 1.4-1.8). High-risk HPV types (71 vs 40%, PR = 1.79, 95% CI: 1.5-2.2), in particular HPV-16+18 (22 vs 9%, PR = 2.35, 95% CI: 1.4-4.0), and multiple HPV infections (56 vs 23%, PR = 2.45, 95% CI: 1.8-3.3) were more prevalent in HIV-1-infected women. High-grade SIL (HSIL) was identified in 3.8% of the women. Human immunodeficiency virus type 1 infection was strongly associated with presence of HSIL (adjusted odds ratio = 17.0; 95% CI 2.2-134.1, P = 0.007) after controlling for high-risk HPV infection and other risk factors for HSIL. Nine of 14 (63%) HSIL cases were associated with HPV-16 or HPV-18 infection, and might have been prevented by an effective HPV-16/18 vaccine.     

Papillomavirus and cancer

Papillomaviruses are causative agents of benign tumor (papilloma) and are widely distributed in most of animals. The papillomaviruses are small DNA viruses grouped in the papovavirus family. The genomes of all papillomaviruses pce double stranded circular DNA of approximately 8 K. base pairs. Classification of the viruses is presently based on the host range and relatedness of the nucleic acids. In the case of human papillomavirus (HPV), more than 50 types have been isolated. The amount of information about the HPV has grown considerably in the last few years, and at present it has been considered that the specific types of HPV are involved in the development of human genital cancer and the skin cancer developed in the patients with EV (epidermodysplasia verruciformis). The reasons are; i) Epidemiological evidence distinctly indicates that cervical carcinoma and other high-grade lesions of female and male genital tracts derive from a sexually transmitted disease. ii) Many cervical carcinomas, most cell lines derived from the carcinoma and almost all skin tumors of EV patient contain specific types of HPV DNA (genital tumors; HPV-16, 18, 31, 33 and 25, skin tumor of EV patient; HPV-5, 8, 17 and 20). Moreover, genetic information of the viruses can be detected in the cancer cells. iii) Follow-up studies of HPV carriers suggested that HPV-16, 18 have high oncogenic potential. iv) Oncogenic functions (transformation and immortalization) can be detected in the early genetic region of HPV-16 DNA. v) Cottontail rabbit papillomavirus (CRPV) induces tumor in rabbit (and that almost all of these tumors contain CRPV DNA. When rabbits are infected with CRPV, benign papillomas are induced in 100% of the rabbits and the lesion are progressed to skin cancer at the frequency of 40-60%). In human cases, however, the presence of specific types of HPV does not seem to be sufficient to assure the development of benign tumors into carcinomas, since only a part of all such cases progress after latent period of several to several ten years. This emphasizes that other etiological agents or cofactors must be involved.     

Occurrence of vaccine and non-vaccine human papillomavirus types in adolescent Finnish females 4 years post-vaccination

Control of human papillomavirus (HPV)-related cancers by inclusion of HPV vaccination into national vaccination programmes is likely. One open question is replacement of the vaccine types with other high-risk (hr) HPV types in the vaccination era. We studied occurrence of HPV types in adolescent females participating in a population-based vaccination trial. A total of 4,808 16- to 17-year-old females from Finland were enrolled in the 1:1 randomized phase III (PATRICIA) trial of the efficacy of vaccination with the AS04-adjuvanted HPV-16/18 virus-like particle vaccine as compared to hepatitis A virus (HAV) vaccine. HPV infection was assessed from cervical samples taken every 6 months for 4 years post-vaccination by polymerase chain reaction (PCR) for genital oncogenic HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 58, 59, 66, 68, and 73 as well as low-risk types HPV-6 and HPV-11. The HPV-16/18 vaccine coverage ranged between 1 and 22% by age-cohort and study community. Odds ratios (ORs) for infections with different HPV types in baseline PCR negative HPV-16/18 vs. HAV vaccinated women, and Poisson regression derived HPV incidence rate ratios (IRRs) in baseline positive vs. negative women were calculated. The OR and IRR estimates for acquisition of any genital HPV types showed no excess risk neither in baseline HPV DNA-negative HPV-16/18-vaccinated women compared to baseline HPV DNA-negative HAV vaccinated women nor in HPV-16/18-vaccinated baseline HPV-16/18-positive women compared to baseline HPV-16/18-negative women. In the HAV-vaccinated, baseline HPV-18-positive women showed an increased risk of acquiring other clade A7 HPV types (39, 45, 59, 68) (IRR 1.8, 95% confidence interval = 1.01.-3.1). We found no increased occurrence of non-vaccine HPV types suggestive of type-replacement 1–4 years post-vaccination among HPV-16/18-vaccinated Finnish adolescents.