Journal of Clinical Virology 31 (2004) 270–274
Factors associated with HPV persistence after treatment for high-grade
cervical intra-epithelial neoplasia with large loop excision of the
transformation zone (LLETZ)
Lu´ ıs Otávio Zanatta Sarian, Sophie Françoise Mauricette Derchain
*
, Denise da Rocha Pitta,
Sirlei Siani Morais, Silvia Helena Rabelo-Santos
Obstetrics and Gynecology Department, Universidade Estadual de Campinas, UNICAMP, Campinas, Brazil
Received in revised form 1 May 2004; accepted 18 May 2004
Abstract
Background and objective: Human Papillomavirus (HPV) persistence after high-grade cervical intra-epithelial neoplasia (CIN) removal
may be associated with residual lesions or risk of disease recurrence. Knowledge regarding the factors associated with HPV persistence
following CIN treatment is still limited. The main purpose of this longitudinal study was to assess the association between characteristics of
the patients and their cervical lesions with high-risk HPV-type persistence, detected by commercially available Hybrid Capture II (HC II),
after CIN 2 and 3 treatment with large loop excision of the transformation zone (LLETZ). Study design: For this cohort study, a total of 94
women submitted to LLETZ between March 2001 and September 2002 were included. Only women with at least one follow-up visit at 6 or
12 months and confirmed CIN 2 or 3 in the cone specimen were considered. In each visit women answered to a questionnaire and undertook
Pap smear and HC II specimens collection. McNemar’s, chi-square and Fisher tests were used for univariate analysis. Generalized Estimating
Equations (GEE) were used for multivariate analysis. All calculations were performed within 95% confidence intervals (95% CI). Results:
Histological evaluation showed 12 (13%) women with CIN, 2 and 82 (87%) with CIN 3 and conization margins were compromised in 27
(29%) cases. Eighty-seven (92%) women showed positive HC II tests prior to LLETZ. Of women initially HPV negative, none had a positive
HC II during follow-up. The proportion of positive HPV tests was reduced from 92% to 20%(P < 0.01) at the first visit and to 22% (P <
0.01) at the second visit after LLETZ. Multivariate analysis showed that smoking and age above 35 years (irrespective of margin status) were
strongly associated with positive HPV during follow-up. Conclusion: HPV persistence following LLETZ was associated with smoking and
with the interaction between age and conization margins.
© 2004 Published by Elsevier B.V.
Keywords: Human Papillomavirus; Clearance; Age; Smoking; Hybrid capture II
1. Introduction
Compelling data showed that conservative treatments
for cervical intra-epithelial neoplasia (CIN) are effec-
tive in preventing the development of cervical carcinoma
(Duggan et al., 1999). Large loop excision of the transfor-
mation zone (LLETZ) has been accepted by the medical
community as the mainstay technique for high-grade CIN
removal. LLETZ has some advantages over other conserva-
*
Corresponding author. Present address: Rua Antonio Hossri no 629 –
CEP: 13083-370, Campinas, São Paulo, Brazil. Tel.: +55 19 3788 9302;
fax: +55 19 3788 9302.
E-mail address: derchain@supernet.com.br (S.F.M. Derchain).
tive treatments: it can be performed under local anesthesia
and in an office setting, preserve fertility and has simi-
lar CIN cure rates when compared to other conservative
treatments (Duggan et al., 1999; Eduardo et al., 1996;
Flannelly et al., 1997; Paraskevaidis et al., 2001). Never-
theless, patients who underwent LLETZ must be followed
closely because 5–30% of them may present CIN recur-
rences in up to 30 months after the procedure (Holowaty
et al., 1999).
Current follow-up after LLETZ usually comprises at least
biannual consultations with gynecological examination,
colpocytology (Pap test) and colposcopy. However, Pap test
has some inherent flaws, the most important of which are
the negative results even in the presence of histologically
1386-6532/$ – see front matter © 2004 Published by Elsevier B.V.
doi:10.1016/j.jcv.2004.05.012