Trip Answers

Question answered:29/01/08 Warning! this question is over two years old.

GPNotebook states:

 

“Genital warts are caused by different strains of human papilloma virus - especially HPV6.
…The mean incubation period is about 3 months. However, it is quite variable and may range from 3 weeks to 8 months.” [1]

 

A paper by Trottier and Franco on human papilloma virus and cervical cancer discusses the natural history of cervical cancer and notes in Figure 3:

 

“Figure 3. Natural History of Cervical Cancer Showing the Steps Amenable to Intervention Via HPV Vaccination and Screening

 

Women who have sex with HPV-infected individual
(within weeks to months some will develop)

 

HPV infection
(within weeks to months some will develop)

 

Persistent HPV infection with oncogenic types
(within months to years some will develop)

 

High-grade preinvasive cervical lesions
(within months to years some will develop)

 

Cervical cancer.”

 

It adds:

 

“HPV infects the stratified squamous epithelium and stimulates cellular proliferation. Infected cells display a wide range of alterations, from benign hyperplasia to dysplasia to invasive neoplasia. Provided that the latter step has not yet occurred, this process is reversible, including clearance of HPV infection and regression of precancer, which happens in many women who experience HPV infection.
The vast majority of HPV infections are transient, with only a small proportion becoming persistent. Several natural history studies have analyzed risks of progression in the continuum of preinvasive lesion stages. The Table [please see fulltext of article]  shows the average probabilities of regression and progression of CIN that were derived from a pooled analysis of studies published from 1950 to 1993. Differences between precursor and invasive lesions with respect to the age when incidence rates peak provide important clues to the duration of the preclinical phase of the natural history of cervical cancer. The incidence rate for CIS increases more steeply with age than for invasive cancer, reaching a peak at ages 25 to 29 years, and then declines gradually at older ages, whereas the incidence of invasive cancers levels off after ages 40 to 44. This leaves a gap between peak incidence rates for CIS and invasive cancer of approximately 15 years.” [2]

 

A 2007 guideline on the management of genital HPV also highlights the importance of the persistence of infection:

 

“Persistent infection is a marker for the development of CIN II and III. HPV 16 persists longer than other types, with an absolute risk of CIN III approaching 40% after five years’ persistence. The previous view that the “high risk” woman (for developing CIN II or III and cancer) was the woman with a history of an early coitarche, multiple sexual partners etc, must now be replaced by the concept that persistent HR HPV infection is the most important risk factor.

 

CIN III must be regarded as the surrogate endpoint for cancer. However, CIN II lesions may represent severe cytological changes associated with HPV infection that are destined to regress while others are destined to persist with risk of progression. The median age of women with CIN III is 27-30 years. However, intensive prospective follow-up of women in their early 20s has demonstrated the rapid development of CIN II and III, often within a few months of incident infection.38 Women with cervical screen detected invasive cancer are 10 years or more older than the median age of women presenting with CIN III.” [3]

 

In 1992, Koutsky et al presented the findings of a cohort study of cervical intraepithelial neoplasia grade 2 or 3 in relation to papillomavirus infection. The Medline abstract of this article reads:

 

“…METHODS. We studied prospectively a cohort of 241 women who presented for evaluation of sexually transmitted disease and had negative cervical cytologic tests. The women were followed every four months with cytologic and colposcopic examinations of the uterine cervix and tests for HPV DNA and other sexually transmitted diseases. RESULTS. Cervical intraepithelial neoplasia grade 2 or 3 was confirmed by biopsy in 28 women. On the basis of survival analysis, the cumulative incidence of cervical intraepithelial neoplasia at two years was 28 percent among women with a positive test for HPV and 3 percent among those without detectable HPV DNA. The risk was highest among those with HPV type 16 or 18 infection (adjusted relative risk as compared with that in women without HPV infection, 11; 95 percent confidence interval, 4.6 to 26; attributable risk, 52 percent).

 

All 24 cases of cervical intraepithelial neoplasia grade 2 or 3 among HPV-positive women were detected within 24 months after the first positive test for HPV. After adjustment for the presence of HPV infection, the development of cervical intraepithelial neoplasia was also associated with younger age at first intercourse, the presence of serum antibodies to Chlamydia trachomatis, the presence of serum antibodies to cytomegalovirus, and cervical infection with Neisseria gonorrhoeae…” [4]

 

References
1. GPNotebook. (http://www.gpnotebook.co.uk/simplepage.cfm?ID=-1811546105)
2. Trottier and Franco E. Human Papillomavirus and Cervical Cancer: Burden of Illness and Basis for Prevention. American Journal of Managed Care 2006; ;12:S462-S47). (http://www.ajmc.com/files/articlefiles/A172_dec06FrancoS462to472.pdf
3. Professional Advisory Board (PAB) of the Australia and New Zealand HPV Project. Guidelines for the Management of Genital HPV in Australia and New Zealand 5th Edition – 2007. (http://www.nzgg.org.nz/guidelines/0146/HPV_Guidelines_2007.pdf).
4. Koutsky LA, Holmes KK and Critchlow CW et al. A cohort study of the risk of cervical intraepithelial neoplasia grade 2 or 3 in relation to papillomavirus infection. N Engl J Med. 1992 Oct 29;327(18):1272-8. (http://www.hubmed.org/display.cgi?uids=1328880)

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