HPV prevalence and concordance in the cervix and oral cavity of pregnant women

OBJECTIVES: This investigation examined human papillomavirus (HPV) in pregnant women in order to characterize viral prevalence, types and concordance between infection in the cervix and in the oral cavity. METHODS: A total of 577 pregnant women seeking routine obstetric care were evaluated for HPV infection in their cervix during gestation and immediately before delivery, and in the oral cavity during gestation. Male partners present during the gestational clinic visit also provided a specimen from their oral cavity. HPV assessment was performed by PCR, dot blot hybridization and DNA sequencing. A sexual and health questionnaire was completed by the pregnant women. RESULTS: HPV prevalence in women was 29% in the cervix and 2.4% in the oral cavity. Among those with both gestational and delivery specimens, 35% were infected at least once and 20% had infection at both intervals. At delivery, 68% of infected women had an oncogenic HPV type in the cervix. There was no type-specific HPV concordance between the two cervical specimens, nor cervical and oral results in women, nor with cervical and oral findings between partners. CONCLUSION: The lack of association in HPV positivity and types between the cervix and oral cavity in these women suggests that self-inoculation is uncommon. This source of infection does not appear to be from oral contact with a current male partner, since there also was no concordance between partners. These results suggest either other modes of HPV transmission or differences in susceptibility to HPV infection or its clearance in the oral cavity and genital mucosa.     

Human papillomavirus (HPV) genotypes and HPV16 variants and risk of adenocarcinoma and squamous cell carcinoma of the cervix

Objective

Human papillomavirus (HPV) genotypes have been extensively studied in uterine cervix squamous cell carcinoma and HPV16 variants have been found to be associated with increased cancer risk, but few reports have been published on genotype distribution and HPV16 variant prevalence in adenocarcinoma tumors. The objective of this study was to analyze viral genotypes and HPV16 intratypic variants in cervical adenocarcinoma and squamous cell carcinoma of Italian women.

Methods

A total of 39 invasive adenocarcinoma and 132 squamous cell carcinoma were reviewed and classified according to the modified WHO classification. HPV sequences were detected by nested PCR, using the broad spectrum consensus-primer pairs MY09/MY11 and the GP5+/GP6+ system, and genotyped by nucleotide sequence analysis. The HPV16-positive cases were amplified with E6-specific oligonucleotides and amplimers subjected to direct nucleotide sequence for variant identification.

Results

The prevalence rate of any HPV infection was 72% in adenocarcinoma, and 85% in cervical squamous cell carcinoma. Among the 140 HPV-positive cancer cases, a total of nine mucosal HPV genotypes (HPV16, 18, 31, 33, 35, 39, 45, 58, 82) epidemiologically classified as carcinogenic or probably carcinogenic viruses were identified. The HPV type 16 was the most common viral type representing 64% and 73% of all infections in adenocarcinoma and squamous cell carcinoma, respectively. The E6 nucleotide sequence analysis of HPV16 isolates allowed the identification of Asian American (AA) variants in 33% of adenocarcinoma and in 20% of squamous cell carcinoma suggesting their stronger association with cancer of glandular origin.

Conclusion

These results suggest that HPV16 has a high prevalence in both invasive adenocarcinoma and squamous cell carcinoma from Italian patients. Moreover this study confirms previous observations, summarized in a systematic review of the literature, on the increased cancer risk of HPV16 AA class in adenoglandular cancer, possibly related to their more oncogenic behavior compared to HPV16 European variants.     

Human papillomavirus (HPV) genotyping by HPV DNA chip in cervical cancer and precancerous lesions

OBJECTIVES: The human papillomavirus (HPV) is a well-known cause of cervical cancer. HPV tests are used as an adjunct test to decrease the false-negative rate of cytological screening. However, attempts are being made to replace the cytological screening with HPV tests. Therefore, this study was performed to examine the possibility of using HPV tests as screening test. MATERIALS AND METHODS: The results of the tests that were performed at the same time including the ThinPrep cytology, the high-risk group hybrid capture II (HC-II) test, the HPV DNA chip (HD-C) test, and a punch biopsy were compared in 400 women who were referred to us due to abnormal cytology or cervicogram. The accuracy of each test was then evaluated, and the type of virus was investigated using a HD-C test. RESULTS: The positive predictive values detected by the high-risk group HC-II test and HD-C test according to the histological diagnosis outcomes were 56.8 and 53.8%, respectively, for cervicitis; 91.5 and 91.5%, respectively, for cervical intraepithelial neoplasia I (CIN I); 88.1% and 81.0%, respectively, for CIN II; 88.6 and 84.2%, respectively, for CIN III, and 92.5 and 88.7%, respectively, for cancer (in 53 patients). The most prevalent types of HPV according to the HPV tests were types 16, 58, 18, and 52 in which type 16 was detected in the more advanced lesions. The sensitivity was 88.4% for the ThinPrep cytology, 89.9% for the HC-II for the high-risk group, and 86.2% for the HD-C test. CONCLUSION: These results suggest the possibility of using the HC-II and HD-C tests as screening tests, which have a similar sensitivity as the ThinPrep cytology. Nonetheless, randomized controlled trials will be needed before the actual application of the HPV tests as screening tests. Despite the fact that the importance of HPV type 16 in cancer development was confirmed, the prevalence of types 58 and 52 were relatively high compared with those found in other studies, showing a need for further studies on this subject. These HPV types need to be considered in vaccine development.     

Detection of HPV genotypes in cervical lesions by the HPV DNA Chip and sequencing

OBJECTIVE: A newly introduced HPV detection technique in cervical lesion, the HPV DNA Chip test, contains 24 HPV probes and has the advantage of being able to detect 24 HPV types at once. We performed HPV DNA sequencing and compared the results with that of the HPV DNA Chip for evaluation of the accuracy of the DNA Chip test. METHODS: The HPV DNA sequencing was performed in samples of 282 patients, where specific HPV type had been shown in HPV DNA Chip test. The sixteen cases where multiple HPV types had been found in HPV DNA Chip test were included in 282 cases. The sequencing was also performed in HPV-other type samples of 95 patients, where positive in HPV-PCR, but specific HPV type had not been found. RESULTS: In 257 cases (91.1%) of 282 cases, the HPV types of the HPV DNA sequencing test were in agreement with types of the HPV DNA Chip. In 16 cases (5.7%), the sequencing types were different from the types of HPV DNA Chip. But, in 9 of 16 cases, types in HPV DNA sequencing were absent types in HPV DNA Chip test. The interpretation of HPV DNA sequencing was impossible in nine cases (3.2%). The HPV DNA sequencing test of 95 cases of HPV-other type showed that the sequencing types from 94 cases (98.9%) were absent types in HPV DNA Chip test. In sequencing test of HPV-other type, HPV-81 (20.0%), HPV-62 (14.7%), HPV-84 (13.7%), and HPV-61 (13.7%) were frequently detected. CONCLUSION: HPV DNA Chip is an accurate method for detecting the 24 HPV genotypes.     

Human papillomavirus (HPV) in an Icelandic population: correlation of HPV DNA to cyto- and histopathologic lesions and evaluation of treatment strategies

This study is based on 100 cases with cervical intra-epithelial neoplasia (CIN) smears referred for colposcopy and 200 controls with normal smears. The study analyses (a) the frequency of different grades of CIN and koilocytotic lesions among the cases based on cyto- and histopathologic findings; (b) the frequency of human papillomavirus (HPV) among the cases with Virapap/Viratype (V/V) in biopsies vs swabs and among the controls with V/V and polymerase chain reaction (PCR) in swabs; (c) the frequency of the HPV types according to the grade of CIN. Among the cases koilocytotic lesions were found in 98% of the biopsies and 27% of the smears. High-graded smears and high-risk viruses had at entry a positive predictive value (PPV) of 80% and 88% respectively and a sensitivity of 72% for histologically verified high-graded CIN lesions. Both tests combined increased the sensitivity to 88%. The false-negative rate of colposcopy was 3% and the undergraded rate of CIN I and unclassified CIN smears for histologically verified CIN II–III was 62%. Among the cases the rate of HPV positive tests increased with a higher CIN grade. Cytology and colposcopy are complementary for the diagnosis of CIN and the swabs and biopsies for the diagnosis of HPV. Among the cases the rate of HPV-positive tests with V/V was 62% (97% high-risk viruses) and among the controls 5.5% (78% high-risk viruses). Among the controls the frequency of HPV occurrence with PCR was 11.2% and decreased with older age. The therapeutic conclusions are that the high-graded CIN lesions should receive ablative treatment irrespective of HPV typing, whereas low-graded lesions with high-risk viruses should be treated or observed closely.     

Human papilloma virus infection in pregnant women with normal pap-smears, HPV oncogenity and risk factors

The process of carcinogenesis in both types of cervical carcinoma is dependent on the infection of oncogenic types of HPV. HPV infection could be diagnosed on the basis of whether or not the DNA virus in present. In pregnant women the latent-persistent infection easily changes into its active form. This process is related to changes in immunological response and concentration of the hormones. AIM: The main aim of the study was to evaluate the frequency of HPV infection in healthy pregnant women in second and third trimester of pregnancy and the presence of selected risk factors. MATERIAL AND METHODS: The study was conducted in 2005-2006 on hospitalized women in The Clinic of High Risk Pregnancy. The first group consisted of 180 pregnant women in 2nd trimester of pregnancy, the second comprised 220 pregnant women in the 3rd trimester. In all women the Pap-smears and diagnosis of DNA presence of high and low risk HPV from the border line of cervical epithelium were tested on the first day of the hospitalization. The PCR method using Human Papilloma Virus Typing Set was used. RESULTS: In 400 pregnant women the presence of HPV was found in 4.5%, type 16 was fund in 2.5%, type 18 in 1.7%. Combined infection 16 and 18 types was found in 0.2%. In 180 pregnant women in II trimester high risk HPV was found in 4.4%: 16 type was found in 2.8%, 18 type in 1.7%. In IlI trimester high risk HPV was found in 4.5%: 16 type was found in 2.3%, type 18 in 1.8%, combined 16 and 18 in 0.4%. Low risk HPV was found in 1.0%- type 6. In II trimester in 1.1%, In III trimester 0.9%. There were no differences between HPV infection rate in II and III trimester, pregnant women age, the gravity and HSV2 infection. The difference was found between high risk HPV infection and parity, cigarette smoking and oncological family history. CONCLUSION: Asymptomatic HPV infection has the same frequency in II and III trimester. High parity, cigarette smoking and oncological family history were connected with an increased rate of high risk HPV infection. All women in reproductive age should be checked for the HPV DNA.     

Human papillomavirus in the cervix and placenta

OBJECTIVE: To determine the prevalence and association of human papillomavirus (HPV) infection in the cervices and placentas of pregnant women. METHODS: Cervical samples were taken from 179 of 226 women who had placental biopsies because of abnormal ultrasound findings or were older than 35 years, to detect HPV infections with hybrid capture II tests. Polymerase chain reaction (PCR) was done on placental tissue of 147 of the 226 women to detect HPV DNA. RESULTS: We found 44 of 179 women (24.6%, 95% confidence interval 18.3, 31.0) to test positive for HPV in their cervices. Logistic regression analyses showed decreased prevalence of HPV infection with increased maternal age (P =.039). The HPV DNA E6 PCR from the villus tissue was negative in the 147 cases examined. However, a significant contingency coefficient between low-risk HPV infection and elevated risk of chromosome aberration was found (φ = V = 0.15, P =.050). CONCLUSION: The infection rate of 24.6% in women without clinical symptoms of HPV infection was high, but there seemed to be no virus transmission to the placenta in women with subclinical infections. Low-risk cervical HPV infection might be associated with a slightly higher risk of abnormal fetal karyotype.     

河北丰宁地区妇女人乳头瘤病毒感染及疫苗认知状况调查

目的调查河北省丰宁满族自治县妇女人乳头瘤病毒（HPV）感染及对宫颈癌、HPV和HPV疫苗的认知情况,并探讨宣教对其认知度的影响。方法对河北丰宁地区717例18~45岁妇女进行HPV相关知识的问卷调查及宣教,对其中647例妇女留取宫颈脱落细胞进行高危型HPV DNA检测。结果高危型HPV总检出率为16.07%（104/647）;14.78%（106/717）的妇女曾听说过HPV,HPV知晓率与年龄、婚姻情况、户口类型及教育程度有关（P〈0.05）;84.38%（605/717）的妇女从未行宫颈癌筛查,在112例行宫颈癌筛查的妇女中,末次筛查为巴氏涂片、宫颈液基细胞学和HPV检测者分别为16.07%（18/112）、39.29%（44/112）和8.04%（9/112）;宣教后HPV知晓率显著提高（P〈0.05）;15.76%（113/717）的妇女既往听说过HPV疫苗,75.59%（542/717）的妇女倾向于接种医疗机构提供的疫苗,24.41%（175/717）的妇女倾向于接种政府或医药公司提供的疫苗。结论河北丰宁地区妇女HPV现患率较高,对HPV及宫颈癌的认知率偏低,宣教后人群认知程度显著提高,因此公众教育可以显著提高人群对HPV疫苗相关知识的认知水平。     

Prevalence of HPV infection by cytologic diagnosis and HPV DNA extraction and prevalence of the HPV genotypes detected in urban Turkish women

Objective

To evaluate the prevalence of the different human papillomavirus (HPV) genotypes in women seen at 2 Marmara University Hospital gynecologic outpatient clinics in Istanbul, Turkey.

Methods

From May 1 through August 31, 2008, specimens were obtained from 500 women for cytologic evaluation by the split-sample method. HPV types were identified by PCR and hybridization using a microarray that identifies 35 types.

Results

The overall prevalence of HPV was 16.5%, multiple genotypes were found in 35.8% of the infected women, and 75% of the types were high risk; 79% of the infected women had negative cytologic results, 3.7% had ASCUS, 10% had LSIL, and 6% had HSIL; the highest infection rates were 36% for women aged 20 to 30 years and 35% for those aged 31 to 40 years; 65.2% of the infected women were university graduates; and 34% were single.

Conclusion

HPV infection involved numerous types, most of them high risk, even in women with negative cytology results. Further studies with larger groups will provide more information on HPV distribution in Turkey, which may guide the development of local vaccination programs.     

Human papillomavirus (HPV) infections as risk factors for cytological and histological abnormalities in baseline PAP smear-negative women followed-up for 2 years in the LAMS study

Objective

To assess the role of HPV as determinant of the incident cytological abnormalities (SIL) and cervical lesions (CIN) during a 24-month follow-up of baseline PAP smear-negative subgroup of women included in the Latin American Screening study (LAMS).

Study design

A group of 365 women with normal Pap smear and negative or positive high-risk Hybrid Capture II test were prospectively followed-up for 24 months at Campinas and São Paulo (Brazil). The incidence rate (IR) and risk ratio (RR and 95% CI) of developing cytological or histological abnormality during the follow-up was calculated for HPV-negative and HPV-positive women.

Results

During the 12-month follow-up, women HPV-positive at baseline had developed a significantly higher rate of incident LSIL (IR = 3.5%, RR = 1.4; 95% CI 1.1–1.7) and HSIL (IR = 0.7%, RR = 1.5; 95% CI 1.4–1.7) abnormality. For HSIL, the IR increased to 2.1% and the RR increased to 1.7 (95% CI 1.5–1.9) among those followed for 24 months. Similarly, women with positive HPV tests were at a higher risk of developing CIN 2–3 (IR = 2.6%, RR = 1.5; 95% CI 1.4–1.6) during the first 12 months of follow-up, and for those followed for 24 months, this RR increased further to 1.7 (95% CI 1.5–1.9) although the IR was 0.7%.

Conclusions

Oncogenic HPV infections comprise a significant risk factor for incident cervical abnormalities, and HPV test is a useful adjunct to cytology in detecting the high-risk patients among baseline PAP smear-negative women.     

Severe vitamin D deficiency among pregnant women and their newborns in Turkey

Objectives: Vitamin D deficiency is an important health problem in pregnant women and their infants in sunny countries. Low socio-economic status (LSES), covered dressing style, pregnancies in winter season and having dark skin are the major risk factors for vitamin D deficiency. The present study evaluated serum 25-hydroxyvitamin D3 [25(OH)D3] concentrations in pregnant women and in their newborns and determined the risk factors in LSES cities in Turkey.

Methods: Ninety-seven pregnant women and their newborns were included in the study between December 2012 and February 2013. All of the pregnant women had irregular follow-up or had received no antenatal care, were pregnant during summer, had presented to the hospital after 37 weeks of gestation (WG) and had received no vitamin D supplementation. A detailed history was obtained, which included mothers’ age, number of births and dressing sytle. Maternal and cord blood samples were taken to measure 25(OH)D3 levels.

Results: All of the pregnant women were predominantly LSES, had covered dressing style and none of them had received vit D3 supplementation during pregnancy. The mean serum 25(OH)D3 level and mean cord blood level of of 97 mothers were 4.97?±?3.27?ng/ml and 4.29?±?2.44?ng/ml, respectively. There was a strong positive correlation between maternal serum and umbilical cord 25(OH)D3 levels (r: 0.735, p?<?0.05). Ninety-five mothers had serum 25(OH)D3 below 20?ng/ml and all cord blood serum 25(OH)D3 levels were below 20?ng/ml. Level of 25(OH)D3 was not correlated with mother age, WG or newborn weight. Serum 25(OH)D3 concentrations in primigravida and multigravida were 3.71?±?1.88 and 5.2?±?3.4?ng/ml, respectively, with a significant difference between them (p?<?0.05).

Conclusion: Severe vitamin D deficiency is common in reproductive women and their newborns in LSES cities of Turkey. Covered dressing style, not receiving any vitamin D supplementation and primigravida women are at greatest risk. Vitamin D supplementation campaigns which should cover pregnant women and the newborn to prevent maternal and perinatal vitamin D deficiency should be implemented especially in risk areas.     

Human papillomavirus DNA and mRNA positivity of the anal canal in women with lower genital tract HPV lesions: predictors and clinical implications

Objective

Women with HPV related pathology of the lower genital tract are at higher risk for AIN and anal cancer than the general population. A strategy to identify anal disease in these women has not been formulated. The aim of this study is to examine the feasibility of HPV related biomarker testing on anal smears, to identify the risk factors for anal HPV positivity and to provide information of the clinical implications of anal HPV infection in this population.

Methods

In women referred for colposcopy because of HPV related pathology of the lower genital tract (cervical cancer, CIN, VIN, warts) a detailed questionnaire, an anal smear and a cervical smear were taken. On each sample morphological cytology, flow cytometric evaluation of E6&7 mRNA, and HPV DNA detection and typing were performed. Women with a positive anal result were referred for high resolution anoscopy.

Results

So far 235 women have been included (mean age 34.3). HPV DNA, high-risk HPV DNA, high-risk mRNA was detected in 45%, 31% and 8% of the anal smears and in 56%, 39% and 25% of the cervical smears respectively. Absolute or partial concordance of the types between the cervix and the anus was seen in 74%. Positivity for mRNA was significantly lower in the anus than the cervix (8% vs 25%). Logistic regression analysis revealed risk factors for the presence of anal HPV DNA (> 3 lifetime sexual partners and presence of cervical HPV DNA), hr HPV DNA (presence of cervical hr HPV DNA), and hr mRNA (presence of cervical hr mRNA). Twelve months after LLETZ 53% of women were cervical HPV negative, but 25% of those were still HPV positive in the anus.

Conclusions

HPV infection of the anus is common in this group and is interlinked with the cervical infection. Anal HPV E6&7 mRNA expression is less common than in the cervix. Possible clinical implications of anal infection could be the development of AIN and recurrence of CIN after treatment due to cervical reinfection from the anal reservoir. The use of HPV biomarkers is feasible in anal smears, although especially DNA testing as triage method for referral to anoscopy is probably inappropriate due to high positivity rate.     

Human papillomavirus (HPV) type distribution in cervical carcinoma, low-grade, and high-grade squamous intraepithelial lesions in Venezuelan women

Objective

Cervical cancer is an important cause of mortality among women in developing countries, especially in the Latin America and Caribbean (LAC) region. Infection with high-risk (HR) human papillomavirus (HPV) has been identified as the primary cause of cervical cancer. The aim of this study was to determine the frequency of HR-HPV genotypes in low-grade and high-grade squamous intraepithelial lesions (LSIL, HSIL) and cervical carcinoma (CC) among Venezuelan women.

Materials and methods

Subjects with histopathological diagnosis of LSIL, HSIL, and CC (LSIL = 200; HSIL = 100; CC = 150) were enrolled in the study after obtaining informed consent. Biopsy samples of these subjects were analyzed to determine the lesion type. HPV detection and typing was done using polymerase chain reaction (PCR) and reverse hybridization. HPV type specific prevalence was determined in subjects with single and multiple infections.

Results

HPV DNA was detected in 68%, 95%, and 98.7% of LSIL, HSIL, and CC cases, respectively. HR-HPV and low-risk oncogenic HPV (LR-HPV) was observed in 66.9%/11.8% of LSIL cases, 87.3%/3.2% of HSIL cases, and 91.2%/0.7% of CC cases. HPV types -16/-18 (65%) were the most common high-risk HPV types observed, followed by types -52, -33, -45, and -31.

Conclusion

Cervical cancer burden in Venezuelan women is substantial. HPV types -16/-18 were the most common types prevalent among Venezuelan women followed by types -52, -33, -45, and − 31 (prevalence, ~ 90.1%). The results of this study provide baseline information on the HPV type distribution, which may facilitate the development of a cervical cancer prevention and control program in Venezuela.     

Human papillomavirus vaccination in the resourced and resource-constrained world

Human papillomavirus has been established as the causal agent for cervical cancer. The identification of a clear cause presents an unparalleled opportunity for cancer control. As such, the development of prophylactic human papillomavirus vaccines has been rightly hailed as one of the significant scientific triumphs of the past 20 years. This story of scientific triumph over disease, however, is not yet complete. The fruit of scientific labour must be delivered to the people in order to fulfil the underlying intent of the research (i.e. to prevent cancer and save lives). The success of a vaccination programme, however, does not depend on the biological efficacy of the vaccine alone. Various other local factors, such as poverty, gender inequality, cultural traditions, or religious beliefs, can significantly constrain the success of any vaccination programme. In this chapter, we provide an overview of how the human papillomavirus vaccine works and its global uptake, as well as, how variations in local contexts can affect the successful implementation of a vaccination programme. Other factors besides vaccine costs also need serious attention. With better understanding of such factors, policy makers and medical health professionals will be better equipped to make informed decisions to maximise the potential benefits of the human papillomavirus vaccines for the most number of people in individual countries.