Persistant human papillomavirus infection and smoking increase risk of failure of treatment of cervical intraepithelial neoplasia (CIN)

Abstract

Women with abnormal smears have an increased risk of developing cervical cancer. During the 8 years following conservative treatment of cervical intraepithelial neoplasia (CIN), their risk of invasive cervical cancer is about 5 times greater than that of the general population. Human papillomavirus (HPV) has been associated with the natural history of both CIN and cervical cancer. To date, there have been no published reports on the predictive value of HPV testing in the treatment outcome of CIN. A prospective, multi-center, cohort study was conducted on women in the Northwest of England who were attending for treatment of CIN. They were asked to complete a questionnaire, which included a detailed smoking history. Pre-and post-treatment HPV testing was performed on cervical biopsies and cervical swab, being taken with the first follow-up smear at 6 months. A nested case-control analysis was performed, cases being de- Carcinoma of the cervix is the leading cause of female cancer mortality in the developing world. 1 In developed countries, the implementation of cervical screening has had a significant impact on the incidence of cervical cancer because of the early detection of the pre-invasive disease and its effective treatment. During the 8 years following treatment of cervical intraepithelial neoplasia (CIN) the risk of invasive cervical cancer for these women remains about 5 times greater than that of the general population of women. 2 Treatment failure of CIN has been found to be associated with the size of the lesion, partially involved excision margins and the degree of CIN. 3-5 Current methods of treatment have all been associated with success rates of 90 -95%. 3,4 All treated women require follow-up to detect residual or recurrent disease, and the ability to distinguish high and low risk women for treatment failure would allow more rational protocols to be developed.Human papillomavirus (HPV) infection, particularly types 16 and 18, has been associated with the occurrence of CIN. 6 Among women with low-grade cervical smear abnormalities, high-risk HPV types are associated with high-grade underlying CIN. [7][8][9] In screened women, persistence of HPV infection has been found to be associated with a greatly increased risk of developing CIN. 10 It has been suggested that, since HPV is detected in many asymptomatic low grade CIN lesions and only a minority of persistent HPV infections progress to cancer, additional factors are necessary if malignant change is to occur. 11 One possible factor may be the exposure to chemical carcinogens such as those present in cigarette smoke. Smoking appears to be the most important factor affecting the progress of CIN after HPV infection. 12 Epidemiological evidence has already implicated cigarette smoking as a possible contributing factor to the development of cervical neoplasia. 13 Smokers have a 4-fold increased risk of developing cervical cancer compared to non-smokers. 14 Smoking is associated with the occurrence of high grade of CIN in the presence of mild dyskaryosis...

Routine follow-up intervals in patients with high-grade squamous intraepithelial lesions (HSIL) and free excision margins can safely be increased in the first two years after Large Loop Excision of the Transformation Zone (LLETZ)

“…Persistent post-treatment high-risk human papillomavirus (hr-HPV) is a risk factor for subsequent SIL [15,16]. A meta-analysis of Zielinski et al showed that the status of excision margins, posttreatment cytology, post-treatment hr-HPV or combinations had a negative predictive value of 91-99%, the positive predictive values of these parameters were 25-51% [17].…”

Human Papillomavirus Testing Following Loop Electrosurgical Excision Procedure Identifies Women at Risk for Posttreatment Cervical Intraepithelial Neoplasia Grade 2 or 3 Disease

“…However, even women with clear margins following excision are at risk for disease recurrence (8). Carcinogenic human papillomavirus (HPV), the causative agent of cervical cancer and its precursor lesions, is present in up to one third of women following LEEP and is associated with disease recurrence (5,6,(9)(10)(11). Therefore, HPV testing may serve as a surveillance tool for identifying women at high risk of recurrence.…”

Clinical Performance of Hybrid Capture 2 Human Papillomavirus Testing for Recurrent High-Grade Cervical/Vaginal Intraepithelial Neoplasm in Patients With an ASC-US Papanicolaou Test Result During Long-Term Posttherapy Follow-up Monitoring

“…In short-term follow-up, rates of recurrent/ residual CIN/VAIN 2þ ranged from 7% to 17.9%. [18][19][20][25][26][27] There are very few reports of long-term follow-up monitoring studies. In a large cohort of patients treated for CIN 3, Melnikow et al 5 reported a rate of recurrent/ residual CIN 2þ of 14%.…”