Human papillomavirus infections in early childhood – Immune response and disease outcome in The Finnish Family HPV Study Cohort

Human papillomavirus (HPV) infects epithelial cells on the skin or mucosa. It is an important risk factor for cervical cancer and head and neck cancers. A child may acquire HPV infection during childhood, even before birth. However, our knowledge of HPV prevalence and HPV‐specific immunity in children is limited. In the present study, the prevalence of oral HPV infection among 331 infants was elucidated. Further, HPV 16‐specific cell‐mediated immune response was studied in 56 children, aged from 10 to 16 years, who either 1) had a mother with a cervical intraepithelial neoplasia or 2) had a HPV‐egative mother or 3) had HPV DNA detected in placenta and/or cord blood or 4) had persistent oral HPV or 5) remained constantly HPV‐negative during a six‐year follow‐up period. HPV was detected in 18% of the 331 infants up to two months of age: HPV 16 was the most prevalent genotype, followed by HPV 6, 11, 18, 33, and 66. The HPV genotypes and the serum antibodies for HPV capsid protein L1 were concordant between mother and newborn. HPV DNA in the placenta was the most powerful predictor (OR=14.0;95%CI,3.7‐52.2;P=.0001) of oral HPV in the newborn. A majority of 56 children showed HPV 16‐specific proliferative T cell response. The cytokine production of T cells indicated a more predominant Th2 response in children who had had HPV‐positive placenta and/or cord blood. These results support the view that an infected mother transmits HPV to her newborn. The placenta is a substantive route for HPV transmission and might also play a role in the development of HPV‐specific immunity. HPV 16‐specific proliferative T cell response was common in children, indicating a prior HPV 16 infection.Ihmisen papilloomavirusinfektiot varhaislapsuudessa ja niihin liittyvä immuunivaste – HUPA‐kohorttitutkimus Papilloomavirus (HPV, human papillomavirus) infektoi ihon ja limakalvojen epiteelisoluja. HPV‐infektio on tärkein kohdunkaulan syövän ja merkittävä pään‐ ja kaulan alueiden syöpien riskitekijä. HPV‐infektion voi saada jo varhaislapsuudessa tai jopa ennen syntymää. Lasten HPV‐infektioista ja niihin liittyvästä immunologiasta tiedetään kuitenkin hyvin vähän. Tämä väitöskirjatutkimus on osa Finnish Family HPV Study‐seurantatutkimusta. Työn tarkoituksena oli selvittää HPV‐infektioiden ja veren seerumin HPV L1 ‐kuoriproteiinille spesifisten vasta‐aineiden esiintymistä 331 vastasyntyneellä kahden kuukauden ikään saakka sekä niiden mahdollista yhteyttä äidin HPV‐infektioihin. Lisäksi työssä selvitettiin HPV 16 ‐spesifisen soluvälitteisen immuunivasteen esiintymistä lapsilla 10–16 vuoden iässä. Kuuden vuoden seurannan tulosten perusteella tutkimukseen valittiin 56 lasta seuraavasti: 1) lapset, joiden äideillä oli löydetty syövän esiastemuutos kohdunkaulan limakalvolta, 2) lapset, joiden äidit olivat olleet HPV‐negatiivisia, 3) lapset, joiden istukka ja/tai napaverinäyte oli syntymän hetkellä HPV‐positiivinen, 4) lapset, joilla oli löydetty persistoiva suun HPV‐infektio ja 5) lapset, joiden suunäytteet olivat olleet aina HPV‐negatiivisia. Suun limakalvon HPV‐infektio todettiin ensimmäisen kahden elinkuukauden aikana 18 %:lla 331 vastasyntyneestä. Yleisimmin esiintyi HPV 16 yksin tai muiden genotyyppien kanssa. Seuraavaksi yleisimpiä olivat HPV ‐genotyypit 6, 11, 18, 33 ja 66. Lapselta ja äidiltä osoitetut HPV‐genotyypit olivat yhtenevät. Lisäksi lapselta löydettiin yhden kuukauden iässä HPV‐spesifisiä vasta‐aineita samoille HPV ‐genotyypeille kuin äidiltä ennen synnytystä. Istukan HPV‐positiivisuus oli voimakkain ennustekijä vastasyntyneen suun HPV‐positiivisuudelle. HPV 16‐spesifinen T‐solujen proliferaatiovaste löydettiin suurimmalla osalla tutkituista 56 lapsesta. T‐solujen sytokiinieritys ilmensi voimakkaampaa Th2‐soluvastetta niillä lapsilla, joiden istukka tai napaveri oli todettu HPV ‐positiiviseksi. Tulokset osoittavat HPV‐infektion todennäköisesti siirtyvän infektoituneesta äidistä vastasyntyneeseen. Istukalla on tärkeä osuus virustartunnassa ja todennäköisesti myös HPV‐spesifisen immuniteetin muodostumisessa. Suurimmalla osalla tutkituista 56 lapsesta todettiin HPV 16 ‐proteiineja tunnistavia immunologisia muistisoluja, mikä viittaa aikaisempaan HPV 16 ‐infektioonSiirretty Doriast

Peripheral Blood T-lymphocyte Phenotypes in Mother-Child Pairs Stratified by the Maternal HPV Status : Persistent HPV16 vs. HPV-Negative: A Case-Control Study

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Interferon-gamma and IL-5 associated cell-mediated immune responses to HPV16 E2 and E6 distinguish between persistent oral HPV16 infections and noninfected mucosa

Objectives: Natural history of human papillomavirus (HPV) infection in the head and neck region is poorly understood, and their impact on collective HPV-specific immunity is not known. Materials and methods: In this study, we have performed a systematic analysis of HPV16-specific cell-mediated immunity (CMI) in 21 women with known oral and genital HPV DNA status and HPV serology (Ab) based on 6-year follow-up data. These women being a subgroup from the Finnish Family HPV Study were recalled for blood sampling to be tested for their CMI-responses to HPV16 E2, E6, and E7 peptides. Results: The results showed that HPV16 E2-specific lymphocyte proliferation was more prevalent in women who tested HPV16 DNA negative in oral mucosa and were either HPV16 seropositive or negative than in HPV16 DNA+/Ab+ women (p = 0.046 and p = 0.035). In addition, the HPV16 DNA-/Ab- women most often displayed E6-specific proliferation (p = 0.020). Proportional cytokine profiles indicated that oral HPV16-negative women were characterized by prominent IFN-gamma and IL-5 secretion not found in women with persisting oral HPV16 (p = 0.014 and p = 0.040, respectively). Conclusions: Our results indicate that the naturally arising immune response induced by oral HPV infections displays a mixed Th1/Th2/Th17 cytokine profile while women with persisting oral HPV16 might have an impaired HPV16-specific CMI, shifted partly toward a Th2 profile, similarly as seen earlier among patients with high-grade genital HPV lesions. Thus, the lack of HPV 16 E2 and E6 specific T memory cells and Th2 cytokines might also predispose women for persistent oral HPV16 infection which might be related to the risk of cancer.Peer reviewe

Interferon-gamma and IL-5 associated cell-mediated immune responses to HPV16 E2 and E6 distinguish between persistent oral HPV16 infections and noninfected mucosa

Objectives: Natural history of human papillomavirus (HPV) infection in the head and neck region is poorly understood, and their impact on collective HPV-specific immunity is not known.Materials and methods: In this study, we have performed a systematic analysis of HPV16-specific cell-mediated immunity (CMI) in 21 women with known oral and genital HPV DNA status and HPV serology (Ab) based on 6-year follow-up data. These women being a subgroup from the Finnish Family HPV Study were recalled for blood sampling to be tested for their CMI-responses to HPV16 E2, E6, and E7 peptides.Results: The results showed that HPV16 E2-specific lymphocyte proliferation was more prevalent in women who tested HPV16 DNA negative in oral mucosa and were either HPV16 seropositive or negative than in HPV16 DNA+/Ab+ women (p = 0.046 and p = 0.035). In addition, the HPV16 DNA-/Ab- women most often displayed E6-specific proliferation (p = 0.020). Proportional cytokine profiles indicated that oral HPV16-negative women were characterized by prominent IFN-gamma and IL-5 secretion not found in women with persisting oral HPV16 (p = 0.014 and p = 0.040, respectively).Conclusions: Our results indicate that the naturally arising immune response induced by oral HPV infections displays a mixed Th1/Th2/Th17 cytokine profile while women with persisting oral HPV16 might have an impaired HPV16-specific CMI, shifted partly toward a Th2 profile, similarly as seen earlier among patients with high-grade genital HPV lesions. Thus, the lack of HPV 16 E2 and E6 specific T memory cells and Th2 cytokines might also predispose women for persistent oral HPV16 infection which might be related to the risk of cancer.</div

Boletín de Segovia: Número 3 - 1889 enero 4

Copia digital. Madrid : Ministerio de Cultura. Subdirección General de Coordinación Bibliotecaria, 200

Nuorten liikuntakäyttäytyminen Suomessa : LIITU-tutkimuksen tuloksia 2020

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