Human papillomavirus (HPV) is the most common sexually transmitted agent worldwide. Persistent HPV infection causes cervical cancer and is responsible for a fraction of other anogenital, head and neck cancer. The risk of neoplastic progression differs markedly by membership risk group, persistence and coexistence of different genotypes. In this cohort analysis of genotype-specific HPV testing, results from 4,373 women and 128 men (age range: 14-89) with a total of 6,898 tissue samples received in ASST Lodi between February 2007 and December 2019 were considered. HPV-DNA was assayed by INNOLiPA Genotyping extra II to determine single and multiple infections among more than 32 genotypes. The prevalence of HPV infection was 61% (2761/4501) in the patients recruited. Specifically, the most frequent HPV type observed was HPV-52 occurring in 23.21% of the cases, followed by HPV-16 [20.96%, CI 95% (17.19%-24.73%)], HPV-53 [18.48%, CI 95% (14.66%-22.31%)], HPV-31 [14.51%, CI 95% (10.59%-18.43%)], HPV-54 [14.18%, CI 95% (10.25%-18.11%)], and HPV-66 [14.09%, CI 95% (10.16%-18.02%)]. The analysis of the incidence of infections stratified by diagnostic level showed the presence and persistence of single and multiple HPV infections involved in the progression of cell abnormalities. The evidence of viral genotypes found in morphologically normal diagnoses underlined the frequent discrepancy between molecular and cytological results. This observation confirmed the importance to extend HPV molecular testing as exclusive means for primary screening. A statistical evaluation was performed through a two-way tetrachoric matrix for observed viral frequency to analyze the viral associations between two or more genotypes. It was highlighted that some HPV types established strongly co-infections with many different types (p≤0.005), underlining that cooperative relationships could exist among them. On the contrary, the infrequent relationships established between two genotypes could underline competitive behaviors or poor viral cooperative efficiency (p≥0.05). The high prevalence of the HPV-53, HPV-54 and HPV-66 genotypes could be important to reassess their carcinogenic classification to high-risk type. The data obtained on the prevalence and distribution of HPV genotypes were used to evaluate and summarize the epidemiological characteristics and models of HPV infection. Further studies will be needed in order to evaluate the distribution dynamics of HPV types shift post-vaccine in the population.
Il papillomavirus umano (HPV) è l'agente virale a trasmissione sessuale più comune in tutto il mondo. La persistenza dell’infezione è correlata all’insorgenza di neoplasia cervicale ed è responsabile di una frazione di altri tumori anogenitali, della testa e del collo. Il rischio di progressione neoplastica differisce notevolmente per classe associativa di rischio virale, per persistenza e per coesistenza dei diversi genotipi virali. In questa analisi di coorte basata sulla genotipizzazione degli HPV, sono stati considerati i risultati di 4.373 donne e 128 uomini (fascia di età: 14-89) per un totale di 6.898 campioni reclutati presso ASST Lodi tra febbraio 2007 e dicembre 2019. Il genotipo virale è stato tipizzato con il kit INNOLiPA Genotyping II Extra, utilizzato per l’identificazione delle infezioni singole e multiple di più di 32 genotipi differenti. È stata riscontrata la presenza d’infezione da HPV nel 61% dei pazienti reclutati. La valutazione epidemiologica ha confermato che il genotipo a maggior prevalenza è risultato essere l’HPV-52 presente nel 23.21% dei casi, seguito da HPV-16 [20.96%, CI 95% (17.19%-24.73%)], HPV-53 [18.48%, CI 95% (14.66%-22.31%)], HPV-31 [14.51%, CI 95% (10.59%-18.43%)], HPV-54 [14.18%, CI 95% (10.25%-18.11%)] e HPV-66 [14.09%, CI 95% (10.16%-18.02%)]. L’analisi di incidenza delle infezioni stratificate per grado diagnostico ha evidenziato la presenza e persistenza di infezioni singole e multiple potenzialmente coinvolte nella progressione del differenziamento cellulare. L’evidenza di genotipi virali riscontrata in diagnosi di normalità morfologica cellulare sottolinea la frequente discrepanza tra risultati molecolari e citologici. Questa osservazione conferma l’importanza dell’estensione del test molecolare di genotipizzazione a test di I livello diagnostico. È stata eseguita una valutazione statistica con matrice tetracorica a doppio ingresso per frequenza virale osservata per valutare lo stato di associazione virale tra genotipi. Si evidenzia come alcuni genotipi virali stabiliscano forti co-infezioni associative con più genotipi virali (p≤0,005) a conferma che potrebbero esistere dinamiche di sinergia nell’evoluzione dell’infezione. Al contrario, relazioni tra genotipi poco frequenti (p≥0,05) potrebbero evidenziare comportamenti competitivi o di scarsa efficienza cooperativa virale. L’elevata prevalenza riscontrata dei genotipi HPV-53, HPV-54 e HPV-66 potrebbe essere importante per rivalutare la loro cancerogenicità a virus ad alto rischio. I dati ottenuti sulla prevalenza e sulla distribuzione dei genotipi dell'HPV sono stati utilizzati per valutare e sintetizzare le caratteristiche epidemiologiche e i modelli di infezione da HPV. Studi ulteriori saranno necessari per valutare la variazione della distribuzione dei genotipi in seguito al vaccino HPV nella popolazione.
Prevalenza e distribuzione genotipica del Papillomavirus umano nella provincia di Lodi.
POMERO, VERONICA
2019/2020
Abstract
Human papillomavirus (HPV) is the most common sexually transmitted agent worldwide. Persistent HPV infection causes cervical cancer and is responsible for a fraction of other anogenital, head and neck cancer. The risk of neoplastic progression differs markedly by membership risk group, persistence and coexistence of different genotypes. In this cohort analysis of genotype-specific HPV testing, results from 4,373 women and 128 men (age range: 14-89) with a total of 6,898 tissue samples received in ASST Lodi between February 2007 and December 2019 were considered. HPV-DNA was assayed by INNOLiPA Genotyping extra II to determine single and multiple infections among more than 32 genotypes. The prevalence of HPV infection was 61% (2761/4501) in the patients recruited. Specifically, the most frequent HPV type observed was HPV-52 occurring in 23.21% of the cases, followed by HPV-16 [20.96%, CI 95% (17.19%-24.73%)], HPV-53 [18.48%, CI 95% (14.66%-22.31%)], HPV-31 [14.51%, CI 95% (10.59%-18.43%)], HPV-54 [14.18%, CI 95% (10.25%-18.11%)], and HPV-66 [14.09%, CI 95% (10.16%-18.02%)]. The analysis of the incidence of infections stratified by diagnostic level showed the presence and persistence of single and multiple HPV infections involved in the progression of cell abnormalities. The evidence of viral genotypes found in morphologically normal diagnoses underlined the frequent discrepancy between molecular and cytological results. This observation confirmed the importance to extend HPV molecular testing as exclusive means for primary screening. A statistical evaluation was performed through a two-way tetrachoric matrix for observed viral frequency to analyze the viral associations between two or more genotypes. It was highlighted that some HPV types established strongly co-infections with many different types (p≤0.005), underlining that cooperative relationships could exist among them. On the contrary, the infrequent relationships established between two genotypes could underline competitive behaviors or poor viral cooperative efficiency (p≥0.05). The high prevalence of the HPV-53, HPV-54 and HPV-66 genotypes could be important to reassess their carcinogenic classification to high-risk type. The data obtained on the prevalence and distribution of HPV genotypes were used to evaluate and summarize the epidemiological characteristics and models of HPV infection. Further studies will be needed in order to evaluate the distribution dynamics of HPV types shift post-vaccine in the population.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
Per maggiori informazioni e per verifiche sull'eventuale disponibilità del file scrivere a: unitesi@unipv.it.
https://hdl.handle.net/20.500.14239/21549