Traditional population-based cervical screening programs, based on cytology, have successfully reduced the burden of cervical cancer. Nevertheless limitations remain and new screening methods are emerging. Despite vaccination against the 2 most oncogenic types (HPV 16/18), cervical cancer screening will have to continue as an essential public health strategy. As the acquisition of an HR-HPV infection is critical in the progression to (pre-)cancerous cervical lesions, recent research has focused on HR-HPV detection. The sensitivity of HPV testing in primary and secondary prevention outweighs that of cytology, at the cost of slightly lower specificity. Although most of the HR-HPV infections are cleared after conization, new evidence from numerous studies encourages the implementation of HR-HPV testing and genotyping to improve posttreatment surveillance. An HR-HPV test 6 months after conization is a promising useful clinical marker to detect persistence and prevent progression. This review highlights the clinical role of HPV testing in primary and secondary cervical cancer screening. 1. Burden of Cervical Cancer Cervical cancer (CC) is the third most common cancer among women worldwide (15%) and the second most common in developing countries [1]. It is estimated by the World Health Organization that every year approximately 530000 women are diagnosed with CC worldwide and 275000 women die from the disease [2]. More than 80% of the global burden occurs in developing countries, where it accounts for 13% of all female cancers. In western countries, the incidence and mortality of CC have declined substantially over the past decades, whereas in developing countries there is a slight increase in mortality (Figure 1). This is probably due to the lack of screening and the greater impact of infectious cofactors in the latter regions [3]. Age-adjusted incidence rates vary from about 10 per 100000 per year in many industrialized countries to more than 40100000 in some developing countries. More than 88% of deaths occur in low-income countries and it is predicted to increase to 91.5% by 2030 [4]. Figure 1: Estimated cervical cancer incidence worldwide in 2008. GLOBOCAN 2008, International Agency for Research on Cancer. The red and dark highlighted areas have the highest incidence rates. Infection with a high-risk HPV (HR-HPV) genotype has been identified as the most important etiologic risk factor for the development of CC and is the necessary step in carcinogenesis. The median age of diagnosis is 45 years, and there are two major histological types; 85% of all cases
References
[1]
P. Appleby, V. Beral, A. B. de González et al., “Cervical cancer and hormonal contraceptives: collaborative reanalysis of individual data for 16,573 women with cervical cancer and 35,509 women without cervical cancer from 24 epidemiological studies,” The Lancet, vol. 370, no. 9599, pp. 1609–1621, 2007.
[2]
M. Arbyn, X. Castellsagué, S. de Sanjosé et al., “Worldwide burden of cervical cancer in 2008,” Annals of Oncology, vol. 22, no. 12, Article ID mdr015, pp. 2675–2686, 2011.
[3]
W. A. Tjalma, T. R. van Waes, L. E. van den Eeden, and J. J. Bogers, “Role of human papillomavirus in the carcinogenesis of squamous cell carcinoma and adenocarcinoma of the cervix,” Best Practice & Research Clinical Obstetrics & Gynaecology, vol. 19, no. 4, pp. 469–483, 2005.
[4]
U. Saxena, C. Sauvaget, and R. Sankaranarayanan, “Evidence-based screening, early diagnosis and treatment strategy of cervical cancer for national policy in low-resource countries: example of India,” Asian Pacific Journal of Cancer Prevention, vol. 13, no. 4, pp. 1699–1703, 2012.
[5]
S. M. Garland, “Can cervical cancer be eradicated by prophylactic HPV vaccination? Challenges to vaccine implementation,” Indian Journal of Medical Research, vol. 130, no. 3, pp. 311–321, 2009.
[6]
C. B. J. Woodman, S. I. Collins, and L. S. Young, “The natural history of cervical HPV infection: unresolved issues,” Nature Reviews Cancer, vol. 7, no. 1, pp. 11–22, 2007.
[7]
S. de Sanjose, W. G. Quint, L. Alemany, et al., “Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study,” The Lancet Oncology, vol. 11, no. 11, pp. 1048–1056, 2010.
[8]
S. K. Kj？r, K. Frederiksen, C. Munk, and T. Iftner, “Long-term absolute risk of cervical intraepithelial neoplasia grade 3 or worse following human papillomavirus infection: role of persistence,” Journal of the National Cancer Institute, vol. 102, no. 19, pp. 1478–1488, 2010.
[9]
J. C. Roa, P. Garcia, J. Gomez et al., “HPV genotyping from invasive cervical cancer in Chile,” International Journal of Gynecology & Obstetrics, vol. 105, no. 2, pp. 150–153, 2009.
[10]
D. Saslow, D. Solomon, H. W. Lawson et al., “American cancer society, American society for colposcopy and cervical pathology, and American society for clinical pathology screening guidelines for the prevention and early detection of cervical cancer,” CA: A Cancer Journal for Clinicians, vol. 62, no. 3, pp. 147–172, 2012.
[11]
J. T. Cox, P. E. Castle, C. M. Behrens, A. Sharma, T. C. Wright Jr, and J. Cuzick, “Comparison of cervical cancer screening strategies incorporating different combinations of cytology, HPV testing, and genotyping for HPV 16/18: results from the ATHENA HPV study,” The American Journal of Obstetrics & Gynecology, vol. 208, no. 3, pp. 184.e1–184.e11, 2013.
[12]
B. Andrae, T. M. Andersson, P. C. Lambert et al., “Screening and cervical cancer cure: population based cohort study,” The British Medical Journal, vol. 344, no. 7849, article e900, 2012.
[13]
M. R. McCredie, K. J. Sharples, C. Paul et al., “Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: a retrospective cohort study,” The Lancet Oncology, vol. 9, no. 5, pp. 425–434, 2008.
[14]
M. Arbyn, P. Sasieni, C. J. Meijer, C. Clavel, G. Koliopoulos, and J. Dillner, “Chapter 9: clinical applications of HPV testing: a summary of meta-analyses,” Vaccine, vol. 24, supplement 3, pp. S3/78–S3/89, 2006.
[15]
G. D. Zielinski, A. G. Bais, T. J. Helmerhorst et al., “HPV testing and monitoring of women after treatment of CIN 3: review of the literature and meta-analysis,” Obstetrical & Gynecological Survey, vol. 59, no. 7, pp. 543–553, 2004.
[16]
M. Kocken, M. H. Uijterwaal, A. L. de Vries et al., “High-risk human papillomavirus testing versus cytology in predicting post-treatment disease in women treated for high-grade cervical disease: a systematic review and meta-analysis,” Gynecologic Oncology, vol. 125, no. 2, pp. 500–507, 2012.
[17]
S. Cecchini, F. Carozzi, M. Confortini, M. Zappa, and S. Ciatto, “Persistent human papilloma virus infection as an indicator of risk of recurrence of high-grade cervical intraepithelial neoplasia treated by the loop electrosurgical excision procedure,” Tumori, vol. 90, no. 2, pp. 225–228, 2004.
[18]
L. O. Sarian, S. F. Derchain, L. A. Andrade, J. Tambascia, S. S. Morais, and K. J. Syrj？nen, “HPV DNA test and Pap smear in detection of residual and recurrent disease following loop electrosurgical excision procedure of high-grade cervical intraepithelial neoplasia,” Gynecologic Oncology, vol. 94, no. 1, pp. 181–186, 2004.
[19]
I. Alonso, A. Torné, L. M. Puig-Tintoré et al., “Pre- and post-conization high-risk HPV testing predicts residual/recurrent disease in patients treated for CIN 2-3,” Gynecologic Oncology, vol. 103, no. 2, pp. 631–636, 2006.
[20]
J. Verguts, B. Bronselaer, G. Donders et al., “Prediction of recurrence after treatment for high-grade cervical intraepithelial neoplasia: the role of human papillomavirus testing and age at conisation,” BJOG: An International Journal of Obstetrics & Gynaecology, vol. 113, no. 11, pp. 1303–1307, 2006.
[21]
O. C. Smart, P. Sykes, H. Macnab, and L. Jennings, “Testing for high risk human papilloma virus in the initial follow-up of women treated for high-grade squamous intraepithelial lesions,” Australian and New Zealand Journal of Obstetrics and Gynaecology, vol. 50, no. 2, pp. 164–167, 2010.
[22]
J. Jones, A. Saleem, N. Rai et al., “Human Papillomavirus genotype testing combined with cytology as a “test of cure” post treatment: the importance of a persistent viral infection,” Journal of Clinical Virology, vol. 52, no. 2, pp. 88–92, 2011.
[23]
M. Kocken, T. J. Helmerhorst, J. Berkhof et al., “Risk of recurrent high-grade cervical intraepithelial neoplasia after successful treatment: a long-term multi-cohort study,” The Lancet Oncology, vol. 12, no. 5, pp. 441–450, 2011.
[24]
J. Heymans, I. H. Benoy, W. Poppe, and C. E. Depuydt, “Type-specific HPV geno-typing improves detection of recurrent high-grade cervical neoplasia after conisation,” International Journal of Cancer, vol. 129, no. 4, pp. 903–909, 2011.
[25]
A. R. Kreimer, R. S. Guido, D. Solomon et al., “Human papillomavirus testing following loop electrosurgical excision procedure identifies women at risk for posttreatment cervical intraepithelial neoplasia grade 2 or 3 disease,” Cancer Epidemiology Biomarkers and Prevention, vol. 15, no. 5, pp. 908–914, 2006.
[26]
M. G？k, V. M. H. Coupé, J. Berkhof et al., “HPV16 and increased risk of recurrence after treatment for CIN,” Gynecologic Oncology, vol. 104, no. 2, pp. 273–275, 2007.
