OUTLOOK HPV

HPV: THE GLOBAL BURDEN

H PV CO MES I N M A N Y F O M S
Tens of di erent papillomavirus types infect humans, but only a handful are harmful. Mapping HPV types by genus (right) reveals that certain species o en cause simlar warts and lesions, with most of the HPV types that cause cancer coming from the same species. However, shared pathology doesnt always indicate close family ties; HPV types 1, 2 and 4, which all cause cause common skin warts, are distant relations.

Human papillomavirus (HPV) has become synonymous with cervical cancer, but its actual footprint is much bigger, by James Mitchell Crow.
49 7 07 5 3 04

6 5 76 92 9

7 06 90 89 02 83 4 84 86 87

05

80

7 37

2 92

6 72 62 8 57 2 27

Lines divide species

63 4

4 74

Genus

7 40
43 9

20 2 3

38 0 0 22

6 35
52 6

7 33

4 20 2 9 25 05 8 99 2 47 36 5 8 2 4 93 2 4 98

Non-human papillomaviruses (>80 types)

2 42 78 7 0 94 28 3 29 77 45 8 97 70 73 54 3 39 68 58 34 59 8

CERVICAL CANCER BY HPV TYPE

OTHE (3.4%) 59 ( .3%)

H OW HPV CA N LE A D TO CA N C E
Although HPV infections are common, 90% of cervical infections are cleared within 2 years. If infection persists, abnormal cells can begin to appear. Only if these cervical cells cross the basal membrane and spread into the tissues beneth does the condition become cervical cancer.
Normal Exposure CIN1 Transient infection CIN2 CIN3 Persistent infection Cancer

Progression Normal cervix Clearance Productive infection Regression Precursor lesion Invasive lesion

A few abnormally sized and oddly shaped cells on the surface of the cervix is classi ed as Cervical Intraepithelial Neoplasia 1 (CIN1), a low grade lesion that typically disappears within a few months without treatment. A large number of precancerous cells on the surface of the cervix that are distinctly di erent from normal cells is classi ed as CIN3. High-grade CIN3 lesions are still reversible spontaneously or through treatment.

Low-grade lesions High-grade lesions Cervical cancer Type-speci c HPV prevalence in women (%)

6 ( 8.5%) 8 (5.8%) OTHE

6 (44. %) 8 (7%) OTHE

6 (54.4%) 8 ( 6.5%) OTHE

Infection with certain HPV subtypes is more likely to lead to cancer than others. HPV types 16 and 18 make up only 2.7% and 1.1% of initial cervical infections respectively, but together account for 70% of cervical cancer cases.

S 2 | NAT U R E | VO L 4 8 8 | 3 0 AUG U S T 2 0 1 2

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66

63

03 08

09

6 (54.4%) 8 ( 6.5%) 58 (5. %) 33 (4.7%) 45 (4.4%) 3 (3.6%) 52 (3.4%) 35 ( .9%) 39 ( .3%)

HPV genera: -papillomaviruses infect mucosal surfaces and skin, -, -, - and -papillomaviruses only skin.

5 95 4 6 50 2 0 48 66

, , , ,

Most common high-risk subtypes linked to cancer Subtypes responsible for over 90% of genital warts Subtypes mainly responsible for common skin warts

26 6 95 82 3 05

8 23

35

HPV OUTLOOK

INFECT I O N AT ES A ND CA N C E CAS ES
Cervical HPV infection rates vary around the world, as does the number of infected women who go on to develop cervical cancer.
Overall prevalence in healthy women Most prevalent HPV types

EUROPE 6.6%

NORTHERN 3.8% AMERICA

39 (0.9%)

6 (3.5%) 53 ( . %) 52 ( .0%) 8 ( .0%) 6 (4.0%) 3 ( .9%) 8 ( .8%) 53 ( .5%) 58 ( .2%)

6 (2.3%) 8 (0.7%) 3 (0.6%) 33 (0.4%) 58 (0.4%)

ASIA 8.3%

6 (2.6%) 52 ( .2%)

58 ( .0%) 8 (0.8%) 56 (0.8%)

PARKIN DM, BRAY F. VACCINE. 2006;24 (SUPPL 3):S11S25. J. DILLNER ET AL., BMJ 2008; 377: A1754, WHO/ICO INFORMATION CENTRE ON HPV AND CERVICAL CANCER. SANJOSE DE, S. LANCET INFECT. DIS. 7 453459 (2007).

CENTRAL AMERICA & MEXICO

20.5%

AFRICA

SOUTH AMERICA

22.9%
6 (3.3%) 58 ( .4%) 8 ( .2%) 3 ( .3%) 58 ( .6%)

6 (2.7%) 52 ( .8%) 8 ( .6%)

Worldwide HPV prevalence in healthy women.

HPV AN D C ANC E

Although the overwhelming majority of cancers caused by HPV infection are of the cervix, infection with the virus can also lead to cancers in other parts of the body.
Total cancers Cancer attributable to HPV Attributable to HPV 16/18

0% 0%
0

4.3%
3 (0.9%) 45 (0.9%)

Governmentreported age-standardized cervical cancer incidence rate per 100,000 women per year.

56.3 30 20.3 12.9 6.9 No data

A number of risk factors are known to increase the risk of HPV infection progressing to cervical cancer, including HIV coinfection, smoking, younger mothers, high number of children.

T H E F UT U E OF H P V S C EENI NG
HPV tests are proving more e ective than traditional cytology screens at catching early-stage infections that progress to high-risk lesions.
Cytology HPV test Cytology / HPV test

500,000
60,000 50,000 40,000 30,000 20,000 10,000 0

ENLARGED
Incidence of CIN3+ per 10,000 women following negative test result

100

400,000 Total number of cancer cases

80

300,000

60

200,000

40

Oropharynx

Vagina

Anus

Penis

Part of the human body

100,000

ENLARGED
Cervix Mouth Oropharynx Vagina Anus Penis

20

0 0 12 24 36 48 60 72 Part of the human body Time since testing (months)

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