Single and multiple human papillomavirus infections in cervical abnormalities in Portuguese women

Persistent infection with high-risk (HR) human papillomavirus (HPV) types is necessary for cervical cancer development. However, little is known about the influence of multiple HPV infections on cervical lesion risk. The aim of this study was to evaluate the frequency of single and multiple HPV infections in Portuguese women, and to assess the frequency of multiple infections in cervical intraepithelial neoplasia (CIN). HPV prevalence, type-specific prevalence and extent of multiple infections were assessed in 1057 cervical samples. The Clinical Array HPV assay was used to detect 35 HPV types. According to histological diagnosis, 425 samples were normal, 375 were CIN1, and 257 were CIN2+. HPV status was studied in relation to age and lesion severity. The prevalence of HPV infection was 52.7%; 25.4%, 67.2% and 76.7% were positive for any HPV type in the normal, CIN1 and CIN2+ cases, respectively. Among HPV-positive cases, 32.0% were associated with multiple infections. Among multiple infections, 96.1% harboured HR HPV types and 38.2% HR–low risk (LR) HPV types. Overall, 33 different HPV types (18 HR and 15 LR) were detected. HR HPV types (44.1%) were significantly more prevalent than LR HPV types (8.6%). The most frequent genotype was HPV 16 (25.5%), followed by HPV 31, 53, 66, 58, and 51. Multiple infections showed a significant increase (p 0.005) according to severity of neoplasia, particularly for HR–HR HPV infections (p 0.003). No association between age and multiple HPV infections was observed (p 0.812). However, multiple HR HPV infections were more frequent in women under 30 years of age (35.3%).     

Multiple human papilloma virus types in cervical infections: competition or synergy?

Mejlhede N, Pedersen BV, Frisch M, Fomsgaard A. Multiple human papilloma virus types in cervical infections: competition or synergy? APMIS 2010; 118: 346–52. Coinfection with multiple human papilloma virus (HPV) types is common in cervical HPV infection. To evaluate if infections with different HPV types occur independently, we examined 3558 women above 15 years of age suspected of cervical HPV infection. Among them, 1842 (52%) women were HPV negative and 1716 (48%) were HPV positive as analysed by a PCR‐based commercial microarray assay for mucosal types. Of the HPV‐positive samples, 824 (48%) had single infections, while 892 (52%) had multiple infections. Observed numbers of concurrent HPV types differed from expected numbers under the assumption of independence between infections by the various HPV types. Significant positive associations were observed for 16 pairs of HPV types in statistical analysis accounting for mass significance. Significant negative associations were also found, i.e. women with HPV‐16 infection had 0.4 times the odds of having HPV‐51 compared with women not infected with HPV‐16. HPV‐16 was the only type with odds ratios <1 for all pairwise combinations. While our findings of statistically significant coexistence do not prove biological dependence among HPV types, they do suggest that infections with some HPV types may depend on the existence of certain other HPV types. Any interaction between coexisting HPV types could either decrease or increase the efficacy of current HPV vaccines that offer mainly type‐specific protection, depending on whether the types vaccinated against compete with other HPV types or not.     

Distribution of human papillomavirus genotypes in cervical intraepithelial neoplasia and invasive cervical cancer in Canada

Infection with high‐risk human papillomavirus (HPV) causes cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC). The distribution of HPV types in cervical diseases has been previously described in small studies for Canadian women. The prevalence of 36 HPV genotypes in 873 women with CIN and 252 women with ICC was assessed on cervical exfoliated cells analyzed with the Linear Array (Roche Molecular System). HPV16 was the most common genotype in CIN and ICC. The seven most frequent genotypes in order of decreasing frequency were HPV16, 51, 52, 31, 39, 18, and 56 in women with CIN1, HPV16, 52, 31, 18, 51, 39, and 33 in women with CIN2, HPV16, 31, 18, 52, 39, 33, and 58 in women with CIN3, and HPV16, 18, 45, 33, 31, 39, and 53 in women with ICC. HPV18 was detected more frequently in adenocarcinoma than squamous cell carcinoma (P = 0.013). Adjustment for multiple type infections resulted in a lower percentage attribution in CIN of HPV types other than 16 or 18. The proportion of samples containing at least one oncogenic type was greater in CIN2 (98.4%) or CIN3 (100%) than in CIN1 (80.1%; P < 0.001 for each comparison). Multiple type infections were demonstrated in 51 (20.2%) of 252 ICC in contrast to 146 (61.3%) of 238 women with CIN3 (P < 0.001). Adjusting for multiple HPV types, HPV16 accounted for 52.1% and HPV18 for 18.1% of ICCs, for a total of 70.2%. Current HPV vaccines should protect against HPV types responsible for 70% of ICCs in Canadian women. J. Med. Virol. 83:1034–1041, 2011. © 2011 Wiley‐Liss, Inc.     

Cervical and oral human papillomavirus types in HIV-1 positive and negative women with cervical disease in South Africa

This study tested cervical and oral human papillomavirus (HPV) infection in HIV-1 seropositive (HIV+) and seronegative (HIV-) women to determine any association between infections at both sites and the difference in prevalence of the HPV types infecting these women. Participants were 115 women referred to a colposcopy clinic after diagnosis of abnormal cervical cytology. The women showed low grade cervical intraepithelial neoplasia (CIN1) or high grade disease (CIN2/3) or no CIN based on colposcopy and histology. Typing of HPV in cervical and oral cells was by Roche linear array and included direct sequencing on selected oral samples. Cervical HPV prevalence was 86.5% and 97.1% in HIV- and HIV+ women respectively. With the exception of HPV-45, prominent in HIV+ women, the hierarchy of predominant types were similar in HIV- and HIV+ women. HPV-16 was most prevalent in both HIV+ (41.7%) and HIV- women (38.5%) with CIN2/3. Significantly more HIV+ women had multiple cervical (>1) infections than HIV- women (36.1% vs. 88.2%, P < 0.001) and more oral HPV infections (45.5% and 25% respectively; P = 0.04). The most prevalent oral HPV types were HPV-33, -11, and -72. The majority of women did not have concordant oral and cervical HPV types, reflecting possible independence of infection at the two sites. HIV immune suppression did not impact significantly on the predominant types of cervical HPV infection (except for HPV-45). HIV+ women had more multiple HPV infections and those with severe cervical disease a similar prevalence of HIV-16 but a lower HPV-18 prevalence than HIV- women.     

Prevalence of HPV 16 and 18 DNA sequences in CIN III lesions of adults and adolescents

Adolescents may be more susceptible to cervical human papillomavirus (HPV) infections and may have more rapid progression of cervical intraepithelial neoplastic (CIN) lesions than adults. We evaluated Papanicolaou (Pap) smears and cervical tissue specimens from a consecutive series of 25 adolescent (age 15-20 yr) and 17 adult (age 35-40 yr) patients with a histologic diagnosis of CIN III. The study patients were all Detroit residents enrolled in a health maintenance organization (HMO) affliated with Henry Ford Hospital. The cervical tissue specimens were evaluated for HPV 6b/11, HPV 16, and HPV 18 using agarose gel electrophoresis and Southern hybridization following polymerase chain reaction (PCR) DNA amplification. While the small sample size precluded testing for statistical significance, HPV 16 and/or HPV 18 DNA was detected in specimens from 21/25 (84%) adolescents compared to 12/17 (71%) adults (odds ratio [OR] = 2.2; 95% confidence interval [CI] = 0.49-9.74). The relationship between adolescence and HPV infections appears to be stronger for HPV 18 and mixed HPV 16/18 infections (OR = 5.6; 95% CI = 0.7-42.4) than for HPV 16 infections (OR = 1.93; 95% CI = 0.4-8.8). None of the cervical specimens contained HPV 6b/11 DNA. Oral contraceptive (OC) use was associated with HPV infection in patients with CIN III, but there was no association between cigarette smoking and HPV infection. The effect of OC use on the relationship of age and HPV could not be evaluated due to small sample size. The effects of previous sexually transmitted disease (STD) on the relationship of age and HPV were assessed. Among women with a history of STD, there was a strong association between HPV and adolescent age (OR = 18.0; 95% CI = 1.2-260.0). Our data suggest that among women with CIN III, adolescents have a higher prevalence of certain high-risk types of HPV infections than adults. The excess is due predominantly to the higher rates of HPV 18 and mixed HPV 16/18 infections in adolescents. The positive relationship between high-risk HPV infections and young age was most evident in adolescents with a history of STD. The results from this study suggest that differences in HPV type infections may be related to the more aggressive clinical course of CIN in adolescents. © 1994 Wiley-Liss, Inc.     

Cervical infections by multiple human papillomavirus (HPV) genotypes: Prevalence and impact on the risk of precancerous epithelial lesions

A large proportion of human papillomavirus (HPV) infections is sustained by multiple genotypes. The effect of multiple infections on the risk of cervical intraepithelial neoplasia (CIN) and the potential efficacy of vaccine on these infections are controversial. We performed viral typing by SFP₁₀‐LIPA on a consecutive series of 1,323 women undergoing colposcopy, 69% of whom had cervical biopsy, and correlated CIN severity with the type and number of HPVs. Overall prevalence of HPV‐DNA was 68.9%, 97.3% in CIN1, and 98.1% in CIN≥2. HPV positivity correlated with younger age (35.9 vs. 37.3 years, P = 0.026) and history of CIN (P < 0.001). Multiple types were detected in 44.2% of cases, including 63.1% CIN1 and 80.8% CIN≥2. Twenty‐three different types were detected, HPV‐16, 31 and 52 being the most frequent. Infections by HPV‐6, 11, 16, or 18 occurred in 59.4% of CIN1 and 71.3% of CIN≥2. Number of viral types and class of oncogenic risk were linearly correlated with CIN severity (P < 0.0001) by univariate and multivariate analyses controlling for age and history of CIN. The effect of the number of HPV types was maintained after exclusion from the model of infections by HPV‐6, 11, 16, and 18. Frequency, distribution, and clinical correlates of multiple HPV infections highlight the importance of assessing individual types in the management and the prediction of outcome of women with abnormal baseline cytology and point to potential limitations in current vaccine strategies. J. Med. Virol. 81:703–712, 2009 © 2009 Wiley‐Liss, Inc.     

Infection with high‐risk HPV types among female sex workers in northern Vietnam

Vaccines against two high‐risk human papillomavirus (HPV) types, HPV‐16, and HPV‐18, are in use currently, with high efficacy for preventing infections with these HPV types and consequent cervical cancers. However, circulating HPV types can vary with geography and ethnicity. The aim of this study was to investigate the prevalence of HPV types and the association between HPV types and abnormal cervical cytology among female sex workers in Northern Vietnam. Cervical swabs and plasma samples were collected from 281 female sex workers at two health centers in Hanoi and Hai Phong in 2009. The HPV L1 gene was amplified by PCR using original and modified GP5⁺/6⁺ primers. Amplified PCR products were genotyped by the microarray system GeneSquare (KURABO) and/or clonal sequencing. Of the 281 women, 139 (49.5%) were positive for HPV DNA. Among the HPV‐positive samples, 339 strains and 29 different types were identified. Multiple‐type and high risk‐type HPV infections were found in 85 (61.2%) and 124 (89.2%) women, respectively. The most common genotype was HPV‐52, followed by HPV‐16, HPV‐18, and HPV‐58. Abnormal cervical cytology was detected in 3.2% (9/281) of the women, and all of these samples were positive for HPV‐DNA. Age ≤25 years and infection with human immunodeficiency virus were associated positively with HPV infection among the women while ever smoking was associated negatively. These results show that HPV‐52 is most prevalent among female sex workers in Northern Vietnam, most of whom had normal cervical cytology. This information may be important for designing vaccination strategies in Vietnam. J. Med. Virol. 85:288–294, 2013. © 2012 Wiley Periodicals, Inc.     

The relationship between the cervical and anal HPV infection in women with cervical intraepithelial neoplasia

BackgroundMore than 90% of cases of anal cancers are caused by high-risk human papillomavirus (HR HPV) infection and a history of cervical intraepithelial neoplasia (CIN) is established as possible risk factor.ObjectivesTo demonstrate relationship between anal and cervical HPV infection in women with different grades of CIN and microinvasive cervical cancer.Study designA total of 272 women were enrolled in the study. The study group included 172 women who underwent conization for high-grade CIN or microinvasive cervical cancer. The control group consisted of 100 women with non-neoplastic gynecologic diseases or biopsy-confirmed CIN 1. All participants completed a questionnaire detailing their medical history and sexual risk factors and were subjected to anal and cervical HPV genotyping using Cobas and Lynear array HPV test.ResultsCervical, anal, and concurrent cervical and anal HPV infections were detected in 82.6%, 48.3% and 42.4% of women in the study group, and in 28.0%, 26.0% and 8.0% of women in the control group, respectively. The prevalence of the HR HPV genotypes was higher in the study group and significantly increased with the severity of cervical lesion. Concurrent infections of the cervix and anus occurred 5.3-fold more often in the study group than in the control group. Any contact with the anus was the only significant risk factor for development of concurrent HPV infection.ConclusionsConcurrent anal and cervical HR HPV infection was found in nearly half of women with CIN 2+. The dominant genotype found in both anatomical locations was HPV 16. Any frequency and any type of contact with the anus were shown as the most important risk factor for concurrent HPV infection.     

One virus, one lesion--individual components of CIN lesions contain a specific HPV type

In 20-40% of cervical intra-epithelial neoplasia (CIN) and in 4-8% of cervical carcinoma tissue specimens, multiple HPV genotypes have been detected. Whole tissue section (WTS) PCR does not determine how the individual types relate causally to complex and multiple CIN. Our objective was to determine whether laser capture micro-dissection (LCM) with HPV PCR genotyping (LCM-PCR) could accurately recover type-specific HPV DNA from epithelial cells in individual areas of CIN and normal epithelium, and whether one or more viruses are present in one lesion. For that, histologically selected samples of CIN and normal epithelium were isolated by LCM and analysed by the SPF(10) PCR/LiPA(25) (version 1) HPV genotyping system for 25 HPV genotypes. HPV genotypes detected in 756 areas of CIN (grade 1, 2 or 3) by LCM-PCR were compared with results obtained by WTS-PCR in 60 cases (74 biopsies). We showed that when a single HPV type is detected by WTS-PCR, that type was almost always (94%; 29/31) recovered by LCM-PCR from CIN. When multiple HPV types were present by WTS-PCR, their distribution within histological sections could be mapped by LCM-PCR. Association of a single HPV type with a discrete area of CIN was found for 93% (372/399) of LCM fragments analysed by PCR. We found colliding CIN lesions associated with separate HPV types and only 62% (61/99) of HPV types detected by WTS-PCR were found in CIN by LCM-PCR. Therefore, the LCM-PCR technique was found very accurate for high-resolution HPV genotyping and for assigning an individual HPV type to an area of CIN. At LCM level, in cervical biopsy sections with multiple HPV infections, the relation between HPV types and CIN lesions is often complex. Almost every HPV type found in CIN by LCM-PCR is associated with a biological separate independent CIN lesion-one virus, one lesion.     

Comparison of the performance in detection of HPV infections between the high‐risk HPV genotyping real time PCR and the PCR‐reverse dot blot assays

A new multiplex real‐time PCR assay, the high‐risk HPV genotyping real time PCR assay (HR HPV RT‐PCR), has been developed to detect 15 high‐risk HPV types with respective viral loads. In this report, a total of 684 cervical specimens from women diagnosed with vaginitis were assessed by the HR HPV RT‐PCR and the PCR reaction and reverse dot blot (PCR‐RDB) assays, using a PCR‐sequencing method as a reference standard. A total coincidence of 97.7% between the HR HPV RT PCR and the PCR‐RDB assays was determined with a Kappa value of 0.953. The HR HPV RT PCR assay had sensitivity, specificity, and concordance rates (accuracy) of 99.7%, 99.7%, and 99.7%, respectively, as confirmed by PCR‐sequencing, while the PCR‐RDB assay had respective rates of 98.8%, 97.1%, and 98.0%. The overall rate of HPV infection, determined by PCR‐sequencing, in women diagnosed with vaginitis was 49.85%, including 36.26% of single infection and 13.6% of multiple infections. The most common infections among the 15 high‐risk HPV types in women diagnosed with vaginitis were HPV‐52, HPV‐16, and HPV‐58, with a total detection rate of 10.23%, 7.75%, and 5.85%, respectively. We conclude that the HR HPV RT PCR assay exhibits better clinical performance than the PCR‐RDB assay, and is an ideal alternative method for HPV genotyping. In addition, the HR HPV RT PCR assay provides HPV DNA viral loads, and could serve as a quantitative marker in the diagnosis and treatment of single and multiple HPV infections.     

Detection of HPV in Norwegian cervical biopsy specimens with type-specific PCR and reverse line blot assays.

BACKGROUND: Although the association of HPV16 and HPV18 DNA with cervical cancers has been well studied, the prevalence of these types in high-grade cervical intraepithelial neoplasias (CIN2/3) may differ from the prevalence found in cervical cancer specimens. OBJECTIVE: To determine the prevalence of specific HPV types found in high-grade CIN2/3 biopsy samples. STUDY DESIGN: One thousand eight hundred and forty-eight cervical biopsy specimens were obtained from Norwegian women. HPV16 and HPV18 type and gene-specific PCR assays were performed amplifying a portion of the E6, E7 and L1 genes. In addition, the reverse line blot assay was performed on a subset of specimens, in which a portion of L1 was amplified and hybridized to strips coated with complimentary HPV sequences. RESULTS: The prevalences of HPV16 and HPV18 in the 1848 biopsy cohort were 32.3% and 6.0%, respectively. HPV16 was detected in 47.5% and HPV18 in 5.9% of diagnosed CIN2/3 specimens. Approximately 12% of the CIN2/3 specimens contained two HPV types and 2.5% contained three HPV types. CONCLUSIONS: The prevalence of HPV16 increases from grades CIN1 to CIN2 to CIN3. The prevalence of HPV18 did not change significantly with increasing CIN grade. The majority of infections diagnosed as CIN2/3 contained a single HPV type. The type-specific PCR assay had increased detection sensitivity over the reverse line blot assay.     

The prevalence of VAIN,CIN, and related HPV genotypes in Japanese women with abnormal cytology

Vaginal intraepithelial neoplasia (VAIN) is often found by chance. We investigated the prevalence of VAIN and related human papillomavirus (HPV) types in comparison with cervical intraepithelial neoplasia (CIN). This study enrolled 648 women who were referred to the outpatient clinic of Kanazawa Medical University Hospital for abnormal cytology from January 2009 to January 2019. HPV genotypes were determined using Genosearch-31 + 4, which can detect 35 different HPV types. Colposcopy was performed at the first visit by an experienced gynecological oncologist. Among 611 subjects with squamous cell lesions, 107 (17.5%) VAIN cases were identified, and 67 (11.0%) women had both VAIN and CIN. Ultimately, 72 VAIN1, 15 VAIN2/3, 203 CIN1, 249 CIN2/3, 32 cervical squamous cell carcinomas (SCC), and one vaginal SCC (Vag-SCC) were identified. The prevalences of VAIN1, VAIN2/3, and Vag-SCC were 35.5%, 6.0%, and 3.1% of equivalent cervical lesions, respectively. The VAIN patients were older than the CIN patients (P = .002). About half of the VAIN cases were diagnosed during the follow-up. Multiple HPV infections were found in 42.9% of the VAIN and CIN patients. HPV52, 16, 51, 53, and 56 were the most common types in VAIN, whereas HPV16, 52, 58, 51, and 31 predominated in CIN. HPV18 was rare in VAIN, HPV58 was more common in CIN than in VAIN, and HPV53 and HPV73 were more common in VAIN. In conclusion, VAIN1 was identified more frequently than we expected. Various HPV types were identified in the vagina, which is likely a reservoir for HPV.     

Typing of human papillomavirus in women with cervical lesions: Prevalence and distribution of different genotypes

Human papillomavirus (HPV) are distributed widely and persistent infection with high‐risk (HR) HPV is recognized as a necessary cause of cervical cancer. The aim of this study was to evaluate the distribution of different HR‐HPV genotypes in 199 women with cervical pre‐invasive lesions undergoing conservative treatment. A Linear Array HPV Genotyping Test was used to identify individual HPV genotypes in cervical samples. It was observed that the most prevalent HPV genotypes were HPV 16 (52.6%), HPV 51 (13.5%), and HPV 31 (10.9%); HPV 18 was found in 7.3% of the patients. Stratifying the different HPV genotypes according to the severity of the cervical lesion, a strong association between the increasing severity of the histological diagnosis and the detection of more carcinogenic HR‐HPV type was found, and in all but one cervical intraepithelial neoplasia of grade 3 the presence of at least one HR‐HPV could be detected, with more than 70% of cervical intraepithelial neoplasia of grade 3 patients bearing HPV 16. Multiple infections, comprising between 2 and 6 HPV types, were found in 43% of patients; however, the presence of more than 1 HR‐HPV type was not associated with an increased risk of high grade lesions. In conclusion, this data show that HPV 16, 51, 31, 52, and 18 were the prevalent types found in patients with cervical lesion undergoing conservative treatment, with a high prevalence of HPV 16 in cervical intraepithelial neoplasia of grade 3 patients. No association between multiple infection and severity of the lesion could be found. J. Med. Virol. 81:271–277, 2009. © 2008 Wiley‐Liss, Inc.     

UK population based study to predict impact of HPV vaccination

BackgroundIn 2008 a human papillomavirus (HPV) vaccination programme for cervical cancer prevention was implemented in the UK. Surveillance of vaccine uptake, impact on prevalence of HPV infection and cervical cancer incidence were identified as key measures to evaluate the intervention.ObjectiveTo determine baseline HPV prevalence in unvaccinated women and predict impact of HPV vaccination on high-grade cervical disease (CIN2+).Study designA pseudo-anonymous prospective cohort was sampled on entry to the routine cervical screening programme between March 2009 and November 2010. In total, 13,306 eligible females were identified and high-risk (hrHPV) type specific status determined. Potential impact of prophylactic vaccination on CIN2+ was calculated by applying HPV vaccine clinical trial data to the baseline HPV type-specific data.ResultsOf 13,306 samples tested, 3545 (26.6%) were confirmed positive for at least one hrHPV type and 1325 (10%) were positive for low risk HPV. HPV16 was the predominant type detected in cases positive with either single or multiple hrHPV infection(s) (5.2% and 4.7%, respectively). Based on hrHPV type-specific data, Gardasil would have prevented 33.2% HPV16/18 unrelated CIN2+ compared to 47.1% for Cervarix. This difference was not statistically significant.ConclusionPrior to the introduction of the HPV vaccine, approximately one-quarter of young women were positive for hrHPV and one-tenth positive for HPV16. Post-vaccination, we anticipate a substantial absolute risk reduction in high-grade cervical disease associated with both targeted and non-targeted hrHPV types. There is no significant difference between the two commercially available vaccines in terms of clinical impact.     

The relationship of community biopsy-diagnosed cervical intraepithelial neoplasia grade 2 to the quality control pathology-reviewed diagnoses: an ALTS report

We examined the predictors (cytologic interpretations, pathology review, human papillomavirus [HPV] testing results, and colposcopic impressions) of precancer among 545 women with clinical center biopsy diagnoses of cervical intraepithelial neoplasia (CIN) 2 in the ASCUS LSIL Triage Study. Among women with a CIN 2 biopsy result, there was an increasing likelihood that the loop electrosurgical excision procedure (LEEP) tissue sample was diagnosed as precancer (CIN 3) with an increasing number of clinical risk factors of cervical precancer (high-grade squamous intraepithelial lesion [HSIL] cytology, high-grade colposcopy, detection of HPV type 16; Ptrend < .0005). In a multivariate model, using a case definition of worst histologic diagnosis made by the quality control pathology review of biopsy and LEEP tissue samples, HPV-16 was positively associated (odds ratio [OR], 4.8; 95% confidence interval [CI], 2.6-8.8) with a CIN 3 diagnosis, whereas testing negative for HPV or positive for noncarcinogenic HPV types was negatively associated (OR, 0.32; 95% CI, 0.14-0.75) with a CIN 3 diagnosis. Although we found clear evidence that HPV-16 detection helped clarify whether a biopsy specimen diagnosed as CIN 2 represented HPV infection or cervical precancer, this relationship was not sufficiently robust to be clinically useful for reducing the overtreatment of women with HPV infection.     

In situ human papillomavirus (HPV) genotyping of cervical intraepithelial neoplasia in South African and British patients: evidence for putative HPV integration in vivo.

In South Africa asymptomatic wart virus infection diagnosed by morphological criteria occurs in 16-20% of all ethnic groups; the incidence in black women is 66%. To identify human papillomavirus (HPV) types the prevalence of HPV in cervical intraepithelial neoplasia (CIN) in South African women (n = 72) with age matched British women (n = 73) was compared by non-isotopic in situ hybridisation (NISH) using digoxigenin labelled probes for HPV 6, 11, 16, 18, 31, 33 and 35 on archival biopsy specimens. A higher proportion of British biopsy specimens (68%) contained HPV than those from South Africa (50%) in CIN 2 and 3; this difference was due to HPV 16. Thirty six per cent of the positive biopsy specimens from South African women also contained HPV 33/35 compared with 16% in the United Kingdom. There was no difference in HPV detection with age in either group. These data indicate that HPV types vary geographically, with "minor" HPV types being more common in South Africa. Three qualitatively distinct NISH signals were observed; a diffuse (type 1) signal in superficial cells, mainly koilocytes; a punctate signal (type 2) in basal/"undifferentiated" cells in CIN 3; and combined type 1 and 2 signals in CIN with wart virus infection (type 3). The punctate signal may represent HPV integration.     

Cervicovaginal, oral, and serum IgG and IgA responses to human papillomavirus type 16 in women with cervical intraepithelial neoplasia

Oncogenic human papillomaviruses (HPVs) are obligate mucosal pathogens and typically cause localized infections. The mucosal surface of the genital tract also provides the first line of defense against genital HPV infection. Although local antibody production following HPV-infection has been demonstrated, their role in protection from cervical disease is unclear. This study evaluated oral and cervical HPV infection and the associated linkage between HPV-16 oral, cervical and serum antibody responses in 103 women with varying grades of cervical intraepithelial neoplasia (CIN). We found that HPV-16 was the most prevalent cervical HPV infection (30/103, 29.1%) but was only detected in 1.1% (1/91) of the oral samples. Both the frequency and magnitude of HPV-16-specific cervical IgA was significantly elevated in women with CIN 2/3 compared with women with CIN 1 (P = 0.0073 frequency; P = 0.0045 magnitude). Women with cervical HPV-16 infection had significantly higher magnitude and frequency of cervical HPV-16 IgA responses than women without cervical HPV-16 DNA (P = 0.0002 frequency; P = 0.0052 magnitude). Despite our contention that mucosal HPV-16 antibody responses within distinct mucosal compartments may be linked, the concordance analysis carried out within and between mucosal compartments and serum suggests that no such linkage exists and that these compartments may be functioning independently of one another. An HPV-16 specific antibody response in one mucosal compartment in women with CIN is therefore not predictive of a response at another.     

Prevalence of human papillomavirus types in cervical lesions from women in rural Western India

Cervical cancer is the most common cancer among women in many areas of India which contributes for a fifth of the global burden of disease. Persistent infection with one of the high-risk human papillomaviruses (HPV) has been established as the cause for cervical cancer and the documentation of the prevalence of HPV types in cervical cancer in different regions of India is useful for a prevention program combining both screening and vaccination. In this study, the HPV type distribution and the frequency of p16(INK4a) immunoexpression have been determined in 125 cases of inflammatory lesions or grade 1 cervical intraepithelial neoplasia, 74 cases of grade 2, 72 cases of grade 3, and 113 cervical cancer cases diagnosed among women from rural Solapur and Osmanabad districts, Maharashtra. The overall prevalence of high-risk HPV was 37.6% in inflammatory lesions or grade 1 cervical intraepithelial neoplasia, 63.5% in grade 2, 97.2% in grade 3 and 92% in cervical cancer cases. HPV 16 and HPV 18 were detected in 80.6% of grade 3 cervical intraepithelial neoplasia and 86.5% of cervical cancer cases. 94.7% of the cervical cancer and 84.4% of the high grade lesions with a strong and full thickness staining for p16(INK4a) were positive for HPV infection; p16(INK4a) immunoexpression increased with worsening grade of cervical intraepithelial neoplasia. The HPV genotyping data showing a high HPV 16 and 18 prevalence in cancer specimens indicate that prophylactic HPV 16/18 vaccination would have a significant impact on the prevention of cervical cancer in India.     

Genotypes and prevalence of HPV single and multiple concurrent infections in women with HSIL

The contribution of human papillomavirus (HPV) types to the carcinogenesis of cervical cancer has been established for a long time. However, the role of phylogenetically related and rare variants remains uncertain, as well as the influence of concurrent multiple HPV genotypes infection. We aimed at studying the prevalence of several HPV genotypes infecting women with single versus concurrent multiple HPV genotypes infection with a HSIL diagnosis in a cervical cytology. We conducted a cross‐sectional study using Thin‐Prep^® liquid‐based cervical cytology specimens with the diagnosis of high‐grade squamous intraepithelial lesion (HSIL), in which HPV genotype was sequentially tested. Genotypes were determined with a PapilloCheck^® system, a DNA‐Chip for the type‐specific identification of 18 high‐risk and six low‐risk types of HPV. Of the total study population, 176 cases had a diagnosis of HSIL and positive HPV genotyping result, being HPV16 the most prevalent genotype (48.86%; 95%CI: 41.58–56.19) followed by HPV31 (14.20%; 95%CI: 9.75–20.18). Concurrent multiple HPV genotypes were detected in 36.93% (95%CI: 30.15–44.27) of the patients. The prevalence of the 10 most common HPV genotypes detected varied significantly according to the presence of single vs. concurrent multiple HPV genotypes (P = 0.022). Moreover, women with concurrent multiple HPV genotypes were on average 3.53 (95%CI: 0.43–6.64) years younger than women with single genotype infection. Our results suggest that women with multiple genotype HPV infection differ in terms of age and distribution of the most prevalent HPV genotypes. Additionally, we provide further evidence of the predominance of HPV16 in HSIL lesions of the uterine cervix. Diagn. Cytopathol. 2014;42:919–923. © 2014 Wiley Periodicals, Inc.     

High prevalence of human papillomavirus infection in Eastern European and West African women immigrants in South Italy

Surveillance of human papillomavirus (HPV) prevalence and genotype distribution in migrant women from middle and low-income countries to developed countries is limited. The aim of this study was to analyze the spectrum of HPV genotypes and prevalence of cervical abnormalities in women emigrated mainly from Eastern Europe and West Africa and living in Southern Italy. The study included 233 migrant and 98 Italian-born women who self-referred to two gynecological outpatient clinics in the Campania region. Cervical specimens were subjected to cytological examination and viral testing by broad spectrum PCR. The prevalence rates of HPV infection were 57.9% and 94.1% among migrant and 19.4% and 88.5% among Italian women with normal and abnormal cytology respectively. HPV infection was detected in 56.1% of Southern and Eastern European, 62.5% of Central and South American, 55.5% of West African, and 73.3% of Southern Asian women with normal cervix. Among the 140 HPV-positive migrants, a total of 28 mucosal HPV genotypes were identified of which 11 types (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, and 58), epidemiological classified as carcinogenic to humans (group 1), accounted for 73.4% of all infections. As expected, HPV16 was the most common viral type in all groups with frequency rates ranging from 12.5% in African to 30.1% in Eastern and Southern European women. In conclusion, the estimated prevalence of HPV infection among migrant women is very high, probably reflecting either lifestyle or high incidence of HPV in their country of origin. The implementation of vaccination strategies and cervical cancer surveillance are critical for women in this risk group.