The development of invasive carcinoma following treatment by loop excision biopsy is considered a failure of treatment

In this study we evaluate human papillomavirus deoxyribonucleic acid testing after conization in predicting residual disease. In 56 of 58 patients (96.6%), HPV DNAs were detected in their primary cervical lesions prior to conization. Up to August 2000, all of the 58 patients have been followed with a mean follow-up period of 31.8 months (range: 12 to 73 months).

After treatment, HPV DNA was persistently detected in 11 (19.6%) but negative in 45 (80.4%) of 56 HPV DNA-positive patients. Five of 11 persistently HPV DNA-positive patients (45.5%) developed CIN recurrence, while none of 45 persistently HPV DNA-negative patients did.

This study confirms an exellent sensitivity and negative predictive value of HPV-DNA testing after conization in predicting residual cervical neoplasia

Signore, M.

Taccheri, I.

Villani, C.

Viola, E.

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Giorn. It. Ost. Gin. Vol. XXVII - n. 3Marzo 2005Residual disease and presence of human papillomavirusafter conizationI. TACCHERI*, M. SIGNORE, E. VIOLA, C. VILLANI70IntroductionLoop excision biopsy, also known as LLETZ(large loop excision of the transformation zone), isthe most common and popular method of treatmentof cervical intraepithelial neoplasia (CIN). Loop bio-psies are performed for both diagnostic and thera-peutic purposes. The histological evaluation of theloop excision biopsy specimen takes into account thegrade of CIN, the status of the margins of resection,the presence or absence of CIN in endocervicalcrypts, the presence or absence of invasion and cervi-cal glandular intraepithelial neoplasia, and any otherassociated pathology. The factors that have beenassociated with the failure of treatment or recurrenceof CIN include the presence of CIN at ectocervicaland endocervical margins of resection, involvementof endocervical glands, large CIN lesions, depth ofthe loop, high grade of CIN, and the age of thepatient. The development of invasive carcinoma fol-lowing treatment by loop excision biopsy is conside-red a failure of treatment. No biological markers ortechnologies useful to predict the natural history ofan individual CIN III are known. The probability ofprogression is considered greater with the persistenceof high-risk human papillomavirus (HPV) infectionand age. In this study we evaluate the human papillo-mavirus deoxyribonucleic acid testing  after coniza-tion with reference to the prediction of residual disea-se.Materials and methodsThe present study deals with 58 patients who wereUniversity of PerugiaGynaecologic and Obstetric School(Director: C. Villani)Hospital of Frosinone*Department of Obstetrics and GynaecologyPervenuto in Redazione: ottobre 2004Copyright 2005, CIC  Edizioni Internazionali, RomaSUMMARY: Residual disease and presence of human papillo-mavirus after conization.I. TACCHERI, M. SIGNORE, E. VIOLA, C. VILLANIThe development of invasive carcinoma following treatment by loop excisionbiopsy is considered a failure of treatmentIn this study we evaluate human papillomavirus deoxyribonucleic acidtesting  after conization in predicting residual disease.In 56 of 58 patients (96.6%), HPV DNAs were detected in their pri-mary cervical lesions prior to conization.Up to August 2000, all of the 58 patients have been followed with a meanfollow-up period of 31.8 months (range: 12 to 73 months). After treatment, HPV DNA was persistently detected in 11 (19.6%) butnegative in 45 (80.4%) of 56 HPV DNA-positive patients.Five of 11 persistently HPV DNA-positive patients (45.5%) developedCIN recurrence, while none of 45 persistently HPV DNA-negative patientsdid.This  study confirms an exellent sensitivity and negative predictive value ofHPV-DNA testing after conization in predicting residual cervical neoplasia.RIASSUNTO: Associazione tra presenza HPV e malattia resi-dua dopo conizzazione.I. TACCHERI, M. SIGNORE, E. VIOLA, C. VILLANILa  presenza di malattia residua dopo conizzazione è considerata un fal-limento del trattamento. In questo studio il test per la ricerca dell’HPV dopo conizzazione è statoutilizzato per predire  la presenza di malattia residua. In 56 delle 58 donne valutate (96,6%) è stata riscontrata la presenza diHPV nella lesione primaria,  prima della conizzazione. Fino all’agosto 2000, tutte le 58 donne sono state sottoposte  ad un perio-do di follow-up di 31,8 mesi (il range variava dai 12 ai 73 mesi).Dopo il trattamento, la ricerca dell’HPV-DNA  è risultata positiva  in11 casi (19,6%) e negativa in  45 delle 56 pazienti HPV-DNA positive.In 5 delle 11 pazienti (45,5%) positive per l’HPV-DNA si è sviluppa-ta una CIN, mentre in nessuna delle 45 pazienti risultate negative perl’HPV-DNA  è stata riscontrata una ricorrenza di malattia.Questo studio conferma l’alta sensibilità e il valore predittivo negativodell’HPV-DNA test dopo  conizzazione per predire la malattia residua.KEY WORDS:  Conization - HPV-DNA testing - Residual disease.Test per la ricerca all’HPV-DNA - Malattia residua.Residual disease  and presence of human papillomavirus after conization71tested for HPV DNA in the pre-treatment cervicallesions, out of the 74 who referred with CIN 3. Afterstandard therapeutic conization, patients were fol-lowed prospectively at the outpatient clinic. Our fol-low-up protocol was to follow patients without thera-peutic intervention as long as they developed norecurrence or recurrence of CIN 1 or 2; while patientswho experienced recurrence of CIN 3 were recom-mended reconization or hysterectomy. The polymera-se chain reaction for detecting HPV DNA wasperformed using fresh cell samples from the cervix. ResultsIn 56 out of the 58 patients (96.6%), HPV DNAswere detected in their primary cervical lesions prior toconization. With regard to the distribution of HPVtypes, HPV type 16 family (types 16, 31, and 35) wasidentified in 28 cases (50.0%), type 18 family (types18, 33 and 58) in 15 (26.8%), and type X in 18(32.1%).  Up to August 2000, all the 58 patients werefollowed-up for a mean period of 31.8 months (range:12 to 73 months). After treatment, HPV DNA waspersistently detected in 11 (19.6%) of the 56 HPVDNA-positive patients, but 45 (80.4%) of them werefound HPV DNA- negative. HPV DNA was notdetected in both HPV DNA-negative patients. Five ofthe 11 persistently HPV DNA-positive patients(45.5%) developed CIN recurrence, while none of the45 persistently HPV DNA-negative patients did.Thus, there was a significant difference between therecurrence rates of these two groups (P < 0.0001).Both patients who were initially HPV DNA-negativedeveloped no recurrence. Accordingly, the overallrecurrence following conservative treatment for CIN3 was 5 patients out of 58 (8.6%). Discussion and conclusionsPersistent HPV infection appears to be a clear riskfactor for persistent cervical intraepithelial neoplasia(CIN II) and type-specific persistence of high-riskHPV infection is a good predictor of the possibilityof developing high-grade lesions. HPV seems to be astronger predictor of persistent cervical abnormalitiesin women over 35. Certain types of HPV and persi-stent high loads of viral infection may be associatedwith increased risks of cervical neoplasia, but whetherthis justifies HPV DNA screening is still open todebate. HPV remains detectable longer than cervicalcytologic abnormalities, suggesting that HPV DNAtesting may be a more sensitive test for HPV infec-tion and that there may be a role for HPV- DNAtesting in women with ambiguous cytology results.Women treated for CIN2 or CIN3 remain at increa-sed risk of cervical cancer for at least 8 years in com-parison with the general population. Generally, cyto-logy and/or colposcopy have been used for post-treatment surveillance. HPV testing deserves investi-gation as another possible strategy to monitor theefficacy of the treatment. Several small studies haveshown that HPV DNA clearance is associated withlow risk of subsequent CIN after treatment, and per-sistent HPV positivity predicts increased risk of treat-ment failure. However, the possibility of vaginal reco-lonization with HPV or a new HPV infection withanother HPV type must be considered. This  studyconfirms the excellent sensitivity and negative predic-tive value of HPV-DNA testing after conization as faras the prediction of residual cervical neoplasia is con-cerned. Patients with persistent HPV infection afterconization for CIN 3 should be closely followedbecause they are at increased risk of developing disea-se recurrence.References1. ANDERSON M.C.: Invasive carcinoma of the cervix following localdestructive treatment for cervical intraepithelial neoplasia. Br. J. ObstetGynecol, 96: pag.1054-60, 1989. 2. SHERMAN M.E., SCHIFFMAN M., COX J.T.: Effects of age andhuman papilloma viral load on colposcopy triage: data from the randomizedAtypical Squamous Cells of Undetermined Significance/Low-GradeSquamous Intraepithelial Lesion Triage Study (ALTS). J. Natl. Cancer.Inst., 94: 102–7, 2002.3. 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Residual disease and presence of human papillomavirus after conization

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Residual disease and presence of human papillomavirus after conization

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