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Human papillomavirus PCR direct sequencing study of cervical precancerous lesions in Quebec children
  1. Luc L Oligny1,
  2. Juan Carlos Feoli-Fonseca1,
  3. Pierre Brochu1,
  4. Pierre Simard1,
  5. Sarah Falconi2,
  6. Wagner V Yotov3
  1. 1Département de Pathologie, Hôpital Ste-Justine, Montréal, Québec, Canada
  2. 2Programme de Biologie Moléculaire, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada
  3. 3Département de Pathologie, Hôpital Ste-Justine, Montréal, Québec, Canada; Département de Pédiatrie, Université de Montréal; Département de Biochimie, Université de Montréal, Québec, Canadawagner.yotov{at}umontreal.ca
  1. Dr Wagner Yotov, Hôpital Ste-Justine, Local 4731, 3175 Côte Ste-Catherine, Montréal, Québec H3T 1C5, Canadayotovw{at}ere.umontreal.ca

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Editor,—Similarly to adult pathology, human papillomavirus (HPV) infection is the most common sexually transmitted disease in adolescent girls, whose prevalence is 16% according to one US study.1 However, little or no HPV sequencing data from paediatric specimens are available. We used our two tier polymerase chain reaction (PCR) direct sequencing (PCR-DS) approach2 to study cervical biopsies from 44 adolescent Quebec girls (14–17 years old). They originated from various social and ethnic groups, as well as geographically distinct areas of Quebec. Written informed consent about the use of the specimens was obtained from the ethics committee of this institution. All biopsies were analysed for histological changes and presence of HPV specific DNA. Most of them (n = 36) were diagnosed as cervical intraepithelial neoplasia (CIN), seven as inflammatory changes, and one as “nil.” Among the 36 CIN, 33 (92%) tested HPV positive, including all CIN-II and CIN-III samples.

Sixteen HPV types were detected, four of them in more than two samples: HPV6 (n = 8), HPV16 (n = 7), HPV11 (n = 3), and HPV31 (n = 3). In the group of cervical biopsies from adolescent girls with CIN (n = 36, age 14–17), as well as in the larger control group of adult women (n = 487, age 18–72), the percentage of high risk HPV types increased, and the low risk HPV types decreased with the progression from low grade (CIN-I) to high grade (CIN-II and III) precancerous lesions. High risk HPV represented all but one HPV type (33/34) identified in CIN-III lesions from adult women, and all HPV types from 14–17 year old girls with CIN-III (fig 1).

The informative value of HPV testing in CIN, hence its clinical relevance, depends on whether there is an increase of the high risk HPV types in more advanced grades of precancerous lesions. The currently available data are conflicting. Some groups reported an increased frequency of high risk HPV from CIN-I to CIN-III, at the expense of the low risk HPV types,3 but others insisted that the high risk HPV rates in CIN-I, CIN-II, and CIN-III were similar.4 Our results indicate that the high risk HPV types are significantly increased from less than 50% in CIN-I to almost 100% in CIN-II and III, and this is valid for the adolescent and adult patients alike (fig 1). We hypothesise that the reasons for the discrepancies in the detection rate of various HPV types in CIN-I, II, and III may be due to the fact that some groups used the method of PCR with single pair of primers, MY09/11, which may be underrepresenting the most frequent low grade HPV types, up to a complete lack of detection for HPV6 and HPV11.5

This study indicates that a mass prophylactic HPV vaccine should be targeted at cohorts younger than 14–17 years, because at that age some girls already develop high grade precancerous cervical lesions with possible long term integration of the viral oncogenes in the host cell genome. We believe that a PCR direct sequencing approach to HPV testing will provide treating physicians and pathologists with precise HPV typing information, and may be used in vaccine design, application, and monitoring in children and adults.

Figure 1

Relative increase of the high risk HPV types in higher grade precancerous lesions, and decrease of low risk HPV types until their full disappearance in CIN-III lesions. Data similar for both age groups—children ≤17 year old and adults 18 years and above. The two groups differ in the number of HPV negative cases and the HPV types of unknown cancer risk.

Acknowledgments

Supported in part by the Canadian Institutes of Health Research (CIHR), grant number MOP-37874, Les Fonds de la recherche en santé du Québec (FRSQ), and La Fondation de l'Hôpital Ste-Justine (to WVY). WVY is a chercheur-boursier (scholar) of the FRSQ.

Contributors: LLO, PB, and PS performed the histological evaluation of the samples and signed the pathological reports; JCF-F and SF studied the HPV at DNA level; WVY provided supervision and wrote the manuscript with the help of the others.

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