The causal role of human papillomavirus infections in cervical cancer has been documented beyond reasonable doubt. The association is present in virtually all cervical cancer cases worldwide. It is the right time for medical societies and public health regulators to consider this evidence and to define its preventive and clinical implications. A comprehensive review of key studies and results is presented.

https://jcp.bmj.com/content/jclinpath/55/4/244.full.pdf

The causal relation between human papillomavirus and cervical cancer

The objective of this study was to describe the prevalence of Klinefelter syndrome (KS) prenatally and postnatally in Denmark and determine the influence of maternal age. All chromosomal examinations in Denmark are registered in the Danish Cytogenetic Central Registry. Individuals with KS diagnosed prenatally or postnatally were extracted from the registry with information about age at the time of diagnosis and mother's age. In the period 1970-2000, 76,526 prenatal examinations on male fetuses resulted in the diagnosis of 163 fetuses with KS karyotype, corresponding to a prevalence of 213 per 100,000 male fetuses. Standardization according to maternal age resulted in a prevalence of 153 per 100,000 males. Postnatally, 696 males of 2,480,858 live born were diagnosed with KS, corresponding to a prevalence among adult men of approximately 40 per 100,000. Less than 10% of the expected number was diagnosed before puberty. Advanced maternal age had a significant impact on the prevalence. KS is severely underdiagnosed in Denmark. Only approximately one fourth of adult males with KS are diagnosed. There is a marked delay in diagnosis of the syndrome. A delay in treatment with testosterone may lead to decreased muscle and bone mass with subsequent risk of osteoporosis.

/pdf/prenatal-and-postnatal-prevalence-of-klinefelter-syndrome-a-4ao3o1xjyi.pdf

Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study.

pReVIously ClAssIfIed by IARC As “CARCInogenIC to humAns (gRoup 1)” And wAs deVeloped by sIx sepARAte woRkIng gRoups: phARmACeutICAls; bIologICAl Agents; ARsenIC, metAls, fIbRes, And dusts; RAdIAtIon; peRsonAl hAbIts And IndooR CombustIons; ChemICAl Agents And RelAted oCCupAtIons. thIs Volume 100f CoVeRs ChemICAl Agents And RelAted oCCupAtIons, speCIfICAlly 4-AmInobIphenyl, benzIdIne, dyes metAbolIzed to benzIdIne, 4,4’-methylenebIs(2-ChloRoAnIlIne), 2-nAphthylAmIne, oRtho-toluIdIne, AuRAmIne And AuRAmIne pRoduCtIon, mAgentA And mAgentA pRoduCtIon, benzo[A]pyRene, CoAl gAsIfICAtIon, oCCupAtIonAl exposuRes duRIng CoAl-tAR dIstIllAtIon, CoAl-tAR pItCh, Coke pRoduCtIon, untReAted oR mIldly tReAted mIneRAl oIls, shAle oIls, soot, As found In oCCupAtIonAl exposuRe of ChImney-sweeps, oCCupAtIonAl exposuRes duRIng AlumInIum pRoduCtIon, AflAtoxIns, benzene, bIs(ChloRomethyl)etheR And ChloRomethyl methyl etheR, 1,3-butAdIene, 2,3,7,8-tetRAChloRodIbenzo-pARA-dIoxIn, 2,3,4,7,8-pentAChloRodIbenzofuRAn, And 3,3’,4,4’,5-pentAChloRobIphenyl, ethylene oxIde, foRmAldehyde, sulfuR mustARd, VInyl ChloRIde, IsopRopyl AlCohol mAnufACtuRe by the stRong-ACId pRoCess, mIsts fRom stRong InoRgAnIC ACIds, oCCupAtIonAl exposuRes duRIng IRon And steel foundIng, oCCupAtIonAl exposuRe As A pAInteR, oCCupAtIonAl exposuRes In the RubbeR mAnufACtuRIng IndustRy. beCAuse the sCope of Volume 100 Is so bRoAd, Its monogRAphs ARe foCused on key InfoRmAtIon. eACh monogRAph pResents A desCRIptIon of A CARCInogenIC Agent And how people ARe exposed, CRItICAl oVeRVIews of the epIdemIologICAl studIes And AnImAl CAnCeR bIoAssAys, And A ConCIse ReVIew of the Agent’s toxICokInetICs, plAusIble meChAnIsms of CARCInogenesIs, And potentIAlly susCeptIble populAtIons, And lIfe-stAges. detAIls of the desIgn And Results of IndIVIduAl epIdemIologICAl studIes And AnImAl CAnCeR bIoAssAys ARe summARIzed In tAbles. shoRt tAbles thAt hIghlIght key Results ARe pRInted In Volume 100, And moRe extensIVe tAbles thAt InClude All studIes AppeAR on the monogRAphs pRogRAmme websIte (http://monogRAphs.IARC.fR). It Is hoped thAt thIs Volume, by CompIlIng the knowledge ACCumulAted thRough seVeRAl deCAdes of CAnCeR ReseARCh, wIll stImulAte CAnCeR pReVentIon ACtIVItIes woRldwIde, And wIll be A VAlued ResouRCe foR futuRe ReseARCh to IdentIfy otheR Agents suspeCted of CAusIng CAnCeR In humAns. D es ig n by A ude la d es m ot s

iArc monogrAphs on the evAluAtion oF cArcinogenic risks to humAns

Age-specific prevalence of infection with human papillomavirus in females: a global review.

HIV-positive women have a high prevalence of human papillomavirus (HPV) infection and are infected with a broader range of HPV types than HIV-negative women. It is not known to what extent these different types are associated with highgrade squamous intraepithelial lesions (HSIL) and cancer. Meta-analysis of HPV type-specific prevalence among HIV-positive women stratified by geographical region and by cervical cytology: normal atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesions (ASCUS/ LSIL) or HSIL. In 20 studies 5578 HIV-positive women were identified largely from North America but also Africa Asia Europe and South/Central America. For 3230 with no cytological abnormalities prevalence was 36.3% for any HPV and 11.9% for multiple HPV types. The six most common high-risk HPV types were 16 (4.5%) 58 (3.6%) 18 (3.1%) 52 (2.8%) 31 (2.0%) and 33 (2.0%). HPV16 was also the most common type in 2053 HIV-positive women with ASCUS/LSIL and 295 with HSIL. Those with HSIL were significantly less likely to be infected with HPV16 (odds ratio 0.6; 95% confidence interval 0.4-0.7) than the general female population with HSIL. In contrast HIV-positive women with HSIL were significantly more likely to be infected with HPV types 11 18 33 51 52 53 58 and 61 and with multiple HPV types. The proportion of HIV-positive women with HPV16 rose with increasing severity of cervical lesions. Nevertheless HPV16 remained underrepresented in HIV-positive women with HSIL who showed a higher proportion of other HPV types and multiple types compared with the general female population with HSIL. (authors)

http://www.hu.ufsc.br/projeto_hpv/Human%20papillomavirus%20types%20among%20women%20infected.pdf

Human papillomavirus types among women infected with HIV: A meta-analysis

The clinical application of quantitative fluorescent polymerase chain reaction (QF-PCR) for rapid prenatal detection of chromosome aneuploidies has been limited in most studies to the detection of autosomal trisomies. Recently it has been shown that a newly identified highly polymorphic marker, termed X22, which maps to the Xq/Yq pseudoautosomal region of the sex chromosomes, used together with the X-linked short tandem repeat (STR) HPRT, allows the accurate detection of gonosome aneuploidies. We have developed a rapid assay, which includes these STR markers together with a sequence of the amelogenin region of the sex chromosomes and selected highly polymorphic autosomal STR. Two more X chromosome markers, as yet not used in previous QF-PCR applications, were also included in the assay. The molecular test was then used in a clinical trial on 551 uncultured amniotic fluid samples, allowing the assessment of copy number for chromosomes X, Y and 21 in 100% of cases. In the course of this study, two fetuses with Turner's syndrome and one with Klinefelter's syndrome were identified along with 17 autosomal trisomies. The assay proved to be so efficient and reliable that in most aneuploidy cases, in which ultrasound findings were in agreement with the molecular result, therapeutical interventions were possible without waiting for the result of cytogenetic analysis.

Clinical application of multiplex quantitative fluorescent polymerase chain reaction (QF-PCR) for the rapid prenatal detection of common chromosome aneuploidies

Background Despite being deliberately targeted to common chromosome aneuploidies, the rapid quantitative fluorescent polymerase chain reaction (QF-PCR) tests can detect the majority of chromosome abnormalities in prenatal diagnosis. The main advantages of this assay are low cost, speed and automation allowing large-scale application. Methods We developed a QF-PCR test that was applied on 43 000 clinical samples reporting results in 24 h. Most common indications were biochemical risk (32%) and advanced maternal age (30%). Samples were also tested by cytogenetic analysis and the results compared. Results Aneuploidies involving chromosomes 21, 18, 13, X and Y were detected with 100% specificity. Several cases of partial trisomies and mosaicism were also identified. Overall 95% of clinically relevant abnormalities were readily detected and termination of affected pregnancies could be performed without waiting for the cytogenetic results. Conclusions Our study supports the possibility of reducing the load of prenatal cytogenetic tests if the pregnancies are carefully monitored by non-invasive screening. In case of abnormal QF-PCR results, medical action can be taken within few hours from sampling. In cases of negative QF-PCR results, cytogenetic analyses might only be performed for fetuses with ultrasound abnormalities. In countries where large-scale cytogenetic tests are not available, QF-PCR may be used as the only prenatal diagnostic procedure.

Rapid prenatal diagnosis of common chromosome aneuploidies by QF-PCR, results of 9 years of clinical experience

The concordance of the prevalence of human papillomavirus (HPV) DNA in 188 sex workers in five different locations was investigated. HPV was found in 43.6% of the women, and its prevalence at genital sites was similar. Prevalence was highest among women aged 20 years or younger but declined thereafter in specimens from all anogenital sites.

https://jcm.asm.org/content/jcm/42/3/1330.full.pdf

Concordance of Prevalence of Human Papillomavirus DNA in Anogenital and Oral Infections in a High-Risk Population

Fundamento
La identificacion de grupos de alto riesgo para infeccion genital por el virus del papi-loma humano puede contribuir a la prevencion precoz del carcinoma de cuello uterino. El estudio fue disenado para estimar la prevalencia y factores determinantes de infeccion por el virus del papiloma humano cervical y el riesgo de cancer de cuello uterino en reclusas en regimen preventivo.
Pacientes y metodo
Se estudiaron 157 mujeres a su ingreso en el Centro Penitenciario de Mujeres de Barcelona. Se les realizaron visita ginecologica, entrevista estructurada, exfoliado cervical y muestra de sangre para la deteccion del virus de la inmunodeficiencia humana (VIH) y virus de la hepatitis B y C. La infeccion por el virus del papiloma humano se determino me-diante reaccion en cadena de la polimerasa.
Resultados
La prevalencia de ADN del virus del papiloma humano fue del 46%. El 38,2% de las mujeres afirmaron haber practicado la prostitucion y el 64,3% ser usuarias de drogas por via parenteral (UDVP). El 56,1% fueron seropositivas para el VIH. La citologia cervical revelo que 19 mujeres (12,1%) presentaban alteraciones escamosas de significado desconocido y 28 (17,7%), lesiones escamosas intraepiteliales (todos los grados). La infeccion del virus del papiloma humano se asocio a UDVP durante mas de 10 anos (odds ratio de la prevalencia [POR] = 2,9) y a seropositividad por VIH (POR = 4,7). El aumento de riesgo para lesiones escamosas in-traepiteliales asociado a VIH se explica por la presencia de virus del papiloma humano. Las mujeres positivas para el VIH con recuento bajo de CD4 podrian tener mayor riesgo de presentar lesiones escamosas intraepiteliales.
Conclusiones
Las mujeres con VIH constituyen un grupo de alto riesgo para el virus del papiloma humano y, consecuentemente, para el desarrollo de lesiones preneoplasicas del cervix. Se recomienda un control ginecologico frecuente en las mujeres positivas para el VIH y el virus del papiloma humano.

Infección por los virus del papiloma humano y de la inmunodeficiencia humana como factores de riesgo para el cáncer de cuello uterino en mujeres reclusas

Objective: Detection of high-risk human papillomavirus types (HPV) infection is an important tool in the screening of cervical cancer and triage of cytological abnormalities. The different techniques for detection of this cancer need to be contrasted and validated for use in population screening. Material and Methods: Cervical cell samples were collected from 166 women attending a dermatology clinic in Oviedo (Spain). We evaluated the performance of three different assays for VPH detection. The methods utilized were 1) In-house PCR-EIA using L1 consensus primers MY09/ MY11, 2) A PCR-reverse line blot hybridization (PCR-LBH) that uses L1 consensus PGMY primers. 3) Hybrid Capture 2. All assays were performed blinded. The kappa statistic was used to test for global agreement between assay pairs. Results: HPV DNA was detected in 24,7%, 25,3% and 29,5% of the women, respective to the assay. The overall agreement between the in-house PCR, PCR-LBH and HC2 was (73.5%) with all kappa values between assay pairs exceeding 0.56 (p<0.001). Conclusion: The three HPV assays were equally accurate in estimating high-risk HPV prevalence and HPV-related lesions. The method for HPV detection must be decided depending on the goals of the search (screening, follow-up or molecular studies).

/pdf/evaluacion-de-las-tecnicas-de-deteccion-del-vph-en-los-3fld7l1uv4.pdf

M. Paz Cañadas

Papers

Clinical application of multiplex quantitative fluorescent polymerase chain reaction (QF-PCR) for the rapid prenatal detection of common chromosome aneuploidies

Rapid prenatal diagnosis of common chromosome aneuploidies by QF-PCR, results of 9 years of clinical experience

Concordance of Prevalence of Human Papillomavirus DNA in Anogenital and Oral Infections in a High-Risk Population

Infección por los virus del papiloma humano y de la inmunodeficiencia humana como factores de riesgo para el cáncer de cuello uterino en mujeres reclusas

Evaluación de las técnicas de detección del VPH en los programas de cribado para cáncer de cuello uterino